Alzhemier's Disease

Alzheimer’s & Dementia 13 (2017) 325–373

Alzheimer’s Association Report

2017 Alzheimer’s disease facts and figures

Alzheimer’s Association*

Abstract This article describes the public health impact of Alzheimer’s disease (AD), including incidence

*Email: sciencest

521-8007.

http://dx.doi.org/10.10

1552-5260

and prevalence, mortality rates, costs of care, and the overall impact on caregivers and society. The Special Report examines how the use of biomarkers may influence the AD diagnostic process and estimates of prevalence and incidence of the disease. An estimated 5.5 million Americans have Alzheimer’s dementia. By mid-century, the number of people living with Alzheimer’s dementia in the United States is projected to grow to 13.8 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops Alzheimer’s dementia every 66 seconds. By 2050, one new case of Alzheimer’s dementia is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year. In 2014, official death certificates recorded 93,541 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age �65 years. Between 2000 and 2014, deaths resulting from stroke, heart disease, and prostate cancer decreased 21%, 14%, and 9%, respectively, whereas deaths from AD increased 89%. The actual number of deaths to which AD contributes is likely much larger than the number of deaths from AD recorded on death certificates. In 2017, an estimated 700,000 Americans age �65 years will have AD when they die, and many of them will die because of the complications caused by AD. In 2016, more than 15 million family members and other unpaid caregivers provided an estimated 18.2 billion hours of care to people with Alzheimer’s or other dementias. This care is valued at more than $230 billion. Average per-person Medicare payments for services to beneficiaries age �65 years with Alzheimer’s or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2017 for health care, long-term care, and hospice services for people age �65 years with dementia are estimated to be $259 billion. In recent years, efforts to develop and validate AD biomarkers, including those detectable with brain imaging and in the blood and cerebrospinal fluid, have intensified. Such efforts could transform the practice of diagnosing AD from one that focuses on cognitive and functional symptoms to one that incorporates biomarkers. This new approach could promote diagnosis at an earlier stage of disease and lead to a more accurate understanding of AD prevalence and incidence.

Keywords: Alzheimer’s disease; Alzheimer’s dementia; Dementia; Diagnostic criteria; Risk factors; Prevalence; Incidence;

Mortality; Morbidity; Caregivers; Family caregiver; Spouse caregiver; Sandwich generation caregiver; Health

care costs; Health care expenditures; Long-term care costs; Medicare spending; Medicaid spending; Long-term

care insurance; Biomarker; Cerebrospinal fluid; Brain imaging

1. About this report

2017 Alzheimer’s Disease Facts and Figures is a statistical resource for U.S. data related to Alzheimer’s disease, the most common cause of dementia. Background

[email protected]. Tel.: 11-312-335-5893; Fax: 11-866-

16/j.jalz.2017.02.001

and context for interpretation of the data are contained in the overview. Additional sections address prevalence, mortality and morbidity, caregiving, and use and costs of health care, long-term care and hospice. The Special Report (doi: 10.1016/j.jalz.2017.02.006) examines what we have learned about the diagnosis of Alzheimer’s disease through research, and how we could identify and count the number of people with the disease in the future.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373326

1.1. Specific information in this year’s report

Specific information in this year’s Alzheimer’s Disease Facts and Figures includes: � Proposed guidelines for diagnosing Alzheimer’s disease

from the National Institute on Aging and the Alzheimer’s Association.

� How the diagnosis of Alzheimer’s disease has evolved from 1984 to today.

� Overall number of Americans with Alzheimer’s dementia nationally and for each state.

� Proportion of women and men with Alzheimer’s or other dementias.

� Lifetime risk for developing Alzheimer’s dementia. � Number of deaths due to Alzheimer’s disease nationally

and for each state, and death rates by age. � Number of family caregivers, hours of care provided,

economic value of unpaid care nationally and for each state, and the impact of caregiving on caregivers.

� Cost of care for individuals with Alzheimer’s or other dementias in the United States in 2017, including costs paidbyMedicare andMedicaidandcostspaid out ofpocket.

� Health care and long-term care payments for Medicare beneficiaries with Alzheimer’s or other dementias compared with beneficiaries without dementia.

� Medicaid costs for people with Alzheimer’s and other dementias, by state.

The Appendices detail sources and methods used to derive statistics in this report.

This report frequently cites statistics that apply to individuals with dementia regardless of the cause. When possible, specific information about Alzheimer’s dementia is provided; in other cases, the reference may be a more general one of “Alzheimer’s or other dementias.”

1.2. What is “Alzheimer’s Dementia”?

As discussed in the overview, under the 1984 diagnostic guidelines, an individual with Alzheimer’s disease must have symptoms of dementia. In contrast, under the proposed revised guidelines of 2011, Alzheimer’s disease encompasses an entire continuum from the initial pathologic changes in the brain before symptoms appear through the dementia caused by the accumulation of brain changes. This means that Alzheimer’s disease includes not only those with dementia due to the dis- ease, but also those with mild cognitive impairment due to Alzheimer’s and asymptomatic individuals who have verified biomarkers of Alzheimer’s. As a result, what was “Alzheimer’s disease” under the 1984 guidelines is now more accurately labeled, under the 2011 guidelines, as “dementia due to Alzheimer’s” or “Alzheimer’s dementia” — one stage in the continuum of the disease.

This year’s Alzheimer’s Disease Facts and Figures re- flects this change in understanding and terminology. That is, the term “Alzheimer’s disease” is now used only in those

instances that refer to the underlying disease and/or the entire continuum of the disease. The term “Alzheimer’s de- mentia” is used to describe those in the dementia stage of the continuum. Thus, in most instances where past reports used “Alzheimer’s disease,” this year’s report now uses “Alz- heimer’s dementia.” The data examined are the same and are comparable across years — only the way of describing the affected population has changed. For example, 2016 Alz- heimer’s Disease Facts and Figures (DOI: http://dx.doi.org/ 10.1016/j.jalz.2016.03.001) reported that 5.4 million indi- viduals in the United States had “Alzheimer’s disease.” The 2017 report states that 5.5 million individuals have “Alz- heimer’s dementia.” These prevalence estimates are compa- rable: they both identify the number of individuals who are in the dementia stage of Alzheimer’s disease. The only thing that has changed is the term used to describe their condition.

2. Overview of Alzheimer’s disease

Alzheimer’s disease is a degenerative brain disease and the most common cause of dementia [1,2]. Dementia is a syndrome—a group of symptoms—that has a number of causes. The characteristic symptoms of dementia are difficulties with memory, language, problem-solving and other cognitive skills that affect a person’s ability to perform everyday activities. These difficulties occur because nerve cells (neurons) in parts of the brain involved in cognitive function have been damaged or destroyed. In Alzheimer’s disease, neurons in other parts of the brain are eventually damaged or destroyed as well, including those that enable a person to carry out basic bodily functions such as walking and swallowing. People in the final stages of the disease are bed-bound and require around-the-clock care. Alzheimer’s disease is ultimately fatal.

2.1. Dementia

When an individual has symptoms of dementia, a physi- cian will conduct tests to identify the cause. Different causes of dementia are associated with distinct symptom patterns and brain abnormalities, as described in Table 1. Studies show that many people with dementia symptoms, especially those in the older age groups, have brain abnormalities associated with more than one cause of dementia [3–7].

In some cases, individuals with symptoms of dementia do not actually have dementia, but instead have a condition whose symptoms mimic those of dementia. Common causes of dementia-like symptoms are depression, delirium, side effects from medications, thyroid problems, certain vitamin deficiencies and excessive use of alcohol. Unlike dementia, these conditions often may be reversed with treatment. One meta-analysis, a method of analysis in which results of multiple studies are examined, reported that 9 percent of people with dementia-like symptoms did not in fact have dementia, but had other conditions that were potentially reversible [8].

Table 1

Causes of dementia and associated characteristics*

Cause Characteristics

Alzheimer’s disease Most common cause of dementia; accounts for an estimated 60 percent to 80 percent of cases. Autopsy studies show that about

half of these cases involve solely Alzheimer’s pathology; many of the remaining cases have evidence of additional pathologic

changes related to other dementias. This is called mixed pathology and if recognized during life is called mixed dementia.

Difficulty remembering recent conversations, names or events is often an early clinical symptom; apathy and depression are also

often early symptoms. Later symptoms include impaired communication, disorientation, confusion, poor judgment, behavior

changes and, ultimately, difficulty speaking, swallowing and walking.

Revised guidelines for diagnosing Alzheimer’s were proposed and published in 2011. They recommend that Alzheimer’s be

considered a slowly progressive brain disease that begins well before clinical symptoms emerge.

The hallmark pathologies of Alzheimer’s are the progressive accumulation of the protein fragment beta-amyloid (plaques)

outside neurons in the brain and twisted strands of the protein tau (tangles) inside neurons. These changes are eventually

accompanied by the damage and death of neurons.

Vascular dementia Previously known as multi-infarct or post-stroke dementia, vascular dementia is less common as a sole cause of dementia than

Alzheimer’s, accounting for about 10 percent of dementia cases. However, it is very common as a mixed pathology in older

individuals with Alzheimer’s dementia, about 50 percent of whom have pathologic evidence of infarcts (silent strokes) [10].

Impaired judgment or impaired ability to make decisions, plan or organize is more likely to be the initial symptom, as opposed to

the memory loss often associated with the initial symptoms of Alzheimer’s. In addition to changes in cognition, people with

vascular dementia can have difficulty with motor function, especially slow gait and poor balance.

Vascular dementia occurs most commonly from blood vessel blockage or damage leading to infarcts (strokes) or bleeding in the

brain. The location, number and size of the brain injuries determine whether dementia will result and how the individual’s

thinking and physical functioning will be affected.

In the past, evidence of vascular dementia was used to exclude a diagnosis of Alzheimer’s (and vice versa). That practice is no

longer considered consistent with the pathologic evidence, which shows that the brain changes of Alzheimer’s and vascular

dementia commonly coexist. When there is clinical evidence of two or more causes of dementia, the individual is considered

to have mixed dementia.

Dementia with Lewy

bodies (DLB)

People with DLB have some of the symptoms common in Alzheimer’s, but are more likely to have initial or early symptoms of

sleep disturbances, well-formed visual hallucinations, and slowness, gait imbalance or other parkinsonian movement features.

These features, as well as early visuospatial impairment, may occur in the absence of significant memory impairment.

Lewy bodies are abnormal aggregations (or clumps) of the protein alpha-synuclein in neurons. When they develop in a part of the

brain called the cortex, dementia can result. Alpha-synuclein also aggregates in the brains of people with Parkinson’s disease

(PD), in which it is accompanied by severe neuronal loss in a part of the brain called the substantia nigra. While people with

DLB and PD both have Lewy bodies, the onset of the disease is marked by motor impairment in PD and cognitive impairment

in DLB.

The brain changes of DLB alone can cause dementia, but very commonly people with DLB have coexisting Alzheimer’s

pathology. In people with both DLB and Alzheimer’s pathology, symptoms of both diseases may emerge and lead to some

confusion in diagnosis. Vascular dementia can also coexist and contribute to the dementia. When evidence of more than one

dementia is recognized during life, the individual is said to have mixed dementia.

Mixed dementia Characterized by the hallmark abnormalities of more than one cause of dementia — most commonly Alzheimer’s combined with

vascular dementia, followed by Alzheimer’s with DLB, and Alzheimer’s with vascular dementia and DLB. Vascular dementia

with DLB is much less common [4,5].

Recent studies suggest that mixed dementia is more common than previously recognized, with about half of older people with

dementia having pathologic evidence of more than one cause of dementia [4,5]. Recent studies also show that the likelihood of

having mixed dementia increases with age and is highest in the oldest-old (people age 85 or older).

Frontotemporal lobar

degeneration (FTLD)

Includes dementias such as behavioral-variant FTLD, primary progressive aphasia, Pick’s disease, corticobasal degeneration and

progressive supranuclear palsy.

Typical early symptoms include marked changes in personality and behavior and/or difficulty with producing or comprehending

language. Unlike Alzheimer’s, memory is typically spared in the early stages of disease.

Nerve cells in the front (frontal lobe) and side regions (temporal lobes) of the brain are especially affected, and these regions

become markedly atrophied (shrunken). In addition, the upper layers of the cortex typically become soft and spongy and have

abnormal protein inclusions (usually tau protein or the transactive response DNA-binding protein).

The symptoms of FTLD may occur in those age 65 years and older, similar to Alzheimer’s, but most people with FTLD develop

symptoms at a younger age. About 60 percent of people with FTLD are ages 45 to 60. FTLD accounts for about 10 percent of

dementia cases.

Parkinson’s disease (PD) Problems with movement (slowness, rigidity, tremor and changes in gait) are common symptoms of PD.

In PD, alpha-synuclein aggregates appear in an area deep in the brain called the substantia nigra. The aggregates are thought to

cause degeneration of the nerve cells that produce dopamine.

The incidence of PD is about one-tenth that of Alzheimer’s.

As PD progresses, it often results in dementia secondary to the accumulation of Lewy bodies in the cortex (similar to DLB) or the

accumulation of beta-amyloid clumps and tau tangles (similar to Alzheimer’s).

(Continued)

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 327

Table 1

Causes of dementia and associated characteristics* (Continued)

Cause Characteristics

Creutzfeldt-Jakob disease This very rare and rapidly fatal disorder impairs memory and coordination and causes behavior changes.

Results from a misfolded protein (prion) that causes other proteins throughout the brain to misfold and malfunction.

May be hereditary (caused by a gene that runs in one’s family), sporadic (unknown cause) or caused by a known prion infection.

A specific form called variant Creutzfeldt-Jakob disease is believed to be caused by consumption of products from cattle affected

by mad cow disease.

Normal pressure

hydrocephalus

Symptoms include difficulty walking, memory loss and inability to control urination.

Accounts for less than 5 percent of dementia cases [11].

Caused by impaired reabsorption of cerebrospinal fluid and the consequent buildup of fluid in the brain, increasing pressure in the

brain.

People with a history of brain hemorrhage (particularly subarachnoid hemorrhage) and meningitis are at increased risk.

Can sometimes be corrected with surgical installation of a shunt in the brain to drain excess fluid.

*For more information on these and other causes of dementia, visit alz.org/dementia.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373328

2.2. Alzheimer’s disease

Alzheimer’s disease was first described in 1906, but about 70 years passed before it was recognized as a common cause of dementia and a major cause of death [9]. Not until then did Alzheimer’s disease become a significant area of research. Although the research that followed has revealed a great deal about Alzheimer’s, much is yet to be discovered about the precise biological changes that cause the disease, why it progresses more quickly in some than in others, and how the disease can be prevented, slowed or stopped.

2.2.1. Symptoms The differences between typical age-related cognitive

changes and signs of Alzheimer’s can be subtle (Table 2). Just as individuals are different, so are the Alz- heimer’s symptoms they may experience. The most com- mon initial symptom is a gradually worsening ability to remember new information. This occurs because the first neurons to be damaged and destroyed are usually in brain regions involved in forming new memories. As neurons in other parts of the brain are damaged and destroyed, indi- viduals experience other difficulties, including neurobeha- vioral symptoms such as agitation, sleeplessness and delusions.

The pace at which symptoms advance from mild to moderate to severe varies from person to person. As the disease progresses, cognitive and functional abilities decline. In the more advanced stages, people need help with basic activities of daily living, such as bathing, dressing, eating and using the bathroom; lose their ability to communicate; and become bed-bound and reliant on around-the-clock care. When individuals have difficulty moving, they are more vulnerable to infections, including pneumonia (infection of the lungs). Alzheimer’s-related pneumonia often contributes to the death of people with Alzheimer’s disease. When Alzheimer’s destroys cells in the areas of the brain that control swallowing, an individual becomes vulnerable to death by Alzheimer’s- related malnutrition and dehydration.

2.2.2. Diagnosis There is no single test for Alzheimer’s. Instead,

physicians, often with the help of specialists such as neurologists and geriatricians, use a variety of approaches and tools to help make a diagnosis. They include the following:

� Obtaining a medical and family history from the individual, including psychiatric history and history of cognitive and behavioral changes.

� Asking a family member to provide input about changes in thinking skills and behavior.

� Conducting cognitive tests and physical and neurologic examinations.

� Having the individual undergo blood tests and brain im- agingtoruleoutotherpotentialcausesofdementiasymp- toms, such as a tumor or certain vitamin deficiencies.

Diagnosing Alzheimer’s requires a careful and compre- hensive medical evaluation. Although physicians can almost always determine if a person has dementia, it may be difficult to identify the exact cause. Several days or weeks may be needed for the individual to complete the required tests and examinations and for the physician to interpret the results and make a diagnosis.

2.2.3. Brain changes associated with Alzheimer’s disease A healthy adult brain has about 100 billion neurons, each

with long, branching extensions. These extensions enable individual neurons to form connections with other neurons. At such connections, called synapses, information flows in tiny bursts of chemicals that are released by one neuron and detected by a receiving neuron. The brain contains about 100 trillion synapses. They allow signals to travel rapidly through the brain’s neuronal circuits, creating the cellular basis of memories, thoughts, sensations, emotions, move- ments and skills.

The accumulation of the protein fragment beta-amyloid (called beta-amyloid plaques) outside neurons and the accumu- lationofanabnormal formof the proteintau(calledtautangles) inside neurons are two of several brain changes associated with

Table 2

Signs of Alzheimer’s or other dementias compared with typical age-related changes*

Signs of Alzheimer’s or other dementias Typical age-related changes

Memory loss that disrupts daily life: One of the most common signs of Alzheimer’s is memory loss,

especially forgetting recently learned information. Others include forgetting important dates or

events, asking for the same information over and over, and increasingly needing to rely on memory

aids (e.g., reminder notes or electronic devices) or family members for things that used to be handled

on one’s own.

Sometimes forgetting names or appointments,

but remembering them later.

Challenges in planning or solving problems: Some people experience changes in their ability to

develop and follow a plan or work with numbers. They may have trouble following a familiar recipe,

keeping track of monthly bills or counting change. They may have difficulty concentrating and take

much longer to do things than they did before.

Making occasional errors when balancing

a checkbook.

Difficulty completing familiar tasks at home, at work or at leisure: People with Alzheimer’s often

find it hard to complete daily tasks. Sometimes, people have trouble driving to a familiar location,

managing a budget at work or remembering the rules of a favorite game.

Occasionally needing help to use the settings on a

microwave or record a television show.

Confusion with time or place: People with Alzheimer’s can lose track of dates, seasons and the

passage of time. They may have trouble understanding something if it is not happening immediately.

Sometimes they forget where they are or how they got there.

Getting confused about the day of the week but

figuring it out later.

Trouble understanding visual images and spatial relationships: For some people, having vision

problems is a sign of Alzheimer’s. They may have difficulty reading, judging distance and

determining color or contrast, which may cause problems with driving.

Vision changes related to cataracts, glaucoma

or age-related macular degeneration.

New problems with words in speaking or writing: People with Alzheimer’s may have trouble

following or joining a conversation. They may stop in the middle of a conversation and have no idea

how to continue or they may repeat themselves. They may struggle with vocabulary, have problems

finding the right word or call things by the wrong name (e.g., calling a watch a “hand clock”).

Sometimes having trouble finding the right word.

Misplacing things and losing the ability to retrace steps: People with Alzheimer’s may put things in

unusual places, and lose things and be unable to go back over their steps to find them again.

Sometimes, they accuse others of stealing. This may occur more frequently over time.

Misplacing things from time to time and retracing

steps to find them.

Decreased or poor judgment: People with Alzheimer’s may experience changes in judgment or

decision-making. For example, they may use poor judgment when dealing with money, giving large

amounts to telemarketers. They may pay less attention to grooming or keeping themselves clean.

Making a bad decision once in a while.

Withdrawal from work or social activities: People with Alzheimer’s may start to remove themselves

from hobbies, social activities, work projects or sports. They may have trouble keeping up with a

favorite sports team or remembering how to complete a favorite hobby. They may also avoid being

social because of the changes they have experienced.

Sometimes feeling weary of work, family and

social obligations.

Changes in mood and personality: The mood and personalities of people with Alzheimer’s can

change. They can become confused, suspicious, depressed, fearful or anxious. They may be easily

upset at home, at work, with friends or in places where they are out of their comfort zones.

Developing very specific ways of doing things and

becoming irritable when a routine is disrupted.

*For more information about the symptoms of Alzheimer’s, visit alz.org/10signs.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 329

Alzheimer’s. Beta-amyloid plaques are believed to contribute to cell death by interfering with neuron-to-neuron communication at synapses, while tau tangles block the transport of nutrients and other essential molecules inside neurons. The brains of people with advanced Alzheimer’s disease show inflammation, dramatic shrinkage from cell loss, and widespread debris from dead and dying neurons.

Research suggests that the brain changes associated with Alzheimer’s may begin 20 or more years before symptoms appear [12–15]. When the initial changes occur, the brain compensates for them, enabling individuals to continue to function normally. As neuronal damage increases, the brain can no longer compensate for the changes and individuals show subtle cognitive decline. Later, neuronal damage is so significant that individuals show obvious cognitive decline, including symptoms such as memory loss or confusion as to time or place. Later still, basic bodily functions such as swallowing are impaired.

While research settings have the tools and expertise to identify some of the early brain changes of Alzheimer’s,

additional research is needed to fine-tune the tools’ accuracy before they become available for clinical use. In addition, treatments to prevent, slow or stop these changes are not yet available, althoughmanyare being tested in clinical trials.

2.2.4. Mild cognitive impairment (MCI): A potential precursor to Alzheimer’s and other dementias

MCI is a condition in which an individual has mild but measurable changes in thinking abilities that are noticeable to the person affected and to family members and friends, but do not affect the individual’s ability to carry out everyday activities. Approximately 15 percent to 20 percent of people age 65 or older have MCI [16]. People with MCI, especially MCI involving memory problems, are more likely to develop Alzheimer’s or other dementias than people without MCI [17,18]. A systematic review of 32 studies found that an average of 32 percent of individuals with MCI developed Alzheimer’s dementia in 5 years [19]. This is similar to a meta-analysis of 41 studies that found that among individuals with MCI who were tracked for 5 years or longer,

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373330

an average of 38 percent developed dementia [18]. Identifying which individuals with MCI are more likely to develop Alzheimer’s or other dementias is a major goal of current research.

Revised guidelines for diagnosing Alzheimer’s disease that were published in 2011 [20–23] suggest that in some cases MCI is actually an early stage of Alzheimer’s (called MCI due to Alzheimer’s disease) or another form of dementia. However, MCI can develop for reasons other than Alzheimer’s, and MCI does not always lead to dementia. In some individuals, MCI reverts to normal cognition or remains stable. In other cases, such as when a medication causes cognitive impairment, MCI is mistakenly diagnosed. Therefore, it’s important that people experiencing cognitive impairment seek help as soon as possible for diagnosis and possible treatment.

2.2.5. Genetic abnormalities associated with Alzheimer’s Certain genetic mutations and the extra copy of chromo-

some 21 that characterizes Down syndrome are uncommon genetic changes that affect the risk of Alzheimer’s. There are alsocommonvariationsingenesthataffectriskofAlzheimer’s.

2.2.5.1. Genetic mutations A small percentage of Alzheimer’s cases (an estimated 1

percent or less) [24] develop as a result of mutations to any of three specific genes. A genetic mutation is an abnormal change in the sequence of chemical pairs that make up genes. These mutations involve the gene for the amyloid precursor protein (APP) and the genes for the presenilin 1 and presenilin 2 proteins. Those inheriting a mutation to the APP or presenilin 1 genes are guaranteed to develop Alzheimer’s. Those inheriting a mutation to the presenilin 2 gene have a 95 percent chance of developing the disease [25]. Individuals with mutations in any of these three genes tend to develop Alzheimer’s symptoms before age 65, some- times as early as age 30, while the vast majority of individuals with Alzheimer’s have late-onset disease, in which symptoms become apparent at age 65 or later.

2.2.5.2. Down syndrome About 400,000 Americans have Down syndrome [26]. In

Down syndrome, an individual is born with an additional copy of chromosome 21, one of the 23 human chromosomes. Scientists are not certain why people with Down syndrome are at higher risk of developing Alzheimer’s, but it may be related to the additional copy of chromosome 21. This chro- mosome includes a gene that encodes for the production of APP, which in people with Alzheimer’s is cut into beta-amyloid fragments that accumulate into plaques. Having an extra copy of chromosome 21 may increase the amount of beta-amyloid fragments in the brain.

By age 40, most people with Down syndrome have signif- icant levels of beta-amyloid plaques and tau tangles in their brains [27]. As with all adults, advancing age increases the likelihood that a person with Down syndrome will exhibit

symptoms of Alzheimer’s. According to the National Down Syndrome Society, about 30 percent of people with Down syndrome who are in their 50s have Alzheimer’s dementia [28]. Fifty percent or more of people with Down syndrome will develop Alzheimer’s dementia as they age [29].

2.2.6. Risk factors for Alzheimer’s With the exception of cases of Alzheimer’s caused by

genetic abnormalities, experts believe that Alzheimer’s, like other common chronic diseases, develops as a result of multiple factors rather than a single cause.

2.2.6.1. Age, family history and the apolipoprotein E (APOE) e4 gene

The greatest risk factors for late-onset Alzheimer’s are older age [30,31], having a family history of Alzheimer’s [32–35] and carrying the APOE e4 gene [36,37].

2.2.6.1.1. Age Age is the greatest of these three risk factors, with the vast

majority of people with Alzheimer’s dementia being age 65 or older. As noted in the Prevalence section, the percent- age of people with Alzheimer’s dementia increases dramat- ically with age: 3 percent of people age 65-74, 17 percent of people age 75-84, and 32 percent of people age 85 or older have Alzheimer’s dementia [31]. It is important to note that Alzheimer’s dementia is not a normal part of aging, and older age alone is not sufficient to cause Alz- heimer’s dementia.

2.2.6.1.2. Family history A family history of Alzheimer’s is not necessary for an

individual to develop the disease. However, individuals who have a parent, brother or sister with Alzheimer’s are more likely to develop the disease than those who do not have a first-degree relative with Alzheimer’s [32,38]. Those who have more than one first-degree relative with Alzheimer’s are at even higher risk [35]. When diseases run in families, heredity (genetics), shared environmental and lifestyle factors (for example, access to healthy foods and level of physical activity), or both, may play a role. The increased risk associated with having a family history of Alzheimer’s is not entirely explained by whether the individual has inherited the APOE e4 risk gene.

2.2.6.1.3. APOE e4 gene The APOE gene provides the blueprint for a protein that

transports cholesterol in the bloodstream. Everyone inherits one of three forms of the APOE gene—e2, e3 or e4 — from each parent. The e3 form is the most common, with 50 percent to 90 percent of individuals having one or two copies [39]. The e4 form is the next most common, with 5 percent to 35 percent having one or two copies, and the e2 form is the least common, with 1 percent to 5 percent having one or two copies [39]. The estimated distribution of the six possible e2, e3 and e4 pairs is shown in Table 3.

Table 3

Estimated percentages of the U.S. population with the six possible e2, e3

and e4 pairs of the apolipoprotein E (APOE) gene

APOE pair Percentage

e2/e2 0.5

e2/e3 11

e2/e4 2

e3/e3 61

e3/e4 23

e4/e4 2

NOTE. Created from data from Raber and colleagues [40].

Percentages do not total 100 due to rounding.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 331

Having the e4 form increases one’s risk of developing Alzheimer’s compared with having the e3 form, while having the e2 form may decrease one’s risk compared with having the e3 form. Those who inherit one copy of the e4 form have three times the risk of developing Alzheimer’s compared with those with the e3 form, while those who inherit two copies of the e4 form have an 8- to 12-fold risk [38,41,42]. In addition, those with the e4 form are more likely to develop Alzheimer’s at a younger age than those with the e2 or e3 forms of the APOE gene [43]. A meta-analysis including 20 published articles describing the frequency of the e4 form among people in the United States who had been diagnosed with Alzheimer’s found that 56 percent had one copy of the APOE e4 gene, and 11 percent had two copies of the APOE e4 gene [44]. Another study found that among 1770 diagnosed individuals from 26 Alzheimer’s disease centers, 65 percent had at least one copy of the APOE e4 gene [45].

Unlike inheriting a genetic mutation that causes Alzheimer’s, inheriting the APOE e4 gene does not guarantee that an individual will develop Alzheimer’s. This is also true for more than 20 recently identified genes that appear to affect the risk of Alzheimer’s. These genes are believed to have a limited effect on the overall prevalence of Alzheimer’s because they are rare or only slightly increase risk [46].

2.2.6.2. Modifiable risk factors Although risk factors such as age and family history

cannot be changed, other risk factors can be changed, or modified, to reduce risk of cognitive decline and dementia. A report [47] evaluating the state of the evidence on the effects of modifiable risk factors on cognitive decline and dementia concluded that there is sufficiently strong evidence, from a population-based perspective, that regular physical activity and management of cardiovascular risk factors (especially diabetes, obesity, smoking and hypertension) reduce the risk of cognitive decline and may reduce the risk of dementia. It also concluded that there is sufficiently strong evidence that a healthy diet and lifelong learning/cognitive training may reduce the risk of cognitive decline. A report from the Institute of Medicine examined the evidence regarding modifiable risk factors for cognitive decline and reached similar conclusions [48].

2.2.6.2.1. Cardiovascular disease risk factors Brain health is affected by the health of the heart and

blood vessels. Although it makes up just 2 percent of body weight, the brain consumes 20 percent of the body’s oxygen and energy supplies [49]. A healthy heart ensures that enough blood is pumped to the brain, while healthy blood vessels enable the oxygen- and nutrient-rich blood to reach the brain so it can function normally.

Many factors that increase the risk of cardiovascular dis- ease are also associated with a higher risk of dementia. These factors include smoking [50–52], obesity in midlife [53–55] and diabetes [56–59]. Some studies propose that impaired glucose processing (a precursor to diabetes) may also result in an increased risk for dementia [53,60,61]. Hypertension [53,62–64] and high cholesterol [65,66] in midlife are also implicated as risk factors for dementia.

Conversely, factors that protect the heart may also protect the brain and reduce the risk of developing Alzheimer’s or other dementias. Physical activity [59,67–70] appears to be one of these factors. In addition, emerging evidence suggests that consuming a diet that benefits the heart, such as one that is lower in saturated fats, may be associated with reduced Alzheimer’s and dementia risk [59,71–75].

Researchers have begun studying combinations of health factors and lifestyle behaviors (for example, blood pressure and physical activity) to learn whether combinations of risk factors better identify Alzheimer’s and dementia risk than individual risk factors, as well as whether intervening on multiple risk factors simultaneously has a greater chance of reducing risk than addressing a single risk factor [76].

2.2.6.2.2. Education People with more years of formal education are at lower

risk for Alzheimer’s and other dementias than those with fewer years of formal education [77–81]. Some researchers believe that having more years of education builds a “cognitive reserve” that enables individuals to better compensate for brain changes that could result in symptoms of Alzheimer’s or other dementias [80,82,83]. According to the cognitive reserve hypothesis, having more years of education increases the connections between neurons, enabling the brain to use alternate routes of neuron-to- neuron communication to complete cognitive tasks when the usual routes have neuronal gaps because of Alzheimer’s.

Some scientists believe other factors may contribute to or explain the increased risk of dementia among those with fewer years of formal education. These factors include an increased likelihood of having occupations that are less mentally stimulating [84–87]. In addition, having fewer years of formal education is associated with lower socioeconomic status [88], which in turn may increase one’s likelihood of experiencing poor nutrition and decrease one’s ability to afford health care or medical treatments, such as treatments for cardiovascular risk factors. Finally, in the United States, people with fewer years of education tend to have more cardiovascular risk factors for Alzheimer’s,

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373332

including being less physically active [89] and having a higher risk of diabetes [90–92] and cardiovascular disease [93].

2.2.6.2.3. Social and cognitive engagement Additional studies suggest that remaining socially and

mentally active throughout life may support brain health and possibly reduce the risk of Alzheimer’s and other de- mentias [94–104]. Remaining socially and mentally active may help build cognitive reserve, but the exact mechanism by which this may occur is unknown. More research is needed to better understand how social and cognitive engagement may affect biological processes to reduce risk.

2.2.6.2.4. Traumatic brain injury (TBI) TBI is the disruption of normal brain function caused by

a blow or jolt to the head or penetration of the skull by a foreign object. According to the Centers for Disease Con- trol and Prevention (CDC), an estimated 1.7 million Amer- icans will sustain a TBI in any given year [105]. Falls and motor vehicle accidents are the leading causes of TBI [105,106].

Twoways to classify the severity of TBI are by the duration of loss of consciousness or post-traumatic amnesia [107] and the individual’s initial score on the 15-point Glasgow Coma Scale [108]. Based on these classification approaches,

� Mild TBI (also known as a concussion) is characterized by loss of consciousness or post-traumatic amnesia lasting 30 minutes or less, or an initial Glasgow score of 13-15; about 75 percent of TBIs are mild [106].

� Moderate TBI is characterized by loss of consciousness or post-traumatic amnesia lasting more than 30 minutes butlessthan 24hours,oraninitial Glasgowscore of9-12.

� Severe TBI is characterized by loss of consciousness or post-traumatic amnesia lasting 24 hours or more, or an initial Glasgow score of 8 or less.

Solid evidence indicates that moderate and severe TBI in- crease the risk of developing certain forms of dementia [107,109–112]. Those who experience repeated head injuries (such as boxers, football players and combat veterans) may be at an even higher risk of dementia, cognitive impairment and neurodegenerative disease [113–122].

Chronic traumatic encephalopathy (CTE) is a neuropatho- logic diagnosis (meaning it is characterized by brain changes thatcan onlybe identified atautopsy) associated withrepeated blows to the head, such as those that may occur while playing contact sports.Itisalsoassociatedwiththe developmentofde- mentia. Currently, there is no test to determine if someone has CTE-related brain changes during life. Other than repeated brain trauma, such as TBI, the causes and risk factors for CTE remain unknown. Like Alzheimer’s dementia, at au- topsy, CTE is characterized by tangles of an abnormal form of the protein tau in the brain. Unlike Alzheimer’s, these tan- gles typically appear around small blood vessels, and beta- amyloid plaques are only present in certain circumstances [123]. How the brain changes associated with CTE are linked

to cognitive or behavioral dysfunction is unclear. It is thought to be caused by repetitive TBI.

Individuals can decrease their risk of TBI by ensuring their living environments are well lit and free of tripping hazards, wearing seatbelts while traveling, and wearing helmets when on a bicycle, snowmobile or other open, unrestrained vehicle. Athletes and members of the military who have experienced repeated concussions may be able to prevent injury before recovery by following clinical guidelines for return to play or military duty.

2.2.7. Treatment of Alzheimer’s dementia

2.2.7.1. Pharmacologic treatment None of the pharmacologic treatments (medications)

available today for Alzheimer’s dementia slows or stops the damage and destruction of neurons that cause Alzheimer’s symptoms and make the disease fatal. The six drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s temporarily improve symptoms by increasing the amount of chemicals called neurotransmitters in the brain.A1 The effectiveness of these drugs varies from person to person and is limited in duration.

In the decade of 2002-2012, 244 drugs for Alzheimer’s were tested in clinical trials registered with clinicaltrials. gov, a National Institutes of Health registry of publicly and privately funded clinical studies [124]. Only one of the 244 drugs successfully completed clinical trials and went on to receive approval from the FDA. Many factors contribute to the difficulty of developing effective treatments for Alzheimer’s. These factors include the high cost of drug development, the relatively long time needed to observe whether an investigational treatment affects disease progression, and the structure of the brain, which is protected by the blood-brain barrier, through which only very specialized small-molecule drugs can cross.

2.2.7.2. Non-pharmacologic therapy Non-pharmacologic therapies are those that do not involve

medication. Non-pharmacologic therapies are often used with the goal of maintaining or improving cognitive function, the ability to perform activities of daily living or overall quality of life. They also may be used with the goal of reducing behavioral symptoms such as depression, apathy, wandering, sleep disturbances, agitation and aggression. Examples include computerized memory training, listening to favorite music as a way to stir recall, and incorporating special lighting to lessen sleep disorders. As with current pharmacologic therapies, non-pharmacologic therapies have not been shown to alter the course of Alzheimer’s disease.

Reviews and meta-analyses of non-pharmacologic therapies tested in randomized controlled trials (in which participants are randomly assigned to either receive or not receive a therapy, and the results of the two groups are compared) have found that some are beneficial to people with Alzheimer’s dementia. Among these are exercise [125,126] and cognitive stimulation [127]. Specifically, a

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 333

meta-analysis [125] found that aerobic exercise and a combination of aerobic and non-aerobic exercise can improve cognitive function, while a systematic review [126] found that exercise has a positive effect on overall cognitive function and is associated with a slower rate of cognitive decline in people with Alzheimer’s dementia. However, researchers caution that additional randomized controlled trials involving larger numbers of participants are needed to understand to what extent exercise may slow cognitive decline. A second systematic review [127] found that cognitive stimulation had beneficial effects on cognitive function and some aspects of well-being.

2.2.8. Living with Alzheimer’s Despite the lack of therapies that slow or stop

Alzheimer’s, studies have consistently shown that active management of Alzheimer’s and other dementias can improve quality of life for affected individuals and their caregivers [128–130]. Active management includes:

� Appropriate use of available treatment options. � Effective management of coexisting conditions. � Coordination of care among physicians, other health

care professionals and lay caregivers. � Participation in activities that are meaningful and bring

purpose to one’s life. � Having opportunities to connect with others living with

dementia; support groups and supportive services are examples of such opportunities.

To learn more about managing Alzheimer’s dementia, as well as practical information for living with dementia and being a caregiver, visit alz.org.

2.3. A modern diagnosis of Alzheimer’s disease: Revised guidelines

In 2011, the National Institute on Aging (NIA) and the Alzheimer’s Association proposed revised guidelines for diagnosing Alzheimer’s disease [20–23]. These guidelines updated diagnostic criteria and guidelines published in 1984 by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Association, then known as the Alzheimer’s Disease and Related Disorders Association (ADRDA) [131]. In 2012, the NIA and the Alzheimer’s Association also developed new guidelines to help pathologists describe and categorize the brain changes associated with Alzheimer’s and other dementias on autopsy [132].

2.3.1. Differences between the original and revised guidelines

The 1984 diagnostic criteria and guidelines were based chiefly on a doctor’s clinical judgment about the cause of an individual’s symptoms, taking into account reports from the individual, family members and friends; results of cognitive tests; and general neurological assessment. The

revised guidelines incorporate the same steps for diagnosis, but also incorporate biomarker tests.

A biomarker is a biological factor that can be measured to indicate the presence or absence of disease, or the risk of developing a disease. For example, blood glucose level is a biomarker of diabetes, and cholesterol level is a biomarker of heart disease risk. Among several factors being studied as possible biomarkers for Alzheimer’s are the amount of beta-amyloid in the brain as shown on positron emission tomography (PET) imaging and levels of certain proteins in fluid (for example, levels of beta-amyloid and tau in the cerebrospinal fluid and levels of particular groups of proteins in blood). Finding a simple and inexpensive test, such as a blood test, to diagnose Alzheimer’s would be ideal for patients, physicians and scientists. Research is underway to develop such a test, but to date, no test has shown the accuracy and reliability needed to diagnose Alzheimer’s.

Another difference is that the revised guidelines identify two stages of Alzheimer’s disease: mild cognitive impairment (MCI) due to Alzheimer’s disease and dementia due to Alzheimer’s disease. In addition, the revised guidelines propose—for research purposes—a preclinical phase of Alzheimer’s that occurs before symptoms such as memory loss develop.

Dementia due to Alzheimer’s disease: This stage is characterized by noticeable memory, thinking and behavioral symptoms that impair a person’s ability to function in daily life.

MCI due to Alzheimer’s disease: People with MCI show cognitive decline greater than expected for their age and education level, but this decline does not significantly interfere with everyday activities. Approximately 15 percent to 20 percent of people age 65 or older have MCI [16].

Proposed for research—preclinical Alzheimer’s dis- ease: In this proposed stage, individuals may have measur- able changes in the brain, cerebrospinal fluid and/or blood (biomarkers) that indicate the earliest signs of disease, but they may have not yet developed noticeable symptoms such as memory loss. This proposed preclinical or presymptomatic stage reflects current thinking that Alzheimer’s-related brain changes may begin 20 years or more before symptoms occur [12–14]. Ongoing research continues to explore this possible stage of the disease.

In contrast, the 1984 criteria identify Alzheimer’s as a disease that begins when symptoms of dementia such as memory loss are already present and have impaired an individual’s ability to carry out daily tasks.

2.3.2. Looking to the future Many researchers believe that future treatments to slow or

stop the progression of Alzheimer’s disease and preserve brain function will be most effective when administered early in the disease, either at the MCI stage or during the proposed preclinical stage.

Fig. 1. Ages of people with Alzheimer’s disease in the United States, 2017.

Percentages do not total 100 because of rounding. Created from data from

Hebert and colleagues [31].A4

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373334

Biomarker tests will be essential to identify which individuals are in these early stages and should receive treatments that slow or stop the disease when such treatments are available. They also will be critical for moni- toring the effects of treatment. Furthermore, biomarkers play an important role in developing treatments because they enable researchers to identify which individuals to enroll in clinical trials of potential new therapies. By using biomarkers, researchers can enroll only those individuals with the brain changes that treatments target [133].

It’s important to note that the most effective biomarker test or combination of tests may differ depending on the stage of the disease and other factors [134].

For more information on the revised guidelines and their potential impact, see the Special Report.

3. Prevalence

Millions of Americans have Alzheimer’s or other demen- tias. As the size and proportion of the U.S. population age 65 and older continue to increase, the number of Americans with Alzheimer’s or other dementias will grow. This number will escalate rapidly in coming years, as the population of Americans age 65 and older is projected to nearly double from 48 million to 88 million by 2050 [135]. The baby boom generation has already begun to reach age 65 and beyond [136], the age range of greatest risk of Alzheimer’s; in fact, the first members of the baby boom generation turned 70 in 2016.

Thissectionreportsonthenumberandproportionofpeople with Alzheimer’s dementia to describe the magnitude of the burden of Alzheimer’s on the community and health care system. The prevalence of Alzheimer’s dementia refers to the proportion of people in a population who have Alzheimer’s dementia at a given point in time. Incidence, the number of new cases per year, is also provided as an estimateofthe risk ofdeveloping Alzheimer’s orother demen- tias for different age groups. Estimates from selected studies on the number and proportion of people with Alzheimer’s or other dementias vary depending on how each study was conducted. Data from several studies are used in this section.

3.1. Prevalence of Alzheimer’s and other dementias in the United States

An estimated 5.5 million Americans of all ages are living with Alzheimer’s dementia in 2017. This number includes an estimated 5.3 million people age 65 and olderA2 [31] and approximately 200,000 individuals under age 65 who have younger-onset Alzheimer’s, though there is greater uncertainty about the younger-onset estimate [137].

� One in 10 people age 65 and older (10 percent) has Alzheimer’s dementia [31].A3

� The percentage of people with Alzheimer’s dementia increases with age: 3 percent of people age 65-74, 17 percent of people age 75-84, and 32 percent

of people age 85 and older have Alzheimer’s dementia [31].

� Of people who have Alzheimer’s dementia, 82 percent are age 75 or older (Figure 1) [31].A4

The estimated number of people age 65 and older with Alzheimer’s dementia comes from a study using the latest data from the 2010 U.S. Census and the Chicago Health and Aging Project (CHAP), a population-based study of chronic health conditions of older people [31].

National estimates of the prevalence of all dementias are not available from CHAP, but they are available from other population-based studies including the Aging, Demographics, and Memory Study (ADAMS), a nationally representative sample of older adults [138,139].A5 Based on estimates from ADAMS, 14 percent of people age 71 and older in the United States have dementia [138].

Prevalence studies such as CHAP and ADAMS are de- signed so that everyone in the study is tested for dementia. But outside of research settings, only about half of those who would meet the diagnostic criteria for Alzheimer’s and other dementias are diagnosed with dementia by a physician [140–142]. Furthermore, as discussed in 2015 Alzheimer’s Disease Facts and Figures, fewer than half of those who have a diagnosis of Alzheimer’s or another dementia in their Medicare records (or their caregiver, if the person was too impaired to respond to the survey) report being told of the diagnosis [143–146]. Because Alzheimer’s dementia is underdiagnosed and underreported, a large portion of Americans with Alzheimer’s may not know they have it.

The estimates of the number and proportion of people who have Alzheimer’s in this section refer to people who have Alzheimer’s dementia. But as described in the Overview section and Special Report, revised diagnostic guidelines [20–23] propose that Alzheimer’s disease begins many years before the onset of dementia. More research is needed to estimate how many people may have MCI due to Alzheimer’s disease and how many people may be in the preclinical stage of Alzheimer’s disease. However, if Alzheimer’s disease could be accurately detected before dementia develops, the number of people

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 335

reported to have Alzheimer’s disease would change to include more than just people who have been diagnosed with Alzheimer’s dementia.

3.1.1. Subjective cognitive decline The experience of worsening or more frequent confusion

or memory loss (often referred to as subjective cognitive decline) is one of the earliest warning signs of Alzheimer’s disease and may be a way to identify people who are at high risk of developing Alzheimer’s or other dementias as well as MCI [147–151]. Subjective cognitive decline does not refer to someone occasionally forgetting their keys or the name of someone they recently met; it refers to more serious issues such as having trouble remembering how to do things one has always done or forgetting things that one would normally know. Not all of those who experience subjective cognitive decline go on to develop MCI or dementia, but many do [152–154]. According to a recent study, only those who over time consistently reported subjective cognitive decline that they found worrisome were at higher risk for developing Alzheimer’s dementia [155]. Data from the 2015 Behavioral Risk Factor Surveil- lance System (BRFSS) survey, which included questions on self-perceived confusion and memory loss for people in 33 U.S. states and the District of Columbia, showed that 12 percent of Americans age 45 and older reported subjec- tive cognitive decline, but 56 percent of those who reported it had not consulted a health care professional about it [156]. Individuals concerned about declines in memory and other cognitive abilities should consult a health care professional.

3.1.2. Differences between women and men in the prevalence of Alzheimer’s and other dementias

More women than men have Alzheimer’s or other demen- tias. Almost two-thirds of Americans with Alzheimer’s are women [31].A6 Of the 5.3 million people age 65 and older with Alzheimer’s in the United States, 3.3 million are women and 2.0 million are men [31].A6 Based on estimates from ADAMS, among people age 71 and older, 16 percent of women have Alzheimer’s or other dementias compared with 11 percent of men [138,157].

There are a number of potential biological and social reasons why more women than men have Alzheimer’s or other dementias [158]. The prevailing view has been that this discrepancy is due to the fact that women live longer than men on average, and older age is the greatest risk factor for Alzheimer’s [157,159,160]. Many studies of incidence (which indicates risk of developing disease) of Alzheimer’s or any dementia [161] have found no significant difference between men and women in the proportion who develop Alzheimer’s or other dementias at any given age. A recent study using data from the Framingham Heart Study suggests that because men in middle age have a higher rate of death from cardiovascular disease than women in middle age, men who survive beyond age 65 may have a healthier

cardiovascular risk profile and thus an apparent lower risk for dementia than women of the same age [160]. Epidemiol- ogists call this “survival bias” because the men who survive to older ages and are included in studies tend to be the healthiest men; as a result, they may have a lower risk of developing Alzheimer’s and other dementias than the men who died at an earlier age from cardiovascular disease. More research is needed to support this finding.

However, researchers have recently begun to revisit the question of whether the risk of Alzheimer’s could actually be higher for women at any given age due to biological or genetic variations or differences in life experiences [162]. A large study showed that the APOE e4 genotype, the best known genetic risk factor for Alzheimer’s dementia, may have a stronger association with Alzheimer’s dementia in women than in men [163,164]. It is unknown why this may be the case, but some evidence suggests that it may be due to an interaction between the APOE e4 genotype and the sex hormone estrogen [165,166]. Finally, because low education is a risk factor for dementia [80–83,88,161], it is possible that lower educational attainment in women than in men born in the first half of the 20th century could account for a higher risk of Alzheimer’s and other dementias in women [167].

3.1.3. Racial and ethnic differences in the prevalence of Alzheimer’s and other dementias

Although there are more non-Hispanic whites living with Alzheimer’s and other dementias than any other racial or ethnic group in the United States, older African- Americans and Hispanics are more likely, on a per-capita basis, than older whites to have Alzheimer’s or other de- mentias [168–173]. A review of many studies by an expert panel concluded that older African-Americans are about twice as likely to have Alzheimer’s or other demen- tias as older whites [174,175], and Hispanics are about one and one-half times as likely to have Alzheimer’s or other dementias as older whites [175–177].A7 Currently, there is not enough evidence from population-based cohort studies in which everyone is tested for dementia to estimate the national prevalence of Alzheimer’s and other dementias in other racial and ethnic groups. However, a study exam- ining electronic medical records for members of a large health plan in California indicated that dementia inci- dence—determined by the presence of a dementia diagnosis in one’s medical record—was highest in African-Americans, intermediate for Latinos (the term used in the study for those who self-reported as Latino or Hispanic) and whites, and lowest for Asian-Americans [178].

Variations in health, lifestyle and socioeconomic risk factors across racial groups likely account for most of the differences in risk of Alzheimer’s and other dementias by race [179]. Despite some evidence that the influence of genetic risk factors on Alzheimer’s and other dementias may differ by race [180,181], genetic factors do not appear to account for the large prevalence differences among

Table 4

Projections of total numbers of Americans age 65 and older with

Alzheimer’s dementia by state

State

Projected number

with Alzheimer’s

(in thousands)

Percentage

change

2017 2025 2017-2025

Alabama 90 110 22.2

Alaska 7.1 11 54.9

Arizona 130 200 53.8

Arkansas 55 67 21.8

California 630 840 33.3

Colorado 69 92 33.3

Connecticut 75 91 21.3

Delaware 18 23 27.8

District of Columbia 9 9 0.0

Florida 520 720 38.5

Georgia 140 190 35.7

Hawaii 27 35 29.6

Idaho 24 33 37.5

Illinois 220 260 18.2

Indiana 110 130 18.2

Iowa 64 73 14.1

Kansas 52 62 19.2

Kentucky 70 86 22.9

Louisiana 85 110 29.4

Maine 27 35 29.6

Maryland 100 130 30.0

Massachusetts 120 150 25.0

Michigan 180 220 22.2

Minnesota 92 120 30.4

Mississippi 53 65 22.6

Missouri 110 130 18.2

Montana 20 27 35.0

Nebraska 33 40 21.2

Nevada 43 64 48.8

New Hampshire 24 32 33.3

New Jersey 170 210 23.5

New Mexico 38 53 39.5

New York 390 460 17.9

North Carolina 160 210 31.3

North Dakota 14 16 14.3

Ohio 210 250 19.0

Oklahoma 63 76 20.6

Oregon 63 84 33.3

Pennsylvania 270 320 18.5

Rhode Island 23 27 17.4

South Carolina 86 120 39.5

South Dakota 17 20 17.6

Tennessee 110 140 27.3

Texas 360 490 36.1

Utah 30 42 40.0

Vermont 12 17 41.7

Virginia 140 190 35.7

Washington 110 140 27.3

West Virginia 37 44 18.9

Wisconsin 110 130 18.2

Wyoming 9.4 13 38.3

NOTE. Created from data provided to the Alzheimer’s Association by

Weuve and colleagues [189]. A8

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373336

racial groups [179,182]. Instead, health conditions such as cardiovascular disease and diabetes, which are associated with an increased risk for Alzheimer’s and other dementias, are believed to account for these differences as they are more prevalent in African-American and Hispanic people [183,184]. Indeed, vascular dementia accounts for a larger proportion of dementia in African-Americans than in whites [181]. Socioeconomic characteristics, including lower levels of education, higher rates of poverty, and greater exposure to early life adversity and discrimination, may also increase risk in African-American and Hispanic commu- nities [183–185]. Some studies suggest that differences based on race and ethnicity do not persist in rigorous analyses that account for such factors [78,138,179].

There is evidence that missed diagnoses of Alzheimer’s and other dementias are more common among older African-Americans and Hispanics than among older whites [186,187]. Based on data for Medicare beneficiaries age 65 and older, Alzheimer’s or another dementia had been diagnosed in 6.9 percent of whites, 9.4 percent of African- Americans and 11.5 percent of Hispanics [188]. Although rates of diagnosis were higher among African-Americans than among whites, according to prevalence studies that detect all people who have dementia irrespective of their use of the health care system, the rates should be higher (i.e., twice as high as 6.9 percent, which is approximately 13.8 percent).

3.2. Estimates of the number of people with Alzheimer’s dementia by state

Table 4 lists the estimated number of people age 65 and older with Alzheimer’s dementia by state for 2017, the projected number for 2025, and the projected percentage change in the number of people with Alzheimer’s between 2017 and 2025 [189].A8 Comparable estimates and projections for other types of dementia are not available.

As shown in Figure 2, between 2017 and 2025 every state across the country is expected to experience an increase of at least 14 percent in the number of people with Alzheimer’s due to increases in the population age 65 and older. The West and Southeast are expected to experience the largest percentage increases in people with Alzheimer’s between 2017 and 2025. These increases will have a marked impact on states’ health care systems, as well as the Medicaid program, which covers the costs of long-term care and support for some older residents with dementia.

3.3. Incidence of Alzheimer’s dementia

While prevalence refers to existing cases of a disease in a population at a given time, incidence refers to new cases of a disease that develop in a given period of time in a defined population—in this case, the U.S. population age 65 or older. Incidence provides a measure of risk for developing a dis- ease. According to one study using data from the Established Populations for Epidemiologic Study of the Elderly

(EPESE), approximately 480,000 people age 65 or older will develop Alzheimer’s dementia in the United States in 2017.A9 The number of new cases of Alzheimer’s increases

Fig. 2. Projected increases between 2017 and 2025 in Alzheimer’s dementia prevalence by state. Change from 2017 to 2025 for Washington, D.C.: 0.0%.

Created from data provided to the Alzheimer’s Association by Weuve and colleagues [189].A8

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 337

dramatically with age: in 2017, there will be approximately 64,000 new cases among people age 65 to 74,173,000 new cases among people age 75 to 84, and 243,000 new cases among people age 85 and older (the “oldest-old”) [190].A9

This translates to approximately two new cases per 1000 people age 65 to 74, 12 new cases per 1000 people age 75 to 84, and 37 new cases per 1000 people age 85 and older.A9

A more recent study using data from the Adult Changes in Thought (ACT) study, a cohort of members of the Group Health health care delivery system in the Northwest United States, reported even higher incidence rates for Alzheimer’s dementia [161]. Because of the increasing number of people age 65 and older in the United States, particularly the oldest- old, the annual number of new cases of Alzheimer’s and other dementias is projected to double by 2050 [190].

� Every 66 seconds, someone in the United States develops Alzheimer’s dementia.A10

� By 2050, someone in the United States will develop Alzheimer’s dementia every 33 seconds.

A10

3.4. Lifetime risk of Alzheimer’s dementia

Lifetime risk is the probability that someone of a given age will develop a condition during his or her remaining life span. Data from the Framingham Heart Study were used to estimate lifetime risks of Alzheimer’s dementia by age and sex [160].A11 As shown in Figure 3, the study found that the estimated lifetime risk for Alzheimer’s dementia at age 45 was approximately one in five (20 percent) for women and one in 10 (10 percent) for men. The risks for both sexes were slightly higher at age 65 [160].

3.5. Trends in the prevalence and incidence of Alzheimer’s dementia

A growing number of studies indicate that the age-specific risk of Alzheimer’s and other dementias in the United States and other higher-income Western countries may have declined in the past 25 years [191–202], though results are mixed [30]. These declines have been attributed to increasing levels of

Fig. 3. Estimated lifetime risk for Alzheimer’s dementia, by sex, at age 45

and age 65. Created from data from Chene and colleagues [160].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373338

education and improved control of cardiovascular risk factors [193,199,202]. Such findings are promising and suggest that identifying and reducing risk factors for Alzheimer’s and other dementias may be effective. Although these findings indicate that a person’s risk of dementia at any given age may be decreasing slightly, it should be noted that the total number of Americans with Alzheimer’s or other dementias is expected to continue to increase dramatically because of the population’s shift to older ages. Furthermore, it is unclear whether these positive trends will continue into the future given worldwide trends showing increasing mid-life diabetes and obesity—potential risk factors for Alzheimer’s dementia—which may lead to a rebound in dementia risk in coming years [200,203,204]. Thus, while recent findings are promising, the social and economic burden of Alzheimer’s and other dementias will continue to grow. Moreover, 68 percent of the projected increase in the global prevalence and burden of dementia by 2050 will take place in low- and

Fig. 4. Projected number of people age 65 and older (total and by age group) in the

from Hebert and colleagues [31].A12

middle-income countries, where there is no evidence for a decline in the risk of Alzheimer’s and other dementias [205].

3.6. Looking to the future

The number of Americans surviving into their 80s, 90s and beyond is expected to grow dramatically due to medical advances, as well as social and environmental conditions [206]. Additionally, a large segment of the American popu- lation—the baby boom generation—has begun to reach age 65 and older, ages when the risk for Alzheimer’s and other dementias is elevated. By 2030, the segment of the U.S. pop- ulation age 65 and older will increase substantially, and the projected 74 million older Americans will make up over 20 percent of the total population (up from 14 percent in 2012) [206]. As the number of older Americans grows rapidly, so too will the numbers of new and existing cases of Alzheimer’s dementia, as shown in Figure 4 [31].A12

� In 2010, there were an estimated 454,000 new cases of Alzheimer’sdementia.By2030,thatnumberisprojected to be 615,000 (a 35 percent increase), and by 2050, 959,000 (a 110 percent increase from 2010) [190].

� By 2025, the number of people age 65 and older with Alzheimer’s dementia is estimated to reach 7.1 million—almost a 35 percent increase from the 5.3 million age 65 and older affected in 2017 [31].A13

� By 2050, the number of people age 65 and older with Alzheimer’s dementia may nearly triple, from 5.3 million to a projected 13.8 million, barring the development of medical breakthroughs to prevent or cure Alzheimer’s disease [31].A12 Previous estimates based on high-range projections of population growth provided by the U.S. Census suggest that this number may be as high as 16 million [207].A14

3.6.1. Growth of the oldest-old population Longer life expectancies and aging baby boomers will

also increase the number and percentage of Americans

U.S. population with Alzheimer’s dementia, 2010 to 2050. Created from data

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 339

who will be 85 and older. Between 2012 and 2050, the oldest-old are expected to increase from 14 percent of all people age 65 and older in the United States to 22 percent of all people age 65 and older [206]. This will result in an additional 12 million oldest-old people—individuals at the highest risk for developing Alzheimer’s demen- tia [206].

� In 2017, about 2.1 million people who have Alzheimer’s dementia are age 85 or older, accounting for 38 percent of all people with Alzheimer’s dementia [31].

� When the first wave of baby boomers reaches age 85 (in 2031), it is projected that more than 3 million people age 85 and older will have Alzheimer’s dementia [31].

� By 2050, as many as 7 million people age 85 and older may have Alzheimer’s dementia, accounting for half (51 percent) of all people 65 and older with Alzheimer’s dementia [31].

4. Mortality and morbidity

Alzheimer’s disease is officially listed as the sixth- leading cause of death in the United States [208]. It is the fifth-leading cause of death for those age 65 and older [198]. However, it may cause even more deaths than official sources recognize. Alzheimer’s is also a leading cause of disability and poor health (morbidity). Before a person with Alzheimer’s dies, he or she lives through years of morbidity as the disease progresses.

4.1. Deaths from Alzheimer’s disease

It is difficult to determine how many deaths are caused by Alzheimer’s disease each year because of the way

Fig. 5. Percentage changes in selected causes of death (all ages) between 2000 a

[208,219].

causes of death are recorded. According to data from the National Center for Health Statistics of the Centers for Disease Control and Prevention (CDC), 93,541 people died from Alzheimer’s disease in 2014 [208]. The CDC considers a person to have died from Alzheimer’s if the death certificate lists Alzheimer’s as the underlying cause of death, defined by the World Health Organization as “the disease or injury which initiated the train of events leading directly to death.” [209].

Severe dementia frequently causes complications such as immobility, swallowing disorders and malnutrition that significantly increase the risk of serious acute conditions that can cause death. One such condition is pneumonia, which is the most commonly identified cause of death among elderly people with Alzheimer’s or other dementias [210,211]. Death certificates for individuals with Alzheimer’s often list acute conditions such as pneumonia as the primary cause of death rather than Alzheimer’s [212–214]. As a result, people with Alzheimer’s disease who die due to these acute conditions may not be counted among the number of people who died from Alzheimer’s disease according to the World Health Organization definition, even though Alzheimer’s disease may well have caused the acute condition listed on the death certificate. This difficulty in using death certificates to accurately determine the number of deaths from Alzheimer’s has been referred to as a “blurred distinction between death with dementia and death from dementia.” [215].

Another way to determine the number of deaths from Alzheimer’s disease is through calculations that compare the estimated risk of death in those who have Alzheimer’s with the estimated risk of death in those who do not have Alzheimer’s. A study using data from the Rush Memory

nd 2014. Created from data from the National Center for Health Statistics

Table 5

Number of deaths and annual mortality rate (per 100,000 people) due to

Alzheimer’s disease, by state, 2014

State Number of deaths Mortality rate

Alabama 1885 38.9

Alaska 68 9.2

Arizona 2485 36.9

Arkansas 1193 40.2

California 12,644 32.6

Colorado 1364 25.5

Connecticut 923 25.7

Delaware 188 20.1

District of Columbia 119 18.1

Florida 5874 29.5

Georgia 2670 26.4

Hawaii 326 23.0

Idaho 376 23.0

Illinois 3266 25.4

Indiana 2204 33.4

Iowa 1313 42.3

Kansas 790 27.2

Kentucky 1523 34.5

Louisiana 1670 35.9

Maine 434 32.6

Maryland 934 15.6

Massachusetts 1688 25.0

Michigan 3349 33.8

Minnesota 1628 29.8

Mississippi 1098 36.7

Missouri 2053 33.9

Montana 253 24.7

Nebraska 515 27.4

Nevada 606 21.3

New Hampshire 396 29.8

New Jersey 1962 22.0

New Mexico 442 21.2

New York 2639 13.4

North Carolina 3246 32.6

North Dakota 364 49.2

Ohio 4083 35.2

Oklahoma 1227 31.6

Oregon 1411 35.5

Pennsylvania 3486 27.3

Rhode Island 403 38.2

South Carolina 1938 40.1

South Dakota 434 50.9

Tennessee 2672 40.8

Texas 6772 25.1

Utah 584 19.8

Vermont 266 42.5

Virginia 1775 21.3

Washington 3344 47.4

West Virginia 620 33.5

Wisconsin 1876 32.6

Wyoming 162 27.7

U.S. Total 93,541 29.3

NOTE. Created from data from the National Center for Health Statistics

[208]. A15

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373340

and Aging Project and the Religious Orders Study estimated that 500,000 deaths among people age 75 and older in the United States in 2010 could be attributed to Alzheimer’s (estimates for people age 65 to 74 were not available), meaning that those deaths would not be expected to occur in that year if those individuals did not have Alzheimer’s [216].

The true number of deaths caused by Alzheimer’s is somewhere between the number of deaths from Alzheimer’s recorded on death certificates and the number of people who have Alzheimer’s disease when they die. According to 2014 Medicare claims data, about one-third of all Medicare bene- ficiaries who die in a given year have been diagnosed with Alzheimer’s or another dementia [188]. Based on data from the Chicago Health and Aging Project (CHAP) study, in 2017 an estimated 700,000 people age 65 and older in the United States will have Alzheimer’s when they die. [217] Although some seniors who have Alzheimer’s disease at the time of death die from causes that are unrelated to Alzheimer’s, many of them die from Alzheimer’s disease itself or from conditions in which Alzheimer’s was a contributing cause, such as pneumonia.

Irrespective of the cause of death, among people age 70, 61 percent of those with Alzheimer’s are expected to die before age 80 compared with 30 percent of people without Alzheimer’s [218].

4.2. Public health impact of deaths from Alzheimer’s disease

As the population of the United States ages, Alzheimer’s is becoming a more common cause of death, and it is the only top 10 cause of death that cannot be prevented, cured or even slowed. Although deaths from other major causes have decreased significantly, official records indicate that deaths from Alzheimer’s disease have increased signifi- cantly. Between 2000 and 2014, deaths from Alzheimer’s disease as recorded on death certificates increased 89 percent, while deaths from the number one cause of death (heart disease) decreased 14 percent (Figure 5) [208]. The increase in the number of death certificates listing Alzheimer’s as the underlying cause of death reflects both changes in patterns of reporting deaths on death certificates over time as well as an increase in the actual number of deaths attributable to Alzheimer’s.

4.3. State-by-state deaths from Alzheimer’s disease

Table 5 provides information on the number of deaths due to Alzheimer’s by state in 2014, the most recent year for which state-by-state data are available. This information was obtained from death certificates and reflects the condi- tion identified by the physician as the underlying cause of death. The table also provides annual mortality rates by state to compare the risk of death due to Alzheimer’s disease across states with varying population sizes. For the United States as a whole, in 2014, the mortality rate for Alzheimer’s disease was 29 deaths per 100,000 people [208].A15

4.4. Alzheimer’s disease death rates

As shown in Figure 6, the rate of deaths attributed to Alz- heimer’s has risen substantially since 2000 [208]. Table 6

Fig. 6. U.S. annual Alzheimer’s death rate (per 100,000 people) by year. Created from data from the National Center for Health Statistics [208].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 341

showsthattherateofdeathfromAlzheimer’sincreasesdramat- ically with age, especially after age 65 [208]. The increase in the Alzheimer’s death rate over time has disproportionately affected the oldest-old [220]. Between 2000 and 2014, the death rate from Alzheimer’s increased only slightly for people age 65 to 74, but increased 33 percent for people age 75 to 84, and 51 percent for people age 85 and older.

4.5. Duration of illness from diagnosis to death

Studies indicate that people age 65 and older survive an average of 4 to 8 years after a diagnosis of Alzheimer’s de- mentia, yet some live as long as 20 years with Alzheimer’s [161,221–228]. This reflects the slow, insidious progression of Alzheimer’s. Of the total number of years that they live with Alzheimer’s dementia, individuals will spend an average of 40 percent of this time in dementia’s most severe stage [218]. Much of the time will be spent in a nursing home. At age 80, approximately 75 percent of peo- ple living with Alzheimer’s dementia are expected to be in a nursing home compared with only 4 percent of the general population at age 80 [218]. In all, an estimated two-thirds of those who die of dementia do so in nursing homes, compared with 20 percent of people with cancer and 28 percent of people dying from all other conditions [229].

4.6. Burden of Alzheimer’s disease

The long duration of illness before death contributes significantly to the public health impact of Alzheimer’s

Table 6

U.S. annual Alzheimer’s death rates (per 100,000 people) by age and year

Age 2000 2001 2002 2003 2004 2005 2006 20

45-54 0.2 0.2 0.1 0.2 0.2 0.2 0.2

55-64 2.0 2.1 1.9 2.0 1.8 2.1 2.1

65-74 18.7 18.6 19.6 20.7 19.5 20.2 19.9 2

75-84 139.6 147.2 157.7 164.1 168.5 177.0 175.0 17

851 667.7 725.4 790.9 846.8 875.3 935.5 923.4 92

NOTE. Created from data from the National Center for Health Statistics [208].

disease because much of that time is spent in a state of disability and dependence. Scientists have developed methods to measure and compare the burden of different diseases on a population in a way that takes into account not only the number of people with the condition, but also both the number of years of life lost due to that disease as well as the number of healthy years of life lost by virtue of being in a state of disability. These measures indicate that Alzheimer’s is a very burdensome disease and that the burden of Alzheimer’s has increased more dramati- cally in the United States than other diseases in recent years. The primary measure of disease burden is called disability-adjusted life years (DALYs), which is the sum of the number of years of life lost due to premature mor- tality and the number of years lived with disability, totaled across all those with the disease. Using this measure, Alz- heimer’s rose from the 25th most burdensome disease in the United States in 1990 to the 12th in 2010. No other disease or condition increased as much [230]. In terms of years of life lost, Alzheimer’s disease rose from 32nd to 9th, the largest increase for any disease. In terms of years lived with disability, Alzheimer’s disease went from ranking 17th to 12th; only kidney disease equaled Alzheimer’s in as high a jump in rank.

Taken together, these statistics indicate that not only is Alzheimer’s disease responsible for the deaths of more and more Americans, but also that the disease is contributing to more and more cases of poor health and disability in the United States.

07 2008 2009 2010 2011 2012 2013 2014

0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2

2.2 2.2 2.0 2.1 2.2 2.2 2.2 2.1

0.2 21.1 19.4 19.8 19.2 17.9 18.1 19.6

5.8 192.5 179.1 184.5 183.9 175.4 171.6 185.6

8.7 1002.2 945.3 987.1 967.1 936.1 929.5 1006.8

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373342

5. Caregiving

Caregiving refers to attending to another person’s health needs. Caregiving often includes assistance with one or more activities of daily living (ADLs), such as bathing and dressing, as well as multiple instrumental activities of daily living (IADLs), such as paying bills, shopping and transportation [231,232]. Caregivers also provide emotional support to people with Alzheimer’s. More than 15 million Americans provide unpaid care for people with Alzheimer’s or other dementias.

A16 In addition to providing descriptive

information, this section compares caregivers of people with dementia to either caregivers of people with other medical conditions, or if that comparison is not available, to non-caregivers of similar ages and other characteristics.

5.1. Unpaid caregivers

Eighty-three percent of the help provided to older adults in the United States comes from family members, friends or other unpaid caregivers [233]. Nearly half of all caregivers (46 percent) who provide help to older adults do so for some- one with Alzheimer’s or another dementia [234]. In 2016, caregivers of people with Alzheimer’s or other dementias provided an estimated 18.2 billion hours of informal (that is, unpaid) assistance, a contribution to the nation valued at $230.1 billion. This is approximately 48 percent of the revenue of Walmart in 2016 ($482 billion) [235] and nine times the total revenue of McDonald’s in 2015 ($25.4 billion) [236]. The value of informal care (not including caregivers’ out-of-pocket costs) was nearly equal to the costs of direct medical and long-term care of dementia in 2010 [237].

The three primary reasons caregivers provide care and assistance to a person with Alzheimer’s are (1) the desire to keep a family member or friend at home (65 percent), (2) proximity to the person with dementia (48 percent) and (3) the caregiver’s perceived obligation as a spouse or partner (38 percent).A17 Individuals with dementia living in the community are more likely than older adults without dementia to rely on multiple unpaid caregivers; 30 percent of older adults with dementia rely on three or more caregivers, whereas 23 percent of older adults without dementia rely on three or more unpaid caregivers [238]. Only a small percentage of older adults with dementia do not receive help from family members or other informal care providers (8 percent). Of these individuals, more than 40 percent live alone, perhaps making it more difficult to ask for and receive informal care [238].

5.1.1. Who are the caregivers? Several sources have examined the demographic back-

ground of family caregivers of people with Alzheimer’s or other dementias in the United States [239–242].A17 About one in three caregivers (34 percent) is age 65 or older.A17

Over two-thirds of caregivers are married, living with a partner or in a long-term relationship [240].A17 More than two-thirds

of caregivers are non-Hispanic white [239,240,243],A17 while 10 percent are African-American, 8 percent are Hispanic, and 5 percent are Asian.A17 Approximately 40 percent of dementia caregivers have a college degree or greater education [240,243].A17 Forty-one percent of caregivers have a house- hold income of $50,000 or less.A17 Among primary caregivers (individuals who indicate having the most responsibility for helping their relatives) of people with dementia, over half take care of their parents [156,242,243]. Most caregivers (66 percent) live with the care recipient in the community [238]. It is estimated that 250,000 children and young adults between ages 8 and 18 provide help to someone with Alzheimer’s or another dementia [244]. National surveys have found that approximately one quarter of dementia caregivers are “sandwich generation” caregivers—meaning that they care not only for an aging parent, but also for children under age 18 [156,243].A17

5.1.2. Caregiving and women The responsibilities of caring for someone with dementia

often fall to women. Approximately two-thirds of caregivers are women [239,240].A17 More specifically, over one-third of dementia caregivers are daughters [233,238]. It is more common for wives to provide informal care for a husband than vice versa [245]. On average, female caregivers spend more time caregiving than male caregivers [238]. According to the 2014 Alzheimer’s Association Women and Alzheimer’s Poll, of those providing care for 21 to more than 60 hours per week, 67 percent were women and 33 percent were men [246]. The 2015 Behavioral Risk Fac- tor Surveillance System (BRFSS) survey found that of all dementia caregivers who spend more then 40 hours per week providing care, 69 percent were women [156]. Two and a half times as many women as men reported living with the person with dementia full time [246]. Of those providing care to someone with dementia for more than 5 years, 63 percent are women and 37 percent are men [156]. Similarly, caregivers who are women may experience higher levels of burden, depression and impaired health than men, with evidence suggesting that these differences arise because female caregivers tend to spend more time care- giving, to take on more caregiving tasks, and to care for someone with more cognitive, functional and/or behavior problems [247]. Women caregivers are also more likely than men to indicate a need for individual counseling, respite care and support groups [156].

5.1.3. Caregiving tasks The care provided to people with Alzheimer’s or

other dementias is wide-ranging and in some instances all-encompassing. Table 7 summarizes some of the most common types of dementia care provided.

Though the care provided by family members of people with Alzheimer’s or other dementias is somewhat similar to the help provided by caregivers of people with other condi- tions, dementia caregivers tend to provide more extensive

Table 7

Dementia caregiving tasks

Helping with instrumental activities of daily living (lADLs), such as household chores, shopping, preparing meals, providing transportation, arranging for

doctor’s appointments, managing finances and legal affairs, and answering the telephone.

Helping the person take medications correctly, either via reminders or direct administration of medications.

Helping the person adhere to treatment recommendations for dementia or other medical conditions.

Assisting with personal activities of daily living (ADLs), such as bathing, dressing, grooming and feeding and helping the person walk, transfer from bed to

chair, use the toilet and manage incontinence.

Managing behavioral symptoms of the disease such as aggressive behavior, wandering, depressive mood, agitation, anxiety, repetitive activity and nighttime

disturbances.

Finding and using support services such as support groups and adult day service programs.

Making arrangements for paid in-home, nursing home or assisted living care.

Hiring and supervising others who provide care.

Assuming additional responsibilities that are not necessarily specific tasks, such as:

� Providing overall management of getting through the day. � Addressing family issues related to caring for a relative with Alzheimer’s disease, including communication with other family members about care plans, decision-making and arrangements for respite for the main caregiver.

Managing other health conditions (i.e., “comorbidities”), such as arthritis, diabetes or cancer.

Providing emotional support and a sense of security.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 343

assistance. Family caregivers of people with dementia are more likely to monitor the health of their care recipients than are caregivers of people without dementia (79 percent versus 66 percent) [248]. Data from the 2011 National Health and Aging Trends Study [239,249] indicated that caregivers of people with dementia are more likely than caregivers of people without dementia to provide help with self-care and mobility (85 percent versus 71 percent) and health or medical care (63 percent versus 52 percent). Seventy-seven percent of older adults with dementia receive informal assistance with at least one ADL or household activity in contrast to only 20 percent of older adults without dementia; nearly 40 percent of people with dementia receive informal help with three or more ADLs compared with 14 percent of people without de- mentia [238]. Figure 7 illustrates how family caregivers of people with dementia are more likely than caregivers of other older people to assist with ADLs. Over half of individuals with dementia (53 percent) receive assistance from family

Fig. 7. Proportion of caregivers of people with Alzheimer’s or other dementias ver

of daily living, United States, 2015. Created from data from National Alliance fo

members or other informal caregivers for ADLs compared with 11 percent of older adults without dementia [238].

In addition to assisting with ADLs, more caregivers of people with Alzheimer’s or other dementias advocate for their care recipient with community agencies and care pro- viders (65 percent) and manage finances (68 percent) compared with caregivers of people without dementia (46 percent and 50 percent) [243]. More caregivers of people with Alzheimer’s or other dementias arrange for outside services (46 percent) and communicate with health care professionals (80 percent) compared with caregivers of people without dementia (27 percent and 59 percent) [243]. Caregivers of people with dementia are more likely to coordinate health care for the care recipient than caregivers of people without dementia (86 percent versus 72 percent) [234,239]. One in five caregivers of people with Alzheimer’s or other dementias (22 percent) report problems dealing with a bank or credit union when

sus caregivers of other older people who provide help with specific activities

r Caregiving and AARP [243].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373344

helping with the care recipient’s finances, compared with 9 percent of caregivers of people without dementia [243]. Caring for a person with dementia also means managing symptoms that caregivers of people with other diseases may not face, such as neuropsychiatric symptoms (for example, anxiety, apathy and lack of inhibition) and severe behavioral problems. For example, family caregivers of people with Alzheimer’s or other dementias are more likely than family caregivers of people without dementia to help with emotional or mental health problems (41 percent versus 16 percent) and behavioral issues (15 percent versus 4 percent) [243].

When a person with Alzheimer’s or another dementia moves to an assisted living residence or nursing home, the help provided by his or her family caregiver usually changes from the comprehensive care summarized in Table 7 to providing emotional support, interacting with facility staff and advocating for appropriate care. However, some family caregivers continue to help with bathing, dressing and other ADLs [250–252].

5.1.4. Duration of caregiving Eighty-six percent of dementia caregivers have provided

care and assistance for at least the past year, according to the national 2014 Alzheimer’s Association Women and Alz- heimer’s Poll (which surveyed both men and women).A17

Fifty-four percent of caregivers of people with Alzheimer’s or other dementias have provided care for two years or more, compared with 50 percent of caregivers of older adults with other conditions [156]. Caregivers of people with Alzheimer’s or other dementias provide care for a longer time, on average, than caregivers of older adults with other conditions. Well over half (57 percent) of family caregivers of people with Alzheimer’s or other dementias in the community had provided care for 4 or more years. As shown in Figure 8, this percentage increases to 74 percent for family caregivers of people with dementia living in residential care settings compared with 53 percent for family caregivers of

Fig. 8. Proportion of Alzheimer’s and dementia caregivers versus caregivers of oth

States, 2011. Created from data from the National Health and Aging Trends Stud

people with other conditions [238]. More than six in 10 (63 percent) Alzheimer’s caregivers expect to continue having care responsibilities for the next 5 years compared with less than half of caregivers of people without dementia (49 percent) [243].

5.1.5. Hours of unpaid care and economic value of caregiving

In 2016, the 15.9 million family and other unpaid care- givers of people with Alzheimer’s or other dementias pro- vided an estimated 18.2 billion hours of unpaid care. This number represents an average of 21.9 hours of care per care- giver per week, or 1139 hours of care per caregiver per year.A18 With this care valued at $12.65 per hour,A19 the esti- mated economic value of care provided by family and other unpaid caregivers of people with dementia across the United States was $230.1 billion in 2016. Table 8 shows the total hours of unpaid care as well as the value of care provided by family and other unpaid caregivers for the United States and each state. Unpaid caregivers of people with Alzheimer’s or other dementias provided care valued at more than $4 billion in each of 21 states. Unpaid caregivers in each of the four most populous states—California, Florida, New York and Texas—provided care valued at more than $14 billion. A longitudinal study of the monetary value of family caregiving for people with dementia found that the overall value of daily family care increased 18 percent with each additional year of providing care, and that the value of this care increased as the care recipient’s cognitive abilities declined [253]. A study based on the same data source found that the estimated economic value of daily family caregiving costs were lower in situations in which caregivers felt closer in their relationship with the person with dementia [254]. Additional research is needed to estimate the future value of family care for people with Alzheimer’s as the U.S. population continues to age.

Caregivers of people with dementia report providing 27 hours more care per month on average (92 hours versus

er older people in residential care settings by duration of caregiving, United

y [238].

Table 8

Number of Alzheimer’s and dementia (A/D) caregivers, hours of unpaid care, economic value of unpaid care and higher health care costs of caregivers by state,

2016*

State

A/D caregivers

(in thousands)

Hours of unpaid care

(in millions)

Value of unpaid care

(in millions of dollars)

Higher health care costs

of caregivers

(in millions of dollars)y

Alabama 303 345 $4359 $188

Alaska 33 38 480 30

Arizona 325 370 4685 176

Arkansas 176 200 2531 108

California 1600 1822 23,043 999

Colorado 244 277 3510 146

Connecticut 177 201 2548 153

Delaware 53 61 770 45

District of Columbia 28 32 405 29

Florida 1100 1253 15,850 785

Georgia 519 591 7478 283

Hawaii 66 75 944 45

Idaho 81 92 1167 46

Illinois 588 670 8470 397

Indiana 335 382 4831 223

Iowa 135 154 1945 93

Kansas 150 171 2168 102

Kentucky 271 308 3901 177

Louisiana 232 264 3341 157

Maine 69 78 988 58

Maryland 291 332 4196 218

Massachusetts 333 380 4803 309

Michigan 511 582 7361 337

Minnesota 251 286 3614 186

Mississippi 206 234 2964 134

Missouri 314 358 4530 218

Montana 49 56 708 33

Nebraska 82 93 1176 58

Nevada 145 165 2093 83

New Hampshire 66 75 954 52

New Jersey 449 511 6465 340

New Mexico 106 121 1531 70

New York 1020 1161 14,691 848

North Carolina 459 523 6614 296

North Dakota 30 35 438 24

Ohio 597 680 8598 421

Oklahoma 223 253 3206 145

Oregon 181 206 2609 119

Pennsylvania 673 766 9693 519

Rhode Island 53 61 766 44

South Carolina 304 347 4385 191

South Dakota 38 43 542 27

Tennessee 430 489 6191 273

Texas 1380 1571 19,876 815

Utah 148 169 2138 74

Vermont 30 34 430 23

Virginia 458 521 6591 286

Washington 335 382 4832 227

West Virginia 107 122 1543 82

Wisconsin 193 219 2775 140

Wyoming 28 32 400 20

U.S. Total 15,975 18,192 $230,127 $10,852

NOTE. Created from data from the 2009 BRFSS, U.S. Census Bureau, Centers for Medicare & Medicaid Services, National Alliance for Caregiving, AARP

and U.S. Department of Labor.A16, A18, A19, A20

*State totals may not add up to the U.S. total due to rounding. y Higher health care costs are the dollar amount difference between the weighted per capita personal health care spending of caregivers and non-caregivers in

each state. A20

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 345

Fig. 9. Proportion of Alzheimer’s and dementia caregivers who report high

to very high emotional and physical stress due to caregiving. Created from

data from the Alzheimer’s Association.A17

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373346

65 hours) than caregivers of people without dementia, with 26 percent providing 41 or more hours of care per week [239,248]. Considering all sources of unpaid care (for example, help from multiple family members), individuals with dementia receive an average of 171 hours of care per month, which is over 100 hours more care per month than those without dementia (66 hours per month, on average) [233].

5.1.6. Impact of Alzheimer’s caregiving Caring for a person with Alzheimer’s or another dementia

poses special challenges. For example, people in the middle to later stages of Alzheimer’s experience losses in judgment, orientation, and the ability to understand and communicate effectively. Family caregivers must often help people with Alzheimer’s manage these issues. The personality and behavior of a person with Alzheimer’s are affected as well, and these changes are often among the most challenging for family caregivers [255–257]. Individuals with Alzheimer’s also require increasing levels of supervision and personal care as the disease progresses. As symptoms worsen, the care required of family members can result in increased emotional stress and depression; new or exacerbated health problems; and depleted income and finances due in part to disruptions in employment and paying for health care or other services for themselves and their care recipients [258–265].A17 Data from the 2016 Alzheimer’s Association Family Impact of Alzheimer’s Survey reported in 2016 Alzheimer’s Disease Facts and Figures indicated that among care contributors (a friend or relative who paid for dementia expenses and/or provided care for someone with dementia at least once a month in the prior year), 48 percent cut back on spending and 43 percent cut back on saving due to the out-of-pocket cost of providing help to someone with dementia [265]. Because of care responsibilities in the year prior to the survey, close to four in 10 care contributors indicated that the “food they bought just didn’t last, and they didn’t have money to get more” and three in 10 ate less because of care-related costs [265].

5.1.6.1. Caregiver emotional and social well-being The intimacy, shared experiences and memories that are

often part of the relationship between a caregiver and care recipient may also be threatened due to the memory loss, functional impairment and psychiatric/behavioral distur- bances that can accompany the progression of Alzheimer’s. Although caregivers report positive feelings about caregiving, such as family togetherness and the satisfaction of helping others [266–269],A17 they also report high levels of stress when providing care:

� Based on the Level of Care Index that combined the number of hours of care and the number of ADL tasks performed by the caregiver, more dementia caregivers in the 2015 NAC/AARP survey were classified as hav- ing a high level of burden than caregivers of people without dementia (46 percent versus 38 percent) [243].

� Compared with caregivers of people without dementia, twice as many caregivers of those with dementia indicate substantial emotional, financial and physical difficulties [239].

� Fifty-nine percent of family caregivers of people with Alzheimer’s or other dementias rated the emotional stress of caregiving as high to very high (Figure 9).A17 Nearly half of dementia caregivers indicate that providing help is highly stressful (49 percent) compared with 35 percent of caregivers of people without dementia [243].

� Many caregivers of people with Alzheimer’s or other dementias provide help alone. Forty-one percent of dementia caregivers in the 2014 Alzheimer’s Association poll reported that no one else provided unpaid assistance.A17

5.1.6.1.1. Depression and Mental Health

� Approximately 30 percent to 40 percent of family caregivers of people with dementia suffer from depression, compared with 5 percent to 17 percent of non-caregivers of similar ages [262,270–274].

� The prevalence of depression is higher among dementia caregivers than other caregivers such as those who provide help to individuals with schizophrenia (20 percent) or stroke (19 percent) [274–276].

� Depression risk increases alongside the worsening cognitive symptoms of the person with dementia [274,277,278].

� In a recent meta-analysis, kin relationship was the strongest predictor of caregiver depression; caregivers of spouses had two and a half times higher odds of having depression as caregivers of people who were not spouses [274].

� The prevalence of anxiety among dementia caregivers is 44 percent, which is higher than among caregivers of people with stroke (31 percent) [274,276].

� Caregivers of individuals with Alzheimer’s report more subjective cognitive problems (e.g., memory

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 347

complaints) and experience greater declines in cognition over time than non-caregivers matched for age and other characteristics [279,280].

5.1.6.1.2. Strain

� Twice as many caregivers of people with Alzheimer’s or other dementias have difficulty with medical/ nursing-related tasks (e.g., injections, tube feedings, catheter/colostomy care) as caregivers of individuals without dementia (22 percent compared with 11 percent) [248].

� Half of caregivers (51 percent) of people with Alzheimer’s or other dementias indicate having no experience performing medical/nursing-related tasks [248], and they often lack the information or resources necessary to manage complex medication regimens [281,282].

� According to the 2014 Alzheimer’s Association poll of caregivers, respondents often believed they had no choice in taking on the role of caregiver.A17

� The poll also found that women with children under age 18 felt that caregiving for someone with Alzheimer’s was more challenging than caring for children (53 percent).A17

� Sandwich generation caregivers indicate lower quality of life and diminished health and health behaviors (for example, less likely to choose healthful foods and less likely to exercise) compared with non- sandwich generation caregivers or non-caregivers [264,283–285].

5.1.6.1.3. Stress of care transitions

� Admitting a relative to a residential care facility has mixed effects on the emotional and psychological well-being of family caregivers. Some studies suggest that distress remains unchanged or even increases after a relative is admitted to a residential care facility, but other studies have found that distress declines following admission [252,286,287].

� The demands of caregiving may intensify as people with dementia approach the end of life [288]. In the year before a care recipient’s death, 59 percent of caregivers felt they were “on duty” 24 hours a day, and many felt that caregiving during this time was extremely stressful [289]. One study of end-of-life care found that 72 percent of family caregivers experienced relief when the person with Alzheimer’s or another dementia died [289].

5.1.6.2. Caregiver physical health For some caregivers, the demands of caregiving may

cause declines in their own health. Evidence suggests that the stress of providing dementia care increases care- givers’ susceptibility to disease and health complications

[290]. As shown in Figure 9, 38 percent of Alzheimer’s and dementia caregivers indicate that the physical stress of caregiving is high to very high.A17 Nearly three in 10 caregivers of people with Alzheimer’s or other dementias report that providing care results in high physical strain (29 percent) compared with 17 percent of caregivers of people without dementia [243]. Sleep disturbances, which can occur frequently when caring for a relative with Alzheimer’s or another dementia, have also been shown to negatively influence family caregivers’ health [291,292].

5.1.6.2.1. General health Seventy-four percent of caregivers of people with

Alzheimer’s or other dementias reported that they were “somewhat concerned” to “very concerned” about maintain- ing their own health since becoming a caregiver.A17 Forty- two percent of caregivers of people with Alzheimer’s or another dementia report that their health is excellent or very good, which is lower than caregivers of people without dementia (50 percent) [243]. In addition, over 1 in 3 caregivers of people with Alzheimer’s or another dementia report that their health has gotten worse due to care responsibilities (35 percent) compared with 19 percent of caregivers of people without dementia [243]. Dementia care- givers indicated lower health-related quality of life than non- caregivers and were more likely than non-caregivers to report that their health was fair or poor [260,264,293,294]. Dementia caregivers were also more likely than caregivers of other older people to say that caregiving made their health worse [295]. Data from the Health and Retirement Study showed that dementia caregivers who provided care to spouses were much more likely (41 percent increased odds) than other spousal caregivers to become increasingly frail during the time between becoming a caregiver and their spouse’s death, accounting for differences in age and addi- tional factors [296]. Other studies, however, suggest that caregiving tasks have the positive effect of keeping older caregivers more physically active than non-caregivers [297].

5.1.6.2.2. Physiological changes The chronic stress of caregiving is associated with phys-

iological changes that could increase the risk of developing chronic conditions. For example, several studies found that under certain circumstances some Alzheimer’s caregivers were more likely to have elevated biomarkers of cardiovas- cular disease risk and impaired kidney function risk than those who were not caregivers [298–303].

Caregivers of a spouse with Alzheimer’s or another de- mentia are more likely than married non-caregivers to have physiological changes that may reflect declining physical health, including high levels of stress hormones [304], reduced immune function [258,305], slow wound healing [306], coronary heart disease [307], impaired function of the endothelium (the inner lining of blood vessels) and increased incidence of hypertension [308].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373348

Some of these changes may be associated with an increased risk of cardiovascular disease [309].

5.1.6.2.3. Health care The physical and emotional impact of dementia

caregiving is estimated to have resulted in $10.9 billion in health care costs in the United States in 2016.A20 Table 8 shows the estimated higher health care costs for caregivers of people with Alzheimer’s or other dementias in each state. In separate studies, hospitalization and emergency depart- ment visits were more likely for dementia caregivers who helped care recipients who were depressed, had low func- tional status or had behavioral disturbances [264,310,311]. Increased depressive symptoms among caregivers over time are also linked to more frequent doctor visits, a higher number of outpatient tests and procedures, and greater use of over-the-counter and prescription medications [311].

5.1.6.2.4. Mortality The health of a person with dementia may also affect the

caregiver’s risk of dying, although studies have reported mixed findings. In one study, caregivers of spouses who were hospitalized and had dementia in their medical records were more likely to die in the following year than caregivers whose spouses were hospitalized but did not have dementia, even after accounting for the age of caregivers [312]. One study found that caregivers who perceive higher strain due to care responsibilities are at higher risk for death than caregivers who perceive little or no strain [313].

5.1.6.3. Caregiver employment Six in 10 caregivers of people with Alzheimer’s or

another dementia were employed in the past year while providing help [243]. These individuals worked an average of 35 hours per week while caregiving [243]. Among people who were employed in the past year while providing care to someone with Alzheimer’s or another dementia, 15 percent

Fig. 10. Work-related changes among caregivers of people with Alzheimer’s and

giving. Created from data from the National Alliance for Caregiving and AARP [

quit their jobs or retired early due to their care responsibil- ities. Fifty-seven percent reported sometimes needing to go in late or leave early, and 16 percent had to take a leave of absence. Other work-related challenges for dementia and non-dementia caregivers who had been employed in the past year are summarized in Figure 10 [243].

5.1.7. Interventions designed to assist caregivers For more than 30 years, strategies to support family care-

givers of people with Alzheimer’s have been developed and evaluated. The types and focus of these strategies (often called “interventions”) are summarized in Table 9 [262,263].

In general, the goal of interventions is to improve the health and well-being of dementia caregivers by relieving the negative aspects of caregiving. Some also aim to delay nursing home admission of the person with dementia by providing caregivers with skills and resources (emotional, social and psychological) to continue helping their relatives or friends at home. Specific approaches used in various interventions include providing education to caregivers, helping caregivers manage dementia-related symptoms, improving social support for caregivers and providing caregivers with respite from caregiving duties.

According to a recent publication on dementia caregiver interventions that reviewed seven meta-analyses and 17 systematic reviews of randomized controlled trials, the following characteristics distinguish interventions that are effective: family caregivers are actively involved in the inter- vention, in contrast to passively receiving information; the intervention is tailored and flexible to meet the changing needs of family caregivers during the course of a relative’s dementia; and the intervention meets the needs not only of caregivers, but of care recipients as well [314]. A 2012 report identified 44 interventions that have been shown by random- ized controlled trials conducted in the United States to have benefits for individuals with Alzheimer’s or other dementias

other dementias who had been employed at any time since they began care-

243].

Table 9

Type and focus of caregiver interventions

Type of intervention Description

Case management Provides assessment, information, planning, referral, care coordination and/or advocacy for family caregivers.

Psychoeducational

approaches

Include a structured program that provides information about the disease, resources and services, and about how to expand skills

to effectively respond to symptoms of the disease (that is, cognitive impairment, behavioral symptoms and care-related needs).

Include lectures, discussions and written materials and are led by professionals with specialized training.

Counseling Aims to resolve pre-existing personal problems that complicate caregiving to reduce conflicts between caregivers and care

recipients and/or improve family functioning.

Support groups Less structured than psychoeducational or psychotherapeutic interventions, support groups provide caregivers the opportunity to

share personal feelings and concerns to overcome feelings of social isolation.

Respite Provides planned, temporary relief for the caregiver through the provision of substitute care; examples include adult day services

and in-home or institutional respite for a certain number of weekly hours.

Psychotherapeutic

approaches

Involve the establishment of a therapeutic relationship between the caregiver and a professional therapist (for example, cognitive-

behavioral therapy for caregivers to focus on identifying and modifying beliefs related to emotional distress, developing new

behaviors to deal with caregiving demands, and fostering activities that can promote caregiver well-being).

Multicomponent

approaches

Are characterized by intensive support strategies that combine multiple forms of interventions, such as education, support and

respite into a single, long-term service (often provided for 12 months or more).

NOTE. Created from data from Pinquart and colleagues and S€orensen and colleagues [262,263].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 349

as well as their family caregivers, and more evaluations are emerging each year [315,316].

Interventions for dementia caregivers that have demonstrated efficacy in scientific evaluations have been gradually implemented in the community [317–328]. These implementation efforts are generally successful at improving how caregiver services are delivered, and they have the potential to reach a large number of families while also helping caregivers cope with their responsibilities. Similar efforts have attempted to broaden the reach and accessibility of interventions for dementia caregivers through the use of technologies (for instance, video-phone delivery and online training) and have shown some success [329–331]. However, more work is needed to ensure that interventions for dementia caregivers are available and accessible to those who need them. Because caregivers and the settings in which they provide care are diverse, more studies are required to define which interventions are most effective for specific situations [332–334]. Improved tools to “personalize” services for caregivers to maximize their benefits represent an emerging area of research [335–338]. More studies are also needed to explore the effectiveness of interventions in different racial, ethnic and socioeconomic groups and in various geographic settings [330,339–345].

5.2. Paid caregivers

5.2.1. Direct care workers for people with Alzheimer’s or other dementias

Direct-care workers, such as nurse aides, home health aides and personal and home care aides, provide most of the paid long-term care to older adults living at home or

in residential settings [346]. In nursing homes, nursing assistants make up the majority of staff who work with cognitively impaired residents [347–349]. Nursing assistants help with bathing, dressing, housekeeping, food preparation and other activities. Most nursing assistants are women, and they come from increasingly diverse ethnic, racial and geographic backgrounds.

Direct-care workers have difficult jobs, and they may not receive the training necessary to provide dementia care [348,350]. One review found that direct-care workers received, on average, 75 hours of training and that this training included little focus on issues specific or pertinent to dementia care [348]. Turnover rates are high among direct-care workers, and recruitment and retention are persistent challenges [351]. Inadequate education and challenging work environments have also contributed to higher turnover rates among nursing staff across care environments [352]. Studies have shown that staff training programs to improve the quality of dementia care in nursing homes and hospitals have modest benefits [350,353–357].

5.2.2. Shortage of geriatric health care professionals in the United States

Professionals who may receive special training in caring for older adults include physicians, nurse practitioners, registered nurses, social workers, pharmacists, physician assistants and case workers [351]. It is estimated that the United States has approximately half the number of certified geriatricians that it currently needs [358]. As of 2014, there were 7428 certified geriatricians and 1629 geriatric psychiatrists in the United States, or one geriatrician and one geriatric psychiatrist for every 2526 and 11,526 Americans age 75 or older, respectively [359]. The

Fig. 11. Aggregate cost of care by payment source for Americans age 65

and older with Alzheimer’s or other dementias, 2017. Data are in 2017 dol-

lars. Created from data from the Lewin Model. A21

“Other” payment sources

include private insurance, health maintenance organizations, other managed

care organizations and uncompensated care.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373350

American Geriatrics Society estimates that, due to the increase in older Americans and the stagnation in the number of new geriatric professionals trained in the past decade, this differential will increase to one geriatrician and one geriatric psychiatrist for every 4484 and 20,448 older Americans, respectively, by 2030 [359]. Less than 1 percent of registered nurses, physician assistants and pharmacists identify themselves as specializing in geriatrics [351]. Similarly, although 73 percent of social workers serve clients age 55 and older, only 4 percent have formal certification in geriatric social work [351]. Furthermore, the overall aging of the long-term care workforce may affect the number of paid caregivers [352].

5.2.3. Enhancing health care for family caregivers There is a growing consensus that primary care providers

of people with Alzheimer’s should acknowledge the presence of caregivers and assess their well-being to improve the overall management of the person with demen- tia [360–363]. Recognizing that the complex care challenges of people with dementia also require interprofessional collaboration and education [363–365], ongoing efforts have attempted to integrate innovative care management practices with traditional primary care for people with dementia [366–369]. One example involves a skilled professional who serves as the care “manager” of the person with dementia. The care manager collaborates with primary care physicians and nurse practitioners to develop personalized care plans. These plans can provide support to family caregivers, help people with dementia manage care transitions (for example, a change in care provider or site of care), and ensure the person with dementia has access to appropriate community-based services. Other models include addressing the needs of family caregivers simultaneously with comprehensive disease management of the care recipient to improve the quality of life of both family caregivers and people with dementia in the community [370]. Several evaluations have suggested that such approaches have considerable potential for improving outcomes for people with dementia and their family caregivers (for example, delayed nursing home admission and reduction in caregiver distress) [371–375]. Current research is attempting to determine the feasibility of these models beyond the specialty settings in which they currently operate [376,377].

In 2016, the National Academies of Sciences, Engineer- ing, and Medicine released Families Caring for an Aging America, a seminal report that includes a number of recommendations to refocus national health care reform efforts from models of care that center on the patient (person-centered care) to models of care that also explicitly engage and support the patient’s family (person- and family-centered care). [378] These service models recognize the important role family members play in providing care and incorporate family caregivers during the delivery of health care to relatives with dementia. Furthermore, these

models encourage health care providers to deliver evidence-based services and support to both caregivers and care recipients [378,379].

6. Use and costs of health care, long-term care and hospice

The costs of health care and long-term care for individ- uals with Alzheimer’s or other dementias are substantial, and dementia is one of the costliest conditions to society [237]. Total payments in 2017 (in 2017 dollars) for all individuals with Alzheimer’s or other dementias are esti- mated at $259 billion (Figure 11). Medicare and Medicaid are expected to cover $175 billion, or 67 percent, of the total health care and long-term care payments for people with Alzheimer’s or other dementias. Out-of-pocket spending is expected to be $56 billion, or 22 percent of total payments.A21 Throughout the rest of this section, all costs are reported in 2016 dollars unless otherwise indicated.A22

6.1. Total cost of health care and long-term care

Table 10 reports the average annual per-person payments for health care and long-term care services for Medicare beneficiaries age 65 and older with and without Alzheimer’s or other dementias. Total per-person health care and long-term care payments in 2016 from all sources for Medicare beneficiaries with Alzheimer’s or other dementias were over three times as great as payments for other Medicare beneficiaries in the same age group ($46,786 per person for those with dementia compared with $13,351 per person for those without dementia) [380].A23

Twenty-seven percent of older individuals with Alzheimer’s or other dementias who have Medicare also have Medicaid coverage, compared with 11 percent of individuals without dementia [380]. Medicaid pays for nursing home and other long-term care services for some people with very low income and low assets, and the high

Table 10

Average annual per-person payments for health care and long-term care

services, Medicare beneficiaries age 65 and older, with and without

Alzheimer’s or other dementias, in 2016 dollars

Payment source

Beneficiaries with

Alzheimer’s or other

dementias

Beneficiaries without

Alzheimer’s or other

dementias

Medicare $23,497 $7223

Medicaid 8182 349

Uncompensated 364 365

Health maintenance

organization

1205 1475

Private insurance 2152 1358

Other payer 895 231

Out of pocket 10,315 2232

Total* $46,786 $13,351

NOTE. Created from unpublished data from the Medicare Current Bene-

ficiary Survey for 2011 [380]

*Payments from sources do not equal total payments exactly due to the

effect of population weighting. Payments for all beneficiaries with Alz-

heimer’s and other dementias include payments for community-dwelling

and facility-dwelling beneficiaries.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 351

use of these services by people with dementia translates into high costs for the Medicaid program. Average annual Medicaid payments per person for Medicare beneficiaries with Alzheimer’s or other dementias ($8182) were 23 times as great as average Medicaid payments for Medicare beneficiaries without Alzheimer’s or other dementias ($349) (Table 10) [380].

Despite these and other sources of financial assistance, in- dividuals with Alzheimer’s or other dementias still incur high out-of-pocket costs. These costs are for Medicare and other health insurance premiums and for deductibles, copayments and services not covered by Medicare, Medicaid or additional sources of support. On average, Medicare beneficiaries age 65 and older with Alzheimer’s or other dementias paid $10,315 out of pocket annually for health care and long-term care services not covered by other sources (Table 10) [380].

Researchers have evaluated the additional or “incremen- tal” health care, long-term care and caregiving costs of de- mentia (that is, the costs specifically attributed to dementia when comparing people with and without dementia who have the same coexisting medical conditions and demographic characteristics) [237,381]. One group of researchers found that the incremental health care and nursing home costs for those with dementia were $28,501 per person per year in 2010 dollars ($32,924 in 2016 dollars) [237].A22, A24 Another group of researchers found that the incremental lifetime cost of Alzheimer’s dementia was substantially higher for women than men, due to a greater lifetime risk of developing Alzheimer’s dementia [382]. Additionally, because women are more likely to be widowed and living in poverty, the incremental Medicaid costs associated with Alzheimer’s dementia were 70 percent higher for women than men.

Other researchers compared end-of-life costs for individuals with and without dementia and found that the

total cost in the last 5 years of life was $287,038 per person in 2010 dollars for people with dementia and $183,001 per person without dementia but with other conditions ($341,651 and $217,820 respectively, in 2016 dollars), a difference of 57 percent [383]. Additionally, out-of-pocket costs represented a substantially larger proportion of total wealth for those with dementia than for people without dementia (32 percent versus 11 percent).

6.2. Use and costs of health care services

6.2.1. Use of health care services People with Alzheimer’s or other dementias have twice as

many hospital stays per year as other older people [188]. Moreover, the use of health care services by people with other serious medical conditions is strongly affected by the presence or absence of dementia. In particular, people with coronary artery disease, diabetes, chronic kidney disease, chronic obstructive pulmonary disease (COPD), stroke or cancer who also have Alzheimer’s or other dementias have higher use and costs of health care services than people with these medical conditions but no coexisting dementia.

In addition to having more hospital stays, older peoplewith Alzheimer’s or other dementias have more skilled nursing fa- cility stays and home health carevisits than other older people.

� Hospital. There are 538 hospital stays per 1000 Medicare beneficiaries age 65 and older with Alzheimer’s or other dementias compared with 266 hospital stays per 1000 Medicare beneficiaries age 65 and older without these conditions [188]. A person with dementia in 2012 had, on average, 22.5 inpatient days—defined as days in a hospital or skilled nursing facility—compared with 4.6 days for the Medicare pop- ulation as a whole [384]. The most common reasons for hospitalization of people with Alzheimer’s dementia are syncope (fainting), fall and trauma (26 percent); ischemic heart disease (17 percent); and gastrointestinal disease (9 percent) (Figure 12) [385]. In a study of inpa- tient hospitalizations of adults age 60 and older, those with Alzheimer’s were at 7 percent greater risk of dying during the hospital stay and stayed nearly a day longer than individuals without Alzheimer’s dementia [386].

� Skilled nursing facility. Skilled nursing facilities provide direct medical care that is performed or supervised by registered nurses, such as giving intravenous fluids, changing dressings and adminis- tering tube feedings [387]. There are 283 skilled nursing facility stays per 1000 beneficiaries with Alzheimer’s or other dementias compared with 73 stays per 1000 beneficiaries for people without these conditions—a rate nearly four times as great [188].

� Home health care. Twenty-five percent of Medicare beneficiaries age 65 and older with Alzheimer’s or

Fig. 12. Reasons for hospitalization of individuals with Alzheimer’s dementia: Percentage of hospitalized individuals by admitting diagnosis. All hospitaliza-

tions for individuals with a clinical diagnosis of probable or possible Alzheimer’s were used to calculate percentages. The remaining 37 percent of hospital-

izations were due to other reasons. Created from data from Rudolph and colleagues [385].

Tab

Av

ser

wit

Ser

Inp

Me

Ski

Nu

Ho

Ho

Pre

N

fici

*

ora y

for

hom

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373352

other dementias have at least one home health care visit during the year, compared with 10 percent of Medicare beneficiaries age 65 and older without Alzheimer’s or other dementias [188].

6.2.2. Costs of health care services Average per-person payments for health care services

(hospital, physician and other medical provider, nursing home, skilled nursing facility, hospice and home health care) and prescription medications were higher for Medicare beneficiaries with Alzheimer’s or other dementias than for other Medicare beneficiaries in the same age group (Table 11) [380].

6.2.3. Use and costs of health care services across the spectrum of cognitive impairment

Health care costs increase with the presence of dementia. In a population-based study of adults ages 70 to 89 in

le 11

erage annual per-person payments for health care and long-term care

vices provided to Medicare beneficiaries age 65 and older, with and

hout Alzheimer’s or other dementias, in 2016 dollars

vice

Beneficiaries

with Alzheimer’s

or other dementias

Beneficiaries

without Alzheimer’s

or other dementias

atient hospital $10,415 $3364

dical provider* 6031 3757

lled nursing facility 6547 448

rsing home 14,999 726

spice 1966 149

me health care 2461 357

scription medicationsy 3318 2846

OTE. Created from unpublished data from the Medicare Current Bene-

ary Survey for 2011 [380].

“Medical provider” includes physician, other medical provider and lab-

tory services, and medical equipment and supplies.

Information on payments for prescription medications is only available

people who were living in the community, that is, not in a nursing

e or assisted living facility.

Olmsted County, Minnesota, annual health care costs were significantly higher for individuals with newly diagnosed dementia and existing dementia than for those with normal cognition, and significantly higher for individuals with existing dementia than those with mild cognitive impairment (MCI) [388]. Annual health care costs for individuals with MCI were not significantly different, however, from costs for individuals with normal cognition.

Several groups of researchers have found that health care and prescription drug spending is significantly higher in the year prior to diagnosis [389–391] and two years prior to diagnosis [392] compared with otherwise similar individuals not diagnosed with Alzheimer’s or another dementia, although there is less agreement about the sources of increased spending. In one study, the largest differences were in inpatient and post-acute care [390], while in another study the differences in spending were primarily due to outpatient care, home care and medical day services [391]. In a third study, the differences were due to home health care, skilled nursing care and durable medical equipment [392]. Two groups of researchers have found that spending in the year after diagnosis continued to be higher than for individuals not diagnosed with the disease, ranging from $9333 in 2011 dollars ($10,781 in 2016 dollars) [389] to $17,852 in 2014 dollars ($18,961 in 2016 dollars) [390]. One group of researchers found no difference in health care spending in the two years after diagnosis [392]. Researchers have found that time to Alzheimer’s dementia diagnosis after the earliest diagnosis of cognitive decline was shorter for individuals whose cognitive impairment was diagnosed by a specialist (that is, neurologist, psychiatrist or geriatrician) than those diagnosed by a non-specialist. Additionally, individuals diagnosed with cognitive impairment by a specialist had lower Medicare costs in the year after receiving a diagnosis of Alzheimer’s dementia than those diagnosed by a non-specialist [393]. While more research is needed to

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 353

understand the underlying causes of increased use of health care services immediately prior to and after receiving a diagnosis of Alzheimer’s dementia, it may be attributed to care for disability and injuries, such as falls, that might result from the early stage of the disease [394]; treatments related to cognitive impairment or coexisting medical con- ditions; the timing of receiving an Alzheimer’s diagnosis; and costs of diagnostic procedures.

6.2.4. Impact of Alzheimer’s and other dementias on use and costs of health care in people with coexisting medical conditions

Medicare beneficiaries with Alzheimer’s or other demen- tias are more likely than those without dementia to have other chronic conditions [188]. While 26 percent of Medicare beneficiaries age 65 and older with Alzheimer’s or other dementias have five or more chronic conditions (including Alzheimer’s or other dementias), only 3.8 percent of Medi- care beneficiaries without Alzheimer’s or other dementias have five or more chronic conditions [188]. Table 12 reports the proportion of people with Alzheimer’s or other dementias who have certain coexisting medical conditions. In 2013, 38 percent of Medicare beneficiaries age 65 and older with dementia also had coronary artery disease, 37 percent also had diabetes, 29 percent also had chronic kidney disease, 28 percent also had congestive heart failure and 25 percent also had chronic obstructive pulmonary disease [188].

Medicare beneficiaries who have Alzheimer’s or other dementias and a serious coexisting medical condition have higher average per-person payments for most health care services than Medicare beneficiaries who have the same medical condition without dementia. Table 13 shows the average per-person Medicare payments for seven specific medical conditions among beneficiaries who have Alzheimer’s or other dementias and beneficiaries who do not have Alzheimer’s [188]. Medicare beneficiaries with Alzheimer’s or other dementias had higher average per-person payments in all categories except hospital care payments for individuals with congestive heart failure.

Table 12

Specific coexisting medical conditions among Medicare beneficiaries age

65 and older with Alzheimer’s or other dementias, 2013

Coexisting condition

Percentage of beneficiaries

with Alzheimer’s or other

dementias who also had a

coexisting medical condition

Coronary artery disease 38

Diabetes 37

Chronic kidney disease 29

Congestive heart failure 28

Chronic obstructive pulmonary disease 25

Stroke 22

Cancer 13

NOTE. Created from unpublished data from the National 5% Sample

Medicare Fee-for-Service Beneficiaries for 2013 [188]

6.3. Use and costs of long-term care services

An estimated 58 percent of older adults with Alzheimer’s or other dementias live in the community, compared with 98 percent of older adults without Alzheimer’s or other dementias [380]. Of those with dementia who live in the community, 75 percent live with someone and the remaining 25 percent live alone [380]. As their disease progresses, people with Alzheimer’s or other dementias generally receive more care from family members and other unpaid caregivers. Many people with dementia also receive paid services at home; in adult day centers, assisted living facilities or nursing homes; or in more than one of these settings at different times during the often long course of the disease. The average costs of these services are high (assisted living: $43,539 per year [395] and nursing home care: $82,125 to $92,378 per year) [395], and Medicaid is the only public program that covers the long nursing home stays that most people with dementia require in the late stages of their illnesses.

6.3.1. Use of long-term care services by setting Most people with Alzheimer’s or other dementias who

live at home receive unpaid help from family members and friends, but some also receive paid home- and community-based services, such as personal care and adult day care. A study of older people who needed help to perform daily activities—such as dressing, bathing, shop- ping and managing money—found that those who also had cognitive impairment were more than twice as likely as those who did not have cognitive impairment to receive paid home care [396]. In addition, those who had cognitive impairment and received paid services used almost twice as many hours of care monthly as those who did not have cognitive impair- ment [396].

People with Alzheimer’s or other dementias make up a large proportion of all elderly people who receive adult day services and nursing home care.

� Adult day services. Thirty-two percent of individuals using adult day services have Alzheimer’s or other dementias [397], and 73 percent of adult day service programs offer specific programs for individuals with Alzheimer’s or other dementias [398].

� Assisted living. Forty-two percent of residents in assisted living facilities (that is, housing that includes services to assist with everyday activities, such as medication management and meals) had Alzheimer’s or other dementias in 2010 [399]. Forty percent of res- idents in residential care facilities, including assisted living facilities, have Alzheimer’s or other dementias [400]. Small residential care facilities (4 to 25 beds) have a larger proportion of residents with Alzheimer’s or other dementias than larger facilities (47 percent in facilities with 4 to 25 beds compared with 42 percent in facilities with 26 to 50 beds and 37 percent in facilities with more than 50 beds) [400]. Fifty-eight percent of

Table 13

Average annual per-person payments by type of service and coexisting medical condition for Medicare beneficiaries age 65 and older, with and without

Alzheimer’s or other dementias, in 2016 dollars*

Medical condition by

Alzheimer’s/dementia (A/D) status

Average per-person Medicare payment

Total Medicare

payments Hospital care Physician care

Skilled nursing

facility care Home health care Hospice care

Coronary artery disease

With A/D $26,223 $7853 $2199 $4386 $2343 $3092

Without A/D 16,366 5656 1565 1410 971 374

Diabetes

With A/D 25,385 7472 2154 4242 2267 2590

Without A/D 14,014 4681 1380 1225 844 255

Congestive heart failure

With A/D 28,773 8825 2310 4794 2455 3452

Without A/D 24,412 8960 2075 2596 1742 807

Chronic kidney disease

With A/D 28,002 8457 2255 4666 2319 3075

Without A/D 20,077 6989 1779 1883 1201 473

Chronic obstructive pulmonary disease

With A/D 27,797 8481 2283 4624 2399 3189

Without A/D 18,962 6792 1725 1749 1201 602

Stroke

With A/D 26,608 7751 2177 4564 2254 3199

Without A/D 19,169 6305 1753 2294 1455 605

Cancer

With A/D 25,207 7352 2109 3934 2074 2862

Without A/D 15,987 4833 1447 1050 692 484

NOTE. Created from unpublished data from the National 5% Sample Medicare Fee-for-Service Beneficiaries for 2014 [188].

*This table does not include payments for all kinds of Medicare services, and as a result the average per-person payments for specific Medicare services do not

sum to the total per-person Medicare payments.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373354

residential care facilities offer programs for residents with Alzheimer’s or other dementias [401].

� Nursing home care. Sixty-one percent of nursing home residents in 2014 had moderate or severe cognitive impairment [402]. Nursing home admission by age 80 is expected for 75 percent of people with Alzheimer’s dementia compared with only 4 percent of the general population [218].

� Alzheimer’s special care units. An Alzheimer’s special care unit is a dedicated unit in a nursing home that has tailored services for individuals with Alzheimer’s or other dementias. Nursing homes had a total of 73,742 beds in Alzheimer’s special care units in 2014, a decrease of 3 percent from the previous year [403,404]. These Alzheimer’s special care unit beds accounted for just 4 percent of all nursing home beds, despite 61 percent of nursing home residents having moderate or severe cognitive impairment.

6.3.1.1. Long-term care services provided at home and in the community

Nationally, state Medicaid programs are shifting long-term care services from institutional care to home- and community- based services as a means to both reduce unnecessary costs and meet the growing demand for these services by older adults. The federal and state governments share the manage- ment and funding of the program, and states differ greatly in the services covered by their Medicaid programs. Spending

on home care for Medicare beneficiaries with Alzheimer’s or other dementias nearly doubled between 2004 and 2011, although increases in spending may be due to a variety of fac- tors, including more people being diagnosed with Alzheimer’s dementia, more people using home care, more intensive use of home care service and an increase in Medicaid coverage by older adults [380,405]. In 2014, home- and community- based services represented the majority (53 percent) of Medicaid spending on long-term services and supports, with the remaining 47 percent spent for institutional care [406]. More research is needed, however, to understand the extent towhich home- and community-based services meet the needs of individuals with Alzheimer’s or other dementias.

6.3.1.2. Transitions between care settings A recent research study demonstrated that individuals

with dementia often move between a nursing facility, hospital and home, rather than remaining solely in a nursing facility [407]. In this longitudinal study of primary care patients with dementia, researchers found that those discharged from a nursing facility were nearly equally as likely to be discharged home (39 percent) as discharged to a hospital (44 percent). Individuals with dementia may also transition between a nursing facility and hospital or between a nursing facility, home and hospital, creating challenges for caregivers and providers to ensure that care is coordinated across set- tings. Other research has shown that nursing home residents frequently have burdensome transitions at the end of life,

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 355

including admission to an intensive care unit in the last month of life, late enrollment in hospice and receipt of a feeding tube [408]. The number of care transitions for nursing home resi- dents with advanced cognitive impairment varies substan- tially across geographic regions of the United States [409].

6.3.2. Costs of long-term care services Long-term care services include home- and community-

based services, assisted living and nursing home care. The following estimates are for all users of these services.

� Home care. The median cost for a paid non-medical home health aide is $20 per hour and $127 per day [395]. Home care costs have increased by 1.3 percent annually over the past 5 years.

� Adult day centers. The median cost of adult day services is $68 per day [395]. The cost of adult day services has increased by 2.5 percent annually over the past 5 years. Ninety-five percent of adult day centers provide care for people with Alzheimer’s or other dementias, and 2 percent of these centers charged an additional fee for these clients in 2012 [410].

� Assisted living facilities. The median cost for care in an assisted living facility is $3628 per month, or $43,539 per year [395]. The cost of assisted living has increased by 2.2 percent annually over the past 5 years.

� Nursing homes. The average cost for a private room in a nursing home is $253 per day, or $92,378 per year. The average cost of a semi-private room in a nursing home is $225 per day, or $82,125 per year [395]. The cost of nursing home care has increased by 3.5 percent and 3.1 percent annually over the past 5 years for a private and semi-private room, respectively.

6.3.2.1. Affordability of long-term care services Few individuals with Alzheimer’s or other dementias

have sufficient long-term care insurance or can afford to pay out of pocket for long-term care services for as long as the services are needed.

� Income and asset data are not available for people with Alzheimer’s or other dementias specifically, but 50 percent of Medicare beneficiaries have incomes of $24,150 or less and 25 percent have incomes of $14,350 or less (in 2014 dollars) [411].

� Fifty percent of Medicare beneficiaries had total sav- ings of $63,350 or less (in 2014 dollars), 25 percent have savings of $11,900 or less, and 8 percent had no savings or were in debt. Median savings were substan- tially lower for African-American and Hispanic bene- ficiaries than for white Medicare beneficiaries [411].

6.3.2.2. Long-term care insurance Long-term care insurance covers costs of long-term care

services and supports in the home, in the community and in residential facilities. Long-term care insurance typically covers care provided in a nursing home, assisted living facility, and Alzheimer’s special care facility, as well as

community-based services such as adult day care and services provided in the home, including nursing care and help with personal care [412]. The 2016 Alzheimer’s Association Family Impact of Alzheimer’s Survey reported in 2016 Alzheimer’s Disease Facts and Figures found that among the more than 3500 respondents, 28 percent believed that Medicare covered the cost of nursing home care for peo- ple with Alzheimer’s and 37 percent did not know whether it covered the cost of nursing home care [265]. While Medi- care covers care in a long-term care hospital, skilled nursing care in a skilled nursing facility and hospice care, it does not cover long-term care in a nursing home [413].

Industryreportsestimatethatapproximately7.3to7.5million Americans have long-term care insurance [414,415]. Enrollment in private long-term care insurance is more common for older adults with higher-than-average incomes. While only 8.8 percent of adults age 55 and older had long-term care insurance in 2008, 19 percent of those with incomes greater than $100,000 had coverage [416]. Private health and long-term care insurance policies funded only about 8 percent of total long-term care spending in 2013, representing $24.8 billion of the $310 billion total in 2013 dollars [417]. The private long-term care insurance market has consolidated since 2010. Five major insurance carriers either exited the market or substantially increased premiums, making policies unaffordable for many individuals [418].

6.3.2.3. Medicaid costs Medicaid covers nursing home care and long-term care

services in the community for individuals who meet program requirements for level of care, income and assets. To receive coverage, beneficiaries must have low incomes. Most nursing home residents who qualify for Medicaid must spend all of their Social Security income and any other monthly income, except for a very small personal needs allowance, to pay for nursing home care. Medicaid only makes up the difference if the nursing home resident cannot pay the full cost of care or has a financially dependent spouse. There is a general lack of knowledge about Medicaid coverage and long-term care. In a survey about the financial impact of Alzheimer’s and other dementias on families, 36 percent of respondents mistakenly believed that Medicaid was long-term care insurance [265]. While Medicaid covers the cost of nursing home care, its coverage of many long- term care and support services, such as assisted living care, home-based skilled nursing care and help with personal care, varies by state.

Total Medicaid spending for people with Alzheimer’s or other dementias is projected to be $44 billion in 2017 (in 2017 dollars).A21 Estimated state-by-state Medicaid spending on people with Alzheimer’s or other dementias in 2017 (in 2017 dollars) is included in Table 14. Total per-person Medicaid payments for Medicare beneficiaries age 65 and older with Alzheimer’s or other dementias were 23 times as great as Medicaid payments for other Medicare beneficiaries [380]. Much of the difference in

Table 14

Total Medicaid costs for Americans age 65 and older living with

Alzheimer’s or other dementias by state

State

2017 (in millions

of dollars)

2025 (in millions

of dollars)

Percentage

increase

Alabama $797 $1092 37.0

Alaska 59 107 82.5

Arizona 332 530 59.7

Arkansas 335 440 31.2

California 3464 5085 46.8

Colorado 526 765 45.3

Connecticut 880 1151 30.8

Delaware 212 303 43.1

District of Columbia 115 131 13.7

Florida 2279 3347 46.9

Georgia 1038 1544 48.7

Hawaii 196 276 40.6

Idaho 129 190 47.8

Illinois 1565 2134 36.4

Indiana 913 1196 30.9

Iowa 598 768 28.4

Kansas 403 526 30.7

Kentucky 685 920 34.3

Louisiana 658 905 37.6

Maine 187 266 42.1

Maryland 1042 1488 42.8

Massachusetts 1550 1970 27.1

Michigan 1299 1685 29.7

Minnesota 781 1055 35.1

Mississippi 536 707 31.8

Missouri 843 1102 30.7

Montana 139 197 41.8

Nebraska 310 398 28.5

Nevada 158 269 70.6

New Hampshire 225 325 44.6

New Jersey 1887 2534 34.3

New Mexico 177 270 52.4

New York 4598 6128 33.3

North Carolina 1112 1580 42.1

North Dakota 166 209 25.7

Ohio 2242 2851 27.2

Oklahoma 440 592 34.6

Oregon 222 308 38.6

Pennsylvania 3236 3907 20.7

Rhode Island 416 548 31.5

South Carolina 544 793 45.8

South Dakota 157 205 30.6

Tennessee 939 1335 42.1

Texas 2493 3832 53.7

Utah 152 228 50.5

Vermont 98 142 44.3

Virginia 826 1228 48.7

Washington 461 669 45.0

West Virginia 394 505 28.3

Wisconsin 687 897 30.6

Wyoming 71 108 52.1

U.S. Total $43,570 $59,739 37.1

NOTE. Created from data from the Lewin Model. A21

All cost figures are reported in 2017 dollars. State totals may not add to

the U.S. total due to rounding.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373356

payments for beneficiaries with Alzheimer’s or other dementias and other beneficiaries is due to the costs associated with long-term care (nursing homes and other

residential care facilities, such as assisted living facilities) and the greater percentage of people with dementia who are eligible for Medicaid.

6.3.3. Use and costs of care at the end of life Hospice care provides medical care, pain management

and emotional and spiritual support for people who are dying, including people with Alzheimer’s or other demen- tias. Hospice care also provides emotional and spiritual sup- port and bereavement services for families of people who are dying. The main purpose of hospice is to allow individuals to die with dignity and without pain and other distressing symptoms that often accompany terminal illness. Individ- uals can receive hospice care in their homes, assisted living residences or nursing homes. Medicare is the primary source of payment for hospice care, but private insurance, Medicaid and other sources also pay for hospice care.

In 2014, 20 percent of Medicare beneficiaries admitted to hospice had a primary diagnosis of dementia, including Alzheimer’s dementia (Table 15) [419], compared with 17 percent in 2009 [420]. Dementia was the second most common primary diagnosis for Medicare beneficiaries admitted to hospice overall, with cancer being the most com- mon primary diagnosis. For all Medicare beneficiaries admitted to hospice, the average length of stay was 69 days in 2014, with 27 percent having a stay of seven or fewer days in hospice. While average length of stay for hos- pice beneficiaries by primary diagnosis was not publicly re- ported for 2014, the average length of stay was 106 days for hospice beneficiaries with a primary diagnosis of Alzheimer’s dementia and 92 days for hospice beneficiaries with non-Alzheimer’s dementia in 2009 [420]. The average per-person hospice payment for Medicare beneficiaries with Alzheimer’s dementia was $1966 compared with $149 for all other Medicare beneficiaries [380].

For Medicare beneficiaries with advanced dementia who receive skilled nursing facility care in the last 90 days of life, those who are enrolled in hospice are less likely to die in the hospital [421]. Additionally those enrolled in hospice care are less likely to be hospitalized in the last 30 days of life [422] and more likely to receive regular treat- ment for pain [423,424]. Nearly half of individuals with dementia die in hospice care [425]. Additionally, 19 percent of individuals with dementia receive hospice care in a given year, a higher percentage than for other chronic conditions [188]. Satisfaction with patient care is higher for families of individuals with dementia who are enrolled in hospice care than for those not enrolled in hospice care [426].

6.3.3.1. Feeding tube use and care transitions at the end of life

Individuals with frequent transitions between health care settings are more likely to have feeding tubes at the end of life, even though feeding tube placement has little or no benefit [384]. The odds of having a feeding tube inserted at the end of life vary across the country and are not

Table 15

Number of Medicare beneficiaries admitted to hospice and percentage with

dementia by state, 2014

State

Number of

beneficiaries

Percentage with a

primary diagnosis

of dementia

Alabama 28,051 21

Alaska 732 22

Arizona 34,540 20

Arkansas 14,679 20

California 120,194 22

Colorado 18,465 17

Connecticut 13,827 20

Delaware 5051 13

District of Columbia 1383 17

Florida 114,869 18

Georgia 42,327 22

Hawaii 4928 24

Idaho 7759 19

Illinois 47,766 20

Indiana 29,262 18

Iowa 17,735 16

Kansas 13,655 20

Kentucky 16,458 15

Louisiana 21,787 23

Maine 6442 20

Maryland 19,577 18

Massachusetts 26,544 25

Michigan 50,399 17

Minnesota 21,673 21

Mississippi 15,004 22

Missouri 31,250 18

Montana 4069 16

Nebraska 7975 23

Nevada 10,081 18

New Hampshire 5256 21

New Jersey 32,148 22

New Mexico 8976 19

New York 45,817 18

North Carolina 42,538 19

North Dakota 2337 20

Ohio 65,314 20

Oklahoma 19,950 20

Oregon 19,214 19

Pennsylvania 65,878 19

Rhode Island 5916 26

South Carolina 27,101 24

South Dakota 2878 15

Tennessee 28,025 20

Texas 101,161 23

Utah 11,014 18

Vermont 2270 16

Virginia 28,224 21

Washington 23,635 21

West Virginia 9171 18

Wisconsin 27,688 19

Wyoming 1121 9

U.S. Total 1,322,114 20

NOTE. Created from data from the U.S. Centers for Medicare &

Medicaid Services [419].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 357

explained by severity of illness, restrictions on the use of artificial hydration and nutrition, ethnicity or gender. Researchers found that feeding tube use was highest for people with dementia whose care was managed by a

subspecialist physician or both a subspecialist and a general practitioner. By contrast, feeding tube use was lower among people with dementia whose care was managed by a general practitioner [427,428]. With the expansion of Medicare- supported hospice care, the use of feeding tubes in the last 90 days of life has decreased for individuals with Alz- heimer’s or other dementias [429]. Finally, with the increased focus on the lack of evidence supporting feeding tube use for people with advanced dementia, the proportion of nursing home residents receiving a feeding tube in the prior 12 months has decreased from nearly 12 percent in 2000 to less than 6 percent in 2014 [428].

Studies have demonstrated a decrease in the proportion of individuals with Alzheimer’s dementia who die in an acute care hospital, with end-of-life care shifting to home and nursing homes [425]. Additionally, more than twice as many individuals with the disease were receiving hospice care at the time of death in 2009 than in 2000 (48 percent in 2009 versus 20 percent in 2000). Similarly, expansion of hospice care is also associated with fewer individuals with dementia having more than two hospitalizations for any reason or more than one hospitalization for pneumonia, urinary tract infection,dehydrationor sepsisin the last90daysoflife[429].

6.4. Use and costs of health and long-term care services by race/ethnicity

Among Medicare beneficiaries with Alzheimer’s or other dementias, African-Americans had the highest Medicare payments per person, while whites had the lowest spending ($26,686 versus $19,734) (Table 16). The largest difference in spending is for hospital care, for which Medicare spends 1.7 times more for African-Americans than for whites ($8690 versus $5163) [188].

In a study of Medicaid beneficiaries with a diagnosis of Alzheimer’s dementia that included both Medicaid and Medicare claims data, researchers found significant differences in the costs of care by race/ethnicity [430]. These results demonstrated that African-Americans had signifi- cantly higher costs of care than whites or Hispanics, primarily due to more inpatient care and more comorbidities. These differences may be attributable to later-stage diagnosis, which may lead to higher levels of disability while receiving care; delays in accessing timely primary care; lack of care coordination; and duplication of services across providers. However, more research is needed to un- derstand the reasons for this health care disparity.

6.5. Avoidable use of health care and long-term care services

6.5.1. Preventable hospitalizations Preventable hospitalizations are one common measure

of health care quality. Preventable hospitalizations are hos- pitalizations for conditions that could have been avoided with better access to or quality of preventive and primary

Table 16

Average annual per-person payments by type of service and race/ethnicity for Medicare beneficiaries age 65 and older, with and without Alzheimer’s or other

dementias, 2014, in 2016 dollars

Total Medicare

payments per person Hospital care Physician care

Skilled nursing

facility care

Home

health care Hospice care

White $19,734 $5163 $1611 $3367 $1695 $3128

African-American 26,686 8690 2185 4174 2072 2316

Hispanic 21,151 6986 1900 3209 1787 1724

Other 25,675 7858 2137 3362 3671 2549

NOTE. Created from unpublished data from the National 5% Sample Medicare Fee-for-Service Beneficiaries for 2014 [188].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373358

care. Based on data from the 2006 to 2008 Health and Retirement Study and from Medicare, preventable hospital- izations represented 25 percent of the total hospitalizations for individuals with Alzheimer’s or other dementias [431]. The proportion was substantially higher, however, for African-Americans, Hispanics and individuals with low incomes. Hispanic older adults had the highest proportion of preventable hospitalizations (34 percent). Based on data from the 1998 to 2008 Health and Retirement Study and from Medicare, after controlling for demographic characteristics, clinical characteristics and health risk factors, individuals with dementia had a 1.3 times greater risk and individuals with depression and dementia had a 1.7 times greater risk of having a preventable hospitaliza- tion than those without dementia, cognitive impairment without dementia or depression [432]. Healthy People 2020, the U.S. Department of Health and Human Services’ initiative to achieve 10-year goals for health promotion and disease prevention, has set a target to reduce preventable hospitalizations for people with Alzheimer’s or other de- mentias by 10 percent by 2020 [431].

Medicare beneficiaries who have Alzheimer’s or other dementias and a serious coexisting medical condition (for example, congestive heart failure) are more likely to be hospitalized than people with the same coexisting medical condition but without dementia (Figure 13) [188]. One

Fig. 13. Hospital stays per 1000 Medicare beneficiaries age 65 and older with spe

dementias, 2014. Created from unpublished data from the National 5% Sample M

research team found that individuals hospitalized with heart failure are more likely to be readmitted or die after hospital discharge if they also have cognitive impairment [433]. Another research team found that Medicare beneficiaries with Alzheimer’s or other dementias have more potentially avoidable hospitalizations for diabetes complications and hypertension, meaning that the hospitalizations could possibly be prevented through proactive care management in the outpatient setting [434].

Differences in health care use between individuals with and without dementia are most prominent for those residing in the community. Based on data from the Health and Retirement Study, community-residing individuals with dementia were more likely to have a potentially preventable hospitalization, an emergency department visit that was poten- tially avoidable, and/or an emergency department visit that re- sulted in a hospitalization [435]. For individuals residing in a nursing home, there were no differences in the likelihood of being hospitalized or having an emergency department visit.

6.5.2. Initiatives to reduce avoidable health care and nursing home use

Recent research has demonstrated that two types of programs have potential for reducing avoidable health care and nursing home use, with one type of program focusing on the caregiver and the other focusing on the care delivery

cified coexisting medical conditions, with and without Alzheimer’s or other

edicare Fee-for-Service Beneficiaries for 2014 [188].

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 359

team. The Caregiving section describes caregiver support programs that have promise for reducing unnecessary emergency department visits and hospitalizations and reducing transitions to residential care for individuals with Alzheimer’s or other dementias. Additionally, collaborative care models—models that include not only geriatricians, but also social workers, nurses and medical assistants—can improve care coordination, thereby reducing health care costs associated with hospitalizations, emergency depart- ment visits and other outpatient visits [373]. For example, an interprofessional memory care clinic was shown to reduce per-person health care costs by $3474 in 2012 dollars ($3871 in 2016 dollars) over a year for individuals with memory problems compared with others whose care was overseen by a primary care provider only [373]. More than half of the cost savings was attributed to lower inpatient hospital costs. The program was relatively low cost per person, with an average annual cost of $618 ($689 in 2016 dollars) — a nearly 6-to-1 return on investment.

Another group of researchers found that individuals with dementia whose care was concentrated within a smaller number of clinicians had fewer hospitalizations and emer- gency department visits and lower health care spending overall, compared with individuals whose care was more dispersed across a larger number of clinicians [436]. More research is needed to understand whether continuity of care is a strategy for decreasing unnecessary health care use for people with Alzheimer’s or other dementias.

6.6. Projections for the future

Total annual payments for health care, long-term care and hospice care for people with Alzheimer’s or other dementias are projected to increase from $259 billion in 2017 to more than $1.1 trillion in 2050 (in 2017 dollars). This dramatic rise includes more than four-fold increases both in govern- ment spending under Medicare and Medicaid and in out- of-pocket spending.A21

Acknowledgments

The Alzheimer’s Association acknowledges the contri- butions of Joseph Gaugler, Ph.D., Bryan James, Ph.D., Tricia Johnson, Ph.D., and Jennifer Weuve, M.P.H., Sc.D., in the preparation of 2017 Alzheimer’s Disease Facts and Figures.

References

[1] Wilson RS, Segawa E, Boyle PA, Anagnos SE, Hizel LP, Bennett DA.

The natural history of cognitive decline in Alzheimer’s disease. Psy-

chol Aging 2012;27:1008–17.

[2] Barker WW, Luis CA, Kashuba A, Luis M, Harwood DG,

Loewenstein D, et al. Relative frequencies of Alzheimer’s disease,

Lewy body, vascular and frontotemporal dementia, and hippocampal

sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc

Disord 2002;16:203–12.

[3] Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and de-

mentia: How to move forward? Neurology 2009;72:368–74.

[4] Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pa-

thologies account for most dementia cases in community-dwelling

older persons. Neurology 2007;69:2197–204.

[5] Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA. The neuro-

pathology of probable Alzheimer disease and mild cognitive impair-

ment. Ann Neurol 2009;66:200–8.

[6] Jellinger KA, Attems J. Neuropathological evaluation of mixed de-

mentia. J Neurol Sci 2007;257:80–7.

[7] Jellinger KA. The enigma of mixed dementia. Alzheimers Dement

2007;3:40–53.

[8] Clarfield AM. The decreasing prevalence of reversible dementias: An

updated meta-analysis. Arch Intern Med 2003;163:2219–29.

[9] Katzman R. The prevalence and malignancy of Alzheimer disease: A

major killer. Arch Neurol 1976;33:217–8.

[10] Fernando MS, Ince PG. MRC Cognitive Function and Ageing Neuro-

pathology Study Group. Vascular pathologies and cognition in a

population-basedcohortofelderlypeople.JNeurolSci2004;226:13–7.

[11] Verrees M, Selman WR. Management of normal pressure hydroceph-

alus. Am Fam Physician 2004;70:1071–8.

[12] Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA,

Salvado O, et al. Amyloid ß deposition, neurodegeneration, and

cognitive decline in sporadic Alzheimer’s disease: A prospective

cohort study. Lancet Neurol 2013;12:357–67.

[13] Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardos C, Jime-

nez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in

young adults at genetic risk for autosomal dominant Alzheimer’s dis-

ease in the presenilin 1 E280A kindred: A case-control study. Lancet

Neurol 2012;11:1048–56.

[14] Jack CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML,

Knopman DS, et al. Serial PiB and MRI in normal, mild cognitive

impairment and Alzheimer’s disease: Implications for sequence of

pathological events in Alzheimer’s disease. Brain 2009;132:1355–65.

[15] Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC,

et al. Clinical and biomarker changes in dominantly inherited Alz-

heimer’s disease. N Engl J Med 2012;367:795–804.

[16] Roberts R, Knopman DS. Classification and epidemiology of MCI.

Clin Geriatr Med 2013;29:753–72.

[17] Kantarci K, Weigand SD, Przybelski SA, Shiung MM, Whitwell JL,

Negash S, et al. Risk of dementia in MCI: Combined effect of cerebrovas-

cular disease, volumetric MRI, and 1H MRS. Neurology 2009;

72:1519–25.

[18] Mitchell AJ, Shiri-Feshki M. Rate of progression of mild cognitive

impairment to dementia: Meta-analysis of 41 robust inception cohort

studies. Acta Psychiatr Scand 2009;119:252–65.

[19] Ward A, Tardiff S, Dye C, Arrighi HM. Rate of conversion from pro-

dromal Alzheimer’s disease to Alzheimer’s dementia: A systematic re-

view of the literature. Dement Geriatr Cogn Dis Extra 2013;3:320–32.

[20] Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM,

et al. Toward defining the preclinical stages of Alzheimer’s disease:

Recommendations from the National Institute on Aging-Alzheimer’s

Association workgroups on diagnostic guidelines for Alzheimer’s

disease. Alzheimers Dement 2011;7:280–92.

[21] Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox N,

et al. The diagnosis of mild cognitive impairment due to Alzheimer’s

disease: Recommendations from the National Institute on Aging-

Alzheimer’s Association workgroups on diagnostic guidelines for

Alzheimer’s disease. Alzheimers Dement 2011;7:270–9.

[22] McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR,

Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s dis-

ease: Recommendations from the National Institute on Aging-Alz-

heimer’s Association workgroups on diagnostic guidelines for

Alzheimer’s disease. Alzheimers Dement 2011;7:263–9.

[23] Jack CR, Albert MS, Knopman DS, McKhann GM, Sperling RA,

Carrillo MC, et al. Introduction to the recommendations from the Na-

tional Institute on Aging-Alzheimer’s Association workgroups on

diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement

2011;7:257–62.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373360

[24] Bekris LM, Yu CE, Bird TD, Tsuang DW. Genetics of Alzheimer dis-

ease. J Geriatr Psychiatry Neurol 2010;23:213–27.

[25] Goldman JS, Hahn SE, Bird T. Genetic counseling and testing for

Alzheimer disease: Joint practice guidelines of the American College

of Medical Genetics and the National Society of Genetic Counselors.

Genet Med 2011;13:597–605.

[26] National Down Syndrome Society. Available at: http://www.ndss.org/

Down-Syndrome/What-Is-Down-Syndrome/. Accessed November 24,

2016.

[27] Lott IT, Dierssen M. Cognitive deficits and associated neurological

complications in individuals with Down’s syndrome. Lancet Neurol

2010;9:623–33.

[28] National Down Syndrome Society. An Introduction to Alzheimer’s, http://

www.ndss.org/Resources/Aging-Matters/Alzheimers-Disease/An-Intr

oduction-to-Alzheimers-Disease/. Accessed October 20, 2016.

[29] National Institutes of Health. National institute on Aging. Alzheimer’s

Dis People Down Syndr Fact Sheet. Available at: https://www.nia.nih.

gov/alzheimers/publication/alzheimers-disease-people-down-syndrome.

Accessed October 20, 2016.

[30] Hebert LE, Bienias JL, Aggarwal NT, Wilson RS, Bennett DA,

Shah RC, et al. Change in risk of Alzheimer disease over time.

Neurology 2010;75:786–91.

[31] Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the

United States (2010-2050) estimated using the 2010 Census.

Neurology 2013;80:1778–83.

[32] Green RC, Cupples LA, Go R, Benke KS, Edeki T, Griffith PA, et al.

Risk of dementia among white and African American relatives of pa-

tients with Alzheimer disease. JAMA 2002;287:329–36.

[33] Fratiglioni L, Ahlbom A, Viitanen M, Winblad B. Risk factors for

late-onset Alzheimer’s disease: A population-based, case-control

study. Ann Neurol 1993;33:258–66.

[34] Mayeux R, Sano M, Chen J, Tatemichi T, Stern Y. Risk of dementia in

first-degree relatives of patients with Alzheimer’s disease and related

disorders. Arch Neurol 1991;48:269–73.

[35] Lautenschlager NT, Cupples LA, Rao VS, Auerbach SA, Becker R,

Burke J, et al. Risk of dementia among relatives of Alzheimer’s dis-

ease patients in the MIRAGE Study: What is in store for the oldest

old? Neurology 1996;46:641–50.

[36] Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH,

Pericak-Vance MA, Joo SH, et al. Association of apolipoprotein E

allele epsilon 4 with late-onset familial and sporadic Alzheimer’s dis-

ease. Neurology 1993;43:1467–72.

[37] Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA,

Mayeux R, et al. Effects of age, sex, and ethnicity on the association

between apolipoprotein E genotype and Alzheimer disease: A meta-

analysis. JAMA 1997;278:1349–56.

[38] Loy CT, Schofield PR, Turner AM, Kwok JBJ. Genetics of dementia.

Lancet 2014;383:828–40.

[39] Mahley RW, Rall SC Jr. Apolipoprotein E: Far more than a lipid

transport protein. Annu Rev Genomics Hum Genet 2000;1:507–37.

[40] Raber J, Huang Y, Ashford JW. ApoE genotype accounts for thevast ma-

jority of AD risk and AD pathology. Neurobiol Aging 2004;25:641–50.

[41] Holtzman DM, Herz J, Bu G. Apolipoprotein E and apolipoprotein E

receptors: Normal biology and roles in Alzheimer disease. Cold

Spring Harb Perspect Med 2012;2:a006312.

[42] Alzheimer’s Drug Discovery Foundation. What APOE Means for Your

Health. Available at: http://www.alzdiscovery.org/cognitive-vitality/

what-apoe-means-for-your-health. Accessed November 24, 2016.

[43] Spinney L. Alzheimer’s disease: The forgetting gene. Nature 2014;

510:26–8.

[44] Ward A, Crean S, Mercaldi CJ, Collins JM, Boyd D, Cook MN, et al.

Prevalence of apolipoprotein e4 genotype and homozygotes (APOE

e4/4) among patients diagnosed with Alzheimer’s disease: A system-

atic review and meta-analysis. Neuroepidemiology 2012;38:1–17.

[45] Mayeux R, Saunders AM, Shea S, Mirra S, Evans D, Roses AD, et al.

Utility of the apolipoprotein E genotype in the diagnosis of Alz-

heimer’s disease. N Engl J Med 1998;338:506–11.

[46] Chouraki V, Seshadri S. Genetics of Alzheimer’s disease. Adv Genet

2014;87:245–94.

[47] Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H.

Summary of the evidence on modifiable risk factors for cognitive

decline and dementia: A population-based perspective. Alzheimers

Dement 2015;11:718–26.

[48] Institute of Medicine. Cognitive Aging: Progress in Understanding

and Opportunity for Action. Washington, D.C.: The National Acad-

emies Press; 2015.

[49] The Brain: Our Sense of Self. https://science.education.nih.gov/

supplements/nih4/self/activities/activities_toc.html. Accessed Nov-

ember 24, 2016.

[50] Anstey KJ, von Sanden C, Salim A, O’Kearney R. Smoking as a risk

factor for dementia and cognitive decline: A meta-analysis of pro-

spective studies. Am J Epidemiol 2007;166:367–78.

[51] Rusanen M, Kivipelto M, Quesenberry CP, Zhou J, Whitmer RA.

Heavy smoking in midlife and long-term risk of Alzheimer disease

and vascular dementia. Arch Intern Med 2011;171:333–9.

[52] Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB,

Wang Y. Epidemiologic studies of modifiable factors associated with

cognition and dementia: Systematic review and meta-analysis. BMC

Public Health 2014;14:643.

[53] R€onnemaa E, Zethelius B, Lannfelt L, Kilander L. Vascular risk fac-

tors and dementia: 40-year follow-up of a population-based cohort.

Dement Geriatr Cogn Disord 2011;31:460–6.

[54] Loef M, Walach H. Midlife obesity and dementia: Meta-analysis and

adjusted forecast of dementia prevalence in the United States and

China. Obesity (Silver Spring) 2013;21:E51–5.

[55] Anstey KJ, Cherbuin N, Budge M, Young J. Body mass index in

midlife and late-life as a risk factor for dementia: A meta-analysis

of prospective studies. Obes Rev 2011;12:e426–37.

[56] Wu W, Brickman AM, Luchsinger J, Ferrazzano P, Pichiule P,

Yoshita M, et al. The brain in the age of old: The hippocampal forma-

tion is targeted differentially by diseases of late life. Ann Neurol

2008;64:698–706.

[57] Gudala K, Bansal D, Schifano F, Bhansali A. Diabetes mellitus and

risk of dementia: A meta-analysis of prospective observational

studies. Diabetes Investig 2013;4:640–50.

[58] Vagelatos NT, Eslick GD. Type 2 diabetes as a risk factor for Alz-

heimer’s disease: The confounders, interactions, and neuropathology

associated with this relationship. Epidemiol Rev 2013;35:152–60.

[59] Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease.

Nat Rev Neurol 2011;7:137–52.

[60] Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, et al.

Glucose levels and risk of dementia. N Engl J Med 2013;369:540–8.

[61] Sajeev G, Weuve J, McQueen MB, Blacker D. Diabetes. The AlzRisk

Database. Alzheimer Research Forum. Available at: http://www.

alzrisk.org. Accessed November 30, 2016.

[62] Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR,

et al. Midlife blood pressure and dementia: The Honolulu-Asia Aging

Study. Neurobiol Aging 2000;21:49–55.

[63] Ninomiya T, Ohara T, Hirakawa Y, Yoshida D, Doi Y, Hata J, et al.

Midlife and late-life blood pressure and dementia in Japanese elderly:

The Hisayama Study. Hypertension 2011;58:22–8.

[64] Debette S, Seshadri S, Beiser A, Au R, Himali JJ, Palumbo C, et al.

Midlife vascular risk factor exposure accelerates structural brain ag-

ing and cognitive decline. Neurology 2011;77:461–8.

[65] Solomon A, Kivipelto M, Wolozin B, Zhou J, Whitmer RA.

Midlife serum cholesterol and increased risk of Alzheimer’s and

vascular dementia three decades later. Dement Geriatr Disord

2009;28:75–80.

[66] Meng XF, Yu JT, Wang HF, Tan MS, Wang C, Tan CC, et al. Midlife

vascular risk factors and the risk of Alzheimer’s disease: A systematic

review and meta-analysis. J Alzheimers Dis 2014;42:1295–310.

[67] Willis BL, Gao A, Leonard D, DeFina LF, Berry JD. Midlife fitness

and the development of chronic conditions in later life. Arch Intern

Med 2012;172:1333–40.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 361

[68] Harrington M, Weuve J, Jackson JW, Blacker D. Physical Activity.

The AlzRisk Database. Alzheimer Research Forum. Available at:

http://www.alzrisk.org. Accessed November 30, 2016.

[69] Tan ZS, Spartano NL, Beiser AS, DeCarli C, Auerbach SH,

Vasan RS, et al. Physical activity, brain volume, and dementia risk:

The Framingham Study. J Gerontol A Biol Sci Med Sci

2016;doi:10.1093/gerona/glw130 [epub ahead of print].

Accessed November 30, 2016.

[70] Willey JZ, Gardener H, Caunca MR, Moon YP, Dong C, Cheung YK,

et al. Leisure-time physical activity associates with cognitive decline:

The Northern Manhattan Study. Neurology 2016;86:1897–903.

[71] Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C,

Dartigues JF, et al. Dietary patterns and risk of dementia: The

Three-City Cohort Study. Neurology 2007;69:1921–30.

[72] Hardman RJ, Kennedy G, Macpherson H, Scholey AB, Pipingas A.

Adherence to a Mediterranean-style diet and effects on cognition in

adults: A qualitative evaluation and systematic review of longitudinal

and prospective trials. Front Nutr 2016;3:22.

[73] Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA,

Ukoumunne OC, et al. Mediterranean diet, cognitive function, and

dementia: A systematic review. Epidemiology 2013;24:479–89.

[74] Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL,

Bennett DA, et al. MIND diet slows cognitive decline with aging.

Alzheimers Dement 2015;11:1015–22.

[75] Loef M, Walach H. Fruit, vegetables and prevention of cognitive

decline or dementia: A systematic review of cohort studies. J Nutr

Health Aging 2012;16:626–30.

[76] Ngandu T, Lehtisalo J, Solomon A, Lev€alahti E, Ahtiluoto S,

Antikainen R, et al. A 2-year multidomain intervention of diet, exer-

cise, cognitive training, and vascular risk monitoring versus control to

prevent cognitive decline in at-risk elderly people (FINGER): A rand-

omised controlled trial. Lancet 2015;385:2255–63.

[77] Fitzpatrick AL, Kuller LH, Ives DG, Lopez OL, Jagust W,

Breitner JC, et al. Incidence and prevalence of dementia in the Car-

diovascular Health Study. J Am Geriatr Soc 2004;52:195–204.

[78] Kukull WA, Higdon R, Bowen JD, McCormick WC, Teri L,

Schellenberg GD, et al. Dementia and Alzheimer disease incidence:

A prospective cohort study. Arch Neurol 2002;59:1737–46.

[79] Evans DA, Bennett DA, Wilson RS, Bienias JL, Morris MC,

Scherr PA, et al. Incidence of Alzheimer disease in a biracial urban

community: Relation to apolipoprotein E allele status. Arch Neurol

2003;60:185–9.

[80] Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet

Neurol 2012;11:1006–12.

[81] Sando SB, Melquist S, Cannon A, Hutton M, Sletvold O, Saltvedt I,

et al. Risk-reducing effect of education in Alzheimer’s disease. Int J

Geriatr Psychiatry 2008;23:1156–62.

[82] Roe CM, Xiong C, Miller JP, Morris JC. Education and Alzheimer

disease without dementia: Support for the cognitive reserve hypoth-

esis. Neurology 2007;68:223–8.

[83] Stern Y. Cognitive reserve and Alzheimer disease. Alzheimer Dis As-

soc Disord 2006;20:112–7.

[84] Grzywacz JG, Segel-Karpas D, Lachman ME. Workplace exposures

and cognitive function during adulthood: Evidence from National

Survey of Midlife Development and the O*NET. J Occup Environ

Med 2016;58:535–41.

[85] Pool LR, Weuve J, Wilson RS, Buotmann U, Evans DA, Mendes de

Leon CF. Occupational cognitive requirements and late-life cognitive

aging. Neurology 2016;86:1386–92.

[86] Then FS, Luck T, Luppa M, Arelin K, Schroeter ML, Engel C, et al.

Association between mental demands at work and cognitive func-

tioning in the general population: Results of the health study of the

Leipzig Research Center for Civilization Diseases. J Occup Med Tox-

icol 2014;9:23.

[87] Fisher GG, Stachowski A, Infurna FJ, Faul JD, Grosch J, Tetrick LE.

Mental work demands, retirement, and longitudinal trajectories of

cognitive functioning. J Occup Health Psychol 2014;19:231–42.

[88] McDowell I, Xi G, Lindsay J, Tierney M. Mapping the connections

between education and dementia. J Clin Exp Neuropsychol 2007;

29:127–41.

[89] Harris CD, Watson KB, Carlson SA, Fulton JE, Dorn JM, Elam-

Evans L. Adult Participation in aerobic and muscle-strengthening

physical activities — United States, 2011. Morb Mortal Wkly Rep

2013;62:326–30.

[90] Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and

trends in diabetes among adults in the United States, 1988-2012.

JAMA 2015;314:1021–9.

[91] Sims M, Diez Roux AV, Boykin S, Sarpong D, Gebreab SY,

Wyatt SB, et al. The socioeconomic gradient of diabetes prevalence,

awareness, treatment, and control among African Americans in the

Jackson Heart Study. Ann Epidemiol 2011;21:892–8.

[92] Lee TC, Glynn RJ, Pe~na JM, Paynter NP, Conen D, Ridker PM, et al. Socioeconomic status and incident type 2 diabetes mellitus: Data

from the Women’s Health Study. PLoS One 2011;6:e27670.

[93] Steptoe A, Marmot M. Socioeconomic status and coronary heart dis-

ease: a psychobiological perspective. In: White LJ, ed. Aging,

Health, and Public Policy. New York: Population Council; 2005.

[94] Wang H-X, Xu W, Pei J-J. Leisure activities, cognition and dementia.

Biochim Biophys Acta 2012;1822:482–91.

[95] Wang H-X, Karp A, Winblad B, Fratiglioni L. Late-life engagement

in social and leisure activities is associated with a decreased risk of

dementia: A longitudinal study from the Kungsholmen Project. Am

J Epidemiol 2002;155:1081–7.

[96] Saczynski JS, Pfeifer LA, Masaki K, Korf ES, Laurin D, White L,

et al. The effect of social engagement on incident dementia:

The Honolulu-Asia Aging Study. Am J Epidemiol 2006;

163:433–40.

[97] Karp A, Paillard-Borg S, Wang H-X, Silverstein M, Winblad B,

Fratiglioni L. Mental, physical and social components in leisure ac-

tivities equally contribute to decrease dementia risk. Dement Geriatr

Cogn Disord 2005;21:65–73.

[98] Di Marco LY, Marzo A, Mu~noz-Ruiz M, Ikram MA, Kivipelto M,

Ruefenacht D, et al. Modifiable lifestyle factors in dementia: A sys-

tematic review of longitudinal observational cohort studies. J Alz-

heimers Dis 2014;42:119–35.

[99] Krueger KR, Wilson RS, Kamenetsky JM, Barnes LL, Bienias JL,

Bennett DA. Social engagement and cognitive function in old age.

Exp Aging Res 2009;35:45–60.

[100] Yates LA, Ziser S, Spector A, Orrell M. Cognitive leisure activities

and future risk of cognitive impairment and dementia: Systematic re-

view and meta-analysis. Int Psychogeriatr 2016;9:1–16.

[101] Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M,

et al. Effects of cognitive training interventions with older adults:

A randomized controlled trial. JAMA 2002;288:2271–81.

[102] Hall CB, Lipton RB, Sliwinski M, Katz MJ, Derby CA, Verghese J.

Cognitive activities delay onset of memory decline in persons who

develop dementia. Neurology 2009;73:356–61.

[103] Sanjeev G, Weuve J, Jackson JW, VanderWeele TJ, Bennett DA,

Grodstein F, et al. Late-life cognitive activity and dementia. Epidemi-

ology 2016;27:732–42.

[104] WilsonRS,BennettDA,BieniasJL,AggarwalNT,MendesDeLeonCF,

Morris MC, et al. Cognitive activity and incident AD in a population-

based sample of older persons. Neurology 2002;59:1910–4.

[105] Centers for Disease Control and Prevention. Get the Stats on Trau-

matic Brain Injury in the United States. Available at: http://www.

cdc.gov/traumaticbraininjury/pdf/BlueBook_factsheet-a.pdf. Accessed

November 24, 2016.

[106] National Institutes of Health. Traumatic Brain Injury. Available

at: http://www.nlm.nih.gov/medlineplus/traumaticbraininjury.html.

Accessed November 24, 2016.

[107] Plassman BL, Havlik RJ, Steffens DC, Helms MJ, Newman TN,

Drosdick D, et al. Documented head injury in early adulthood and

risk of Alzheimer’s disease and other dementias. Neurology 2000;

55:1158–66.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373362

[108] Teasdale G, Jennett B. Assesment of coma and impaired conscious-

ness: A practical scale. Lancet 1974;2:81–4.

[109] Lye TC, Shores EA. Traumatic brain injury as a risk factor for Alz-

heimer’s disease: A review. Neuropsychol Rev 2000;10:115–29.

[110] Gardner R, Yaffe K. Traumatic brain injury may increase risk of

young onset dementia. Ann Neurol 2014;75:339–41.

[111] Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A. Head

injury as a risk factor for Alzheimer’s disease: The evidence 10 years

on; a partial replication. J Neurol Neurosurg Psychiatry 2003;74:857–62.

[112] Shively S, Scher AI, Perl DP, Diaz-Arrastia R. Dementia resulting

from traumatic brain injury: What is the pathology? Arch Neurol

2012;69:1245–51.

[113] Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of sin-

gle and repetitive TBI: Substrates of dementia? Nat Rev Neurol 2013;

9:211–21.

[114] Guskiewicz KM. Association between recurrent concussion and late-

life cognitive impairment in retired professional football players.

Neurosurgery 2005;57:719–26.

[115] Institute for Social Research. National Football League Player Care

Foundation Study of NFL Retired Players. Ann Arbor, Mich: Univer-

sity of Michigan; 2009.

[116] Groswasser Z, Reider-Groswasser II, Schwab K, Ommaya AK,

Pridgen A, Brown HR, et al. Quantitative imaging in late TBI. Part

II: Cognition and work after closed and penetrating head injury: A

report of the Vietnam Head Injury Study. Brain Inj 2002;16:681–90.

[117] Salazar AM, Warden DL, Schwab K, Spector J, Braverman S,

Walter J, et al. Cognitive rehabilitation for traumatic brain injury:

A randomized trial. Defense and Veterans Head Injury Program

(DVHIP) Study Group. JAMA 2000;283:3075–81.

[118] Lehman EJ, Hein MJ, Baron SL, Gersic CM. Neurodegenerative

causes of death among retired National Football League players.

Neurology 2012;79:1970–4.

[119] Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL,

Wecht CH. Chronic traumatic encephalopathy in a National Football

League player. Neurosurgery 2005;57:128–34.

[120] McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE,

Daneshvar DH, et al. The spectrum of disease in chronic traumatic

encephalopathy. Brain 2013;136:43–64.

[121] Monti JM, Voss MW, Pence A, McAuley E, Kramer AF, Cohen NJ.

History of mild traumatic brain injury is associated with deficits in

relational memory, reduced hippocampal volume, and less neural ac-

tivity later in life. Front Aging Neurosci 2013;5:41.

[122] Roberts GW, Allsop D, Bruton C. The occult aftermath of boxing. J

Neurol Neurosurg Psychiatry 1990;53:373–8.

[123] McKee AC, Stein TD, Kiernan PT, Alvarez VE. The neuropathology

of chronic traumatic encephalopathy. Brain Pathol 2015;25:350–64.

[124] Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-

development pipeline: Few candidates, frequent failures. Alzheimer

Res Ther 2014;6:37.

[125] Groot C, Hooghiemstra AM, Raijmakers PG, van Berckel BN,

Scheltens P, Scherder E, et al. The effect of physical activity on cogni-

tive function in patients with dementia: A meta-analysis of random-

ized control trials. Ageing Res Rev 2016;25:13–23.

[126] Farina N, Rusted J, Tabet N. The effect of exercise interventions on

cognitive outcome in Alzheimer’s disease: A systematic review. Int

Psychogeriatr 2014;26:9–18.

[127] Aguirre E, Woods RT, Spector A, Orrell M. Cogntive stiumulation for

dementia: A systematic review of the evidence of effectiveness from

randomised controlled trials. Ageing Res Rev 2013;12:253–62.

[128] Vickrey BG, Mittman BS, Connor KI, Pearson ML, Della Penna RD,

Ganiats TG, et al. The effect of a disease management intervention on

quality and outcomes of dementia care: A randomized, controlled

trial. Ann Intern Med 2006;145:713–26.

[129] Voisin T, Vellas B. Diagnosis and treatment of patients with severe

Alzheimer’s disease. Drugs Aging 2009;26:135–44.

[130] Grossberg GT, Christensen DD, Griffith PA, Kerwin DR, Hunt G,

Hall EJ. The art of sharing the diagnosis and management of Alz-

heimer’s disease with patients and caregivers: Recommendations of

an expert consensus panel. Prim Care Companion J Clin Psychiatry

2010;12. PCC.09cs00833.

[131] McKhann G, Drachman D, Folstein M, Katzman R, Price D,

Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of

the NINCDS-ADRDAWork Group under the auspices of Department

of Health and Human Services Task Force on Alzheimer’s Disease.

Neurology 1984;34:939–44.

[132] Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ,

Carrillo MC, et al. National Institute on Aging-Alzheimer’s Associ-

ation guidelines on neuropathologic assessment of Alzheimer’s dis-

ease. Alzheimers Dement 2012;8:1–13.

[133] McKhann GM, Albert MS, Sperling RA. Changing diagnostic con-

cepts of Alzheimer’s Disease. In: Hampel H, Carrillo MC, eds. Alz-

heimer’s Disease — Modernizing concept, biological diagnosis and

therapy. Basel, Switzerland: Karger; 2012. p. 115–21.

[134] Bloudek LM, Spackman ED, Blankenburg M, Sullivan SD. Review

and meta-analysis of biomarkers and diagnostic imaging in Alz-

heimer’s disease. J Alzheimers Dis 2011;26:627–45.

[135] He W, Goodkind D, Kowal P. U.S. Census Bureau, International Pop-

ulation Reports, P95/16–1, An Aging World: 2015, U.S. Government

Publishing Office, Washington, DC, 2016. Available at:http://www.

census.gov/content/dam/Census/library/publications/2016/demo/p95-

16-1.pdf. Accessed November 24, 2016.

[136] Administration on Aging, Administration for Community Living,

U.S. Department of Health and Human Services. A Profile Old Amer-

icans: 2015. Available at: http://www.aoa.acl.gov/aging_statistics/

profile/2015/docs/2015-Profile.pdf. Accessed November 24, 2016.

[137] Alzheimer’s Association. Early-Onset Dementia: A National Challenge,

a Future Crisis. Washington, D.C.: Alzheimer’s Association; 2006.

[138] Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR,

Ofstedal MB, et al. Prevalence of dementia in the United States:

The Aging, Demographics, and Memory Study. Neuroepidemiology

2007;29:125–32.

[139] Wilson RS, Weir DR, Leurgans SE, Evans DA, Hebert LE, Langa KM,

et al. Sources of variability in estimates of the prevalence of Alzheimer’s

disease in the United States. Alzheimers Dement 2011;7:74–9.

[140] Boustani M, Peterson B, Hanson L, Harris R, Lohr KN. Screening for

dementia in primary care: A summary of the evidence for the U.S.

Preventive Services Task Force. Ann Intern Med 2003;138:927–37.

[141] Bradford A, Kunik ME, Schultz P, Williams SP, Singh H. Missed and

delayed diagnosis of dementia in primary care: Prevalence and

contributing factors. Alzheimer Dis Assoc Disord 2009;23:306–14.

[142] Kotagal V, Langa KM, Plassman BL, Fisher GG, Giordani BJ,

Wallace RB, et al. Factors associated with cognitive evaluations in

the United States. Neurology 2015;84:64–71.

[143] Barrett AM, Orange W, Keller M, Damgaard P, Swerdlow RH. Short-

term effect of dementia disclosure: How patients and families

describe the diagnosis. J Am Geriatr Soc 2006;54:1968–70.

[144] Campbell P, Wright J, Oyebode J, Job D, Crome P, Bentham P, et al.

Determinants of burden in those who care for someone with demen-

tia. Int J Geriatr Psychiatry 2008;23:1078–85.

[145] ZaletaAK,CarpenterBD,PorenskyEK,XiongC,MorrisJC.Agreement

on diagnosis among patients, companions, and professionals after a de-

mentia evaluation. Alzheimer Dis Assoc Disord 2012;26:232–7.

[146] Amjad H, Roth DL, Samus QM, Yasar S, Wolff JL. Potentially unsafe

activities and living conditions of older adults with dementia. J Am

Geriatr Soc 2016;64:1223–32.

[147] Reisberg B, Gauthier S. Current evidence for subjective cognitive

impairment (SCI) as the pre-mild cognitive impairment (MCI) stage

of subsequently manifest Alzheimer’s disease. Int Psychogeriatr

2008;20:1–16.

[148] JessenF,WolfsgruberS,WieseB,BickelH,M€oschE,KaduszkiewiczH, etal.ADdementiariskinlateMCI,inearlyMCI,andinsubjectivemem-

ory impairment. Alzheimers Dement 2014;10:76–83.

[149] Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M,

Ch�etelat G, et al. A conceptual framework for research on subjective

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 363

cognitive decline in preclinical Alzheimer’s disease. Alzheimers De-

ment 2014;10:844–52.

[150] Buckley RF, Maruff P, Ames D, Bourgeat P, Martins RN, Masters CL,

et al. Subjective memory decline predicts greater rates of clinical pro-

gression in preclinical Alzheimer’s disease. Alzheimers Dement

2016;12:796–804.

[151] Gifford KA, Liu D, Lu Z, Tripodis Y, Cantwell NG, Palmisano J, et al.

The source of cognitive complaints predicts diagnostic conversion

differentially among nondemented older adults. Alzheimers Dement

2014;10:319–27.

[152] Kaup AR, Nettiksimmons J, LeBlanc ES, Yaffe K. Memory com-

plaints and risk of cognitive impairment after nearly 2 decades among

older women. Neurology 2015;85:1852–8.

[153] Reisberg B, Shulman MB, Torossian C, Leng L, Zhu W. Outcome

over seven years of healthy adults with and without subjective cogni-

tive impairment. Alzheimers Dement 2010;6:11–24.

[154] Fernandez-Blazquez MA, Avila-Villanueva M, Maestu F, Medina M.

Specific features of subjective cognitive decline predict faster conversion

to mild cognitive impairment. J Alzheimers Dis 2016;52:271–81.

[155] Wolfsgruber S, Kleineidam L, Wagner M, M€osch E, Bickel H,

Lϋhmann D, et al. Differential risk of incident Alzheimer’s disease dementia in stable versus unstable patterns of subjective cognitive

decline. J Alzheimers Dis 2016;54:1135–46.

[156] Unpublished data from the 2015 Behavioral Risk Factor Surveillance

System survey (www.cdc.gov/brfss). Data were analyzed and pro-

vided to the Alzheimer’s Association by the Healthy Aging Program,

Centers for Disease Control and Prevention (CDC).

[157] Seshadri S, Wolf PA, Beiser A, Au R, McNulty K, White R, et al.

Lifetime risk of dementia and Alzheimer’s disease. The impact of

mortality on risk estimates in the Framingham Study. Neurology

1997;49:1498–504.

[158] Mielke MM, Vemuri P, Rocca WA. Clinical epidemiology of Alz-

heimer’s disease: Assessing sex and gender differences. Clin Epide-

miol 2014;6:37–48.

[159] Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA. Is the risk

of developing Alzheimer’s disease greater for women than for men?

Am J Epidemiol 2001;153:132–6.

[160] Chene G, Beiser A, Au R, Preis SR, Wolf PA, Dufouil C, et al. Gender

and incidence of dementia in the Framingham Heart Study from mid-

adult life. Alzheimers Dement 2015;11:310–20.

[161] Tom SE, Hubbard RA, Crane PK, Haneuse SJ, Bowen J,

McCormick WC, et al. Characterization of dementia and Alzheimer’s

disease in an older population: Updated incidence and life expectancy

with and without dementia. Am J Public Health 2015;105:408–13.

[162] Carter CL, Resnick EM, Mallampalli M, Kalbarczyk A. Sex and

gender differences in Alzheimer’s disease: Recommendations for

future research. J Womens Health 2012;21:1018–23.

[163] Altmann A, Tian L, Henderson VW, Greicius MD. Alzheimer’s Disease

Neuroimaging Initiative Investigators. Sex modifies the APOE-related

risk of developing Alzheimer disease. Ann Neurol 2014;75:563–73.

[164] Ungar L, Altmann A, Greicius MD. Apolipoprotein E, gender, and

Alzheimer’s disease: An overlooked, but potent and promising inter-

action. Brain Imaging Behav 2014;8:262–73.

[165] Yaffe K, Haan M, Byers A, Tangen C, Kuller L. Estrogen use, APOE,

and cognitive decline: Evidence of gene-environment interaction.

Neurology 2000;54:1949–54.

[166] Kang JH, Grodstein F. Postmenopausal hormone therapy, timing of

initiation, APOE and cognitive decline. Neurobiol Aging 2012;

33:1129–37.

[167] Rocca WA, Mielke MM, Vemuri P, Miller VM. Sex and gender dif-

ferences in the causes of dementia: A narrative review. Maturitas

2014;79:196–201.

[168] Dilworth-Anderson P, Hendrie HC, Manly JJ, Khachaturian AS,

Fazio S. Diagnosis and assessment of Alzheimer’s disease in diverse

populations. Alzheimers Dement 2008;4:305–9.

[169] Manly JJ, Mayeux R. Ethnic differences in dementia and Alzheimer’s

disease. In: Anderson N, Bulatao R, Cohen B, eds. Critical perspec-

tives on racial and ethnic differentials in health in late life. Washing-

ton, D.C.: National Academies Press; 2004. p. 95–141.

[170] Demirovic J, Prineas R, Loewenstein D, Bean J, Duara R, Sevush S,

et al. Prevalence of dementia in three ethnic groups: The South Flor-

ida Program on Aging and Health. Ann Epidemiol 2003;13:472–8.

[171] Harwood DG, Ownby RL. Ethnicity and dementia. Curr Psych Rep

2000;2:40–5.

[172] Perkins P, Annegers JF, Doody RS, Cooke N, Aday L, Vernon SW.

Incidence and prevalence of dementia in a multiethnic cohort of

municipal retirees. Neurology 1997;49:44–50.

[173] Steenland K, Goldstein FC, Levey A, Wharton W. A meta-analysis of

Alzheimer’s disease incidence and prevalence comparing African-

Americans and caucasians. J Alzheimers Dis 2015;50:71–6.

[174] Potter GG, Plassman BL, Burke JR, Kabeto MU, Langa KM,

Llewellyn DJ, et al. Cognitive performance and informant reports

in the diagnosis of cognitive impairment and dementia in African

Americans and whites. Alzheimers Dement 2009;5:445–53.

[175] Gurland BJ, Wilder DE, Lantigua R, Stern Y, Chen J, Killeffer EH,

et al. Rates of dementia in three ethnoracial groups. Int J Geriatr Psy-

chiatry 1999;14:481–93.

[176] Haan MN, Mungas DM, Gonzalez HM, Ortiz TA, Acharya A,

Jagust WJ. Prevalence of dementia in older latinos: The influence

of type 2 diabetes mellitus, stroke and genetic factors. J Am Geriatr

Soc 2003;51:169–77.

[177] Samper-Ternent R, Kuo YF, Ray LA, Ottenbacher KJ, Markides KS,

Al Snih S. Prevalence of health conditions and predictors of mortality

in oldest old Mexican Americans and non-Hispanic whites. J Am

Med Dir Assn 2012;13:254–9.

[178] Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequal-

ities in dementia incidence between six racial and ethnic groups over

14 years. Alzheimers Dement 2016;12:216–24.

[179] Yaffe K, Falvey C, Harris TB, Newman A, Satterfield S, Koster A,

et al. Effect of socioeconomic disparities on incidence of dementia

among biracial older adults: Prospective study. BMJ 2013;347:f7051.

[180] Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang LS,

et al. Variants in the ATP-binding cassette transporter (ABCA7),

apolipoprotein E epsilon 4, and the risk of late-onset Alzheimer dis-

ease in African Americans. JAMA 2013;309:1483–92.

[181] Froehlich TE, Bogardus ST Jr, Inouye SK. Dementia and race: Are

there differences between African Americans and Caucasians? J

Am Geriatr Soc 2001;49:477–84.

[182] Chin AL, Negash S, Hamilton R. Diversity and disparity in dementia:

The impact of ethnoracial differences in Alzheimer disease. Alz-

heimer Dis Assoc Disord 2011;25:187–95.

[183] Lines LM, Sherif NA, Wiener JM. Racial and ethnic disparities

among individuals with Alzheimer’s disease in the United States: A

literature review. Research Triangle Park, NC: RTI Press; 2014.

[184] Glymour MM, Manly JJ. Lifecourse social conditions and racial

and ethnic patterns of cognitive aging. Neuropsychol Rev 2008;

18:223–54.

[185] Zhang Z, Hayward MD, Yu YL. Life Course Pathways to racial dis-

parities in cognitive impairment among older Americans. J Health

Soc Behav 2016;57:184–99.

[186] Clark PC, Kutner NG, Goldstein FC, Peterson-Hazen S, Garner V,

Zhang R, et al. Impediments to timely diagnosis of Alzheimer’s dis-

ease in African Americans. J Am Geriatr Soc 2005;53:2012–7.

[187] Fitten LJ, Ortiz F, Ponton M. Frequency of Alzheimer’s disease and

other dementias in a community outreach sample of Hispanics. J Am

Geriatr Soc 2001;49:1301–8.

[188] Unpublished tabulations based on data from the National 5% Sample

Medicare Fee-for-Service Beneficiaries for 2014. Prepared under

contract by Avalere Health, 2016.

[189] Weuve J, Hebert LE, Scherr PA, Evans DA. Prevalence of Alzheimer

disease in U.S. states. Epidemiology 2015;26:e4–6.

[190] Hebert LE, Beckett LA, Scherr PA, Evans DA. Annual incidence of

Alzheimer disease in the United States projected to the years 2000

through 2050. Alzheimer Dis Assoc Disord 2001;15:169–73.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373364

[191] Manton KC, Gu XL, Ukraintseva SV. Declining prevalence of de-

mentia in the U.S. elderly population. Adv Gerontol 2005;16:30–7.

[192] Langa KM, Larson EB, Karlawish JH, Cutler DM, Kabeto MU,

Kim SY, et al. Trends in the prevalence and mortality of cognitive

impairment in the United States: Is there evidence of a compression

of cognitive morbidity? Alzheimers Dement 2008;4:134–44.

[193] Schrijvers EM, Verhaaren BF, Koudstaal PJ, Hofman A, Ikram MA,

Breteler MM. Is dementia incidence declining? Trends in dementia inci-

dence since 1990 in the Rotterdam Study. Neurology 2012;78:1456–63.

[194] Qiu C, von Strauss E, Backman L, Winblad B, Fratiglioni L. Twenty-

year changes in dementia occurrence suggest decreasing incidence in

central Stockholm, Sweden. Neurology 2013;80:1888–94.

[195] Christensen K, Thinggaard M, Oksuzyan A, Steenstrup T, Andersen-

Ranberg K, Jeune B, et al. Physical and cognitive functioning of peo-

ple older than 90 years: A comparison of two Danish cohorts born 10

years apart. Lancet 2013;382:1507–13.

[196] Dodge HH, Zhu J, Lee CW, Chang CC, Ganguli M. Cohort effects in

age-associated cognitive trajectories. J Gerontol A Biol Sci Med Sci

2014;69:687–94.

[197] Satizabal CL, Beiser AS, Chouraki V, Chene G, Dufouil C,

Seshadri S. Incidence of dementia over three decades in the Framing-

ham Heart Study. N Engl J Med 2016;374:523–32.

[198] Doblhammer G, Fink A, Zylla S, Fritze T, Willekens F. Short-term

trends in German dementia prevalence, incidence, and mortality. Pre-

sentation Alzheimer’s Assoc Int Conf; 2014.

[199] Matthews FE, Arthur A, Barnes LE, Bond J, Jagger C, Robinson L,

et al. A two-decade comparison of prevalence of dementia in individ-

uals aged 65 years and older from three geographical areas of En-

gland: Results of the Cognitive Function and Ageing Study I and

II. Lancet 2013;382:1405–12.

[200] Rocca WA, Petersen RC, Knopman DS, Hebert LE, Evans DA,

Hall KS, et al. Trends in the incidence and prevalence of Alzheimer’s

disease, dementia, and cognitive impairment in the United States.

Alzheimers Dement 2011;7:80–93.

[201] Matthews FE, Stephan BC, Robinson L, Jagger C, Barnes LE, Arthur A,

et al. A two decade dementia incidence comparison from the Cognitive

Function and Ageing Studies I and II. Nat Commun 2016;7:11398.

[202] Langa KM, Larson EB, Crimmins EM, Faul JD, Levine DA,

Kabeto MU, et al. A Comparison of the prevalence of dementia in the

United States in 2000 and 2012. JAMA Intern Med 2017;177:51–8.

[203] Langa KM. Is the risk of Alzheimer’s disease and dementia

declining? Alzheimers Res Ther 2015;7:34.

[204] Larson EB, Yaffe K, Langa KM. New insights into the dementia

epidemic. N Engl J Med 2013;369:2275–7.

[205] Prince MJ, Wimo A, Guerchet M, Ali G-C, Wu Y-T, Prina M. World

Alzheimer Rep 2015: The Glob Impact Demen Anal Prevalence,

Incidence, Cost Trends; 2015.

[206] Ortman JM, Velkoff VA, Hogan H. An Aging Nation: The Older Pop-

ulation in the United States, Current Population Reports, P25–1140.

Washington, D.C.: U.S. Census Bureau. Available at: http://www.

census.gov/content/dam/Census/library/publications/2014/demo/p25-

1140.pdf; 2014. Accessed November 24, 2016.

[207] Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alz-

heimer’s disease in the U.S. population: Prevalence estimates using

the 2000 Census. Arch Neurol 2003;60:1119–22.

[208] Kochanek KD, Murphy SL, Xu JQ, Tejada-Vera B. Deaths: Final

Data for 2014. Natl Vital Stat Rep 2016;65:1–122.

[209] World Health Organization. International Statistical Classification of

Diseases and Related Health Problems. 10th revision. 2nd edition.

Geneva, Switzerland: WHO Press; 2004.

[210] Burns A, Jacoby R, Luthert P, Levy R. Cause of death in Alzheimer’s

disease. Age Ageing 1990;19:341–4.

[211] Brunnstrom HR, Englund EM. Cause of death in patients with de-

mentia disorders. Eur J Neurol 2009;16:488–92.

[212] Ives DG, Samuel P, Psaty BM, Kuller LH. Agreement between nosol-

ogist and Cardiovascular Health Study review of deaths: Implications

of coding differences. J Am Geriatr Soc 2009;57:133–9.

[213] Romero JP, Benito-Leon J, Mitchell AJ, Trincado R, Bermejo-

Pareja F. Under reporting of dementia deaths on death certificates us-

ing data from a population-based study (NEDICES). J Alzheimers

Dis 2014;39:741–8.

[214] Romero JP, Benito-Leon J, Louis ED, Bermejo-Pareja F. Under re-

porting of dementia deaths on death certificates: A systematic review

of population-based cohort studies. J Alzheimers Dis 2014;

41:213–21.

[215] Ganguli M, Rodriguez EG. Reporting of dementia on death certifi-

cates: A community study. J Am Geriatr Soc 1999;47:842–9.

[216] James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA.

Contribution of Alzheimer disease to mortality in the United States.

Neurology 2014;82:1045–50.

[217] Weuve J, Hebert LE, Scherr PA, Evans DA. Deaths in the United

States among persons with Alzheimer’s disease (2010-2050). Alz-

heimers Dement 2014;10:e40–6.

[218] Arrighi HM, Neumann PJ, Lieberburg IM, Townsend RJ. Lethality of

Alzheimer disease and its impact on nursing home placement. Alz-

heimer Dis Assoc Disord 2010;24:90–5.

[219] National Center for Health Statistics. Deaths: Final Data for 2000.

National Vital Statistics Reports. Hyattsville, Md: National Center

for Health Statistics; 2002.

[220] Tejada-Vera B. Mortality from Alzheimer’s disease in the United

States: Data for 2000 and 2010. National Center for Health Statistics

Data Brief, No. 116. Hyattsville, Md: National Center for Health Sta-

tistics; 2013.

[221] Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST. Alzheimer

disease and mortality: A 15-year epidemiological study. Arch Neurol

2005;62:779–84.

[222] Waring SC, Doody RS, Pavlik VN, Massman PJ, Chan W. Survival

among patients with dementia from a large multi-ethnic population.

Alzheimer Dis Assoc Disord 2005;19:178–83.

[223] Brookmeyer R, Corrada MM, Curriero FC, Kawas C. Survival

following a diagnosis of Alzheimer disease. Arch Neurol 2002;

59:1764–7.

[224] Larson EB, Shadlen MF, Wang L, McCormick WC, Bowen JD,

Teri L, et al. Survival after initial diagnosis of Alzheimer disease.

Ann Intern Med 2004;140:501–9.

[225] Helzner EP, Scarmeas N, Cosentino S, Tang MX, Schupf N, Stern Y.

Survival in Alzheimer disease: A multiethnic, population-based

study of incident cases. Neurology 2008;71:1489–95.

[226] Xie J, Brayne C, Matthews FE. Survival times in people with demen-

tia: Analysis from a population based cohort study with 14-year

follow-up. BMJ 2008;336:258–62.

[227] Brodaty H, Seeher K, Gibson L. Dementia time to death: A system-

atic literature review on survival time and years of life lost in people

with dementia. Int Psychogeriatr 2012;24:1034–45.

[228] Todd S, Barr S, Roberts M, Passmore AP. Survival in dementia and

predictors of mortality: A review. Int J Geriatr Psychiatry 2013;

28:1109–24.

[229] Mitchell SL, Teno JM, Miller SC, Mor V. A national study of the

location of death for older persons with dementia. J Am Geriatr

Soc 2005;53:299–305.

[230] U.S. Burden of Disease Collaborators. The state of U.S. health, 1990-

2010: Burden of diseases, injuries, and risk factors. JAMA 2013;

310:591–608.

[231] Gaugler JE, Kane RL, Kane RA. Family care for older adults with

disabilities: Toward more targeted and interpretable research. Int J

Aging Hum Dev 2002;54:205–31.

[232] Schulz R, Quittner AL. Caregiving through the life-span: Overview

and future directions. Health Psychol 1998;17:107–11.

[233] Friedman EM, Shih RA, Langa KM, Hurd MD. U.S. prevalence and

predictors of informal caregiving for dementia. Health Aff 2015;

34:1637–41.

[234] Wolff JL, Spillman BC, Freedman VA, Kasper JD. A national profile

of family and unpaid caregivers who assist older adults with health

care activities. JAMA Intern Med 2016;176:372–9.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 365

[235] Only Walmart: 2016 Annual Report. Available at: http://www.

corporatereport.com/walmart/2016/ar/_pdf/WMT_2016AR.pdf. Ac-

cessed January 12, 2017.

[236] McDonald’s Corporation Report 2015. Available at: http://corporate.

mcdonalds.com/content/dam/AboutMcDonalds/Investors%202/2015

%20Annual%20Report.pdf. Accessed November 24, 2016.

[237] Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary

costs of dementia in the United States. N Engl J Med 2013;368:1326–34.

[238] Kasper JD, Freedman VA, Spillman BC, Wolff JL. The dispropor-

tionate impact of dementia on family and unpaid caregiving to older

adults. Health Aff 2015;34:1642–9.

[239] Kasper JD, Freedman VA, Spillman BC. Disability and Care Needs of

Older Americans by Dementia Status: An Analysis of the 2011 Na-

tional Health and Aging Trends Study. U.S. Department of Health

and Human Services; 2014. Available at: http://aspe.hhs.gov/report/

disability-and-care-needs-older-americans-dementia-status-analysis-

2011-national-health-and-aging-trends-study. Accessed November

24, 2016.

[240] Bouldin ED, Andresen E. Caregiving Across the United States: Care-

givers of Persons with Alzheimer’s Disease or Dementia in 8 States

and the District of Columbia. Data 2009 2010 Behav Risk Factor Sur-

veill Syst. Available at: http://www.alz.org/documents_custom/public-

health/2009-2010-combined-caregiving.pdf. Accessed November

24, 2016.

[241] Langa KM, Plassman BL, Wallace RB, Herzog AR, Heeringa SG,

Ofstedal MB, et al. The Aging, Demographics, and Memory Study:

Study design and methods. Neuroepidemiology 2005;25:181–91.

[242] Fisher GG, Franks MM, Plassman BL, Brown SL, Potter GG,

Llewellyn D, et al. Caring for individuals with dementia and cogni-

tive impairment, not dementia: Findings from The Aging, Demo-

graphics, and Memory Study. J Am Geriatr Soc 2011;59:488–94.

[243] National Alliance for Caregiving and AARP. Caregiving in the U.S.:

Unpublished data analyzed under contract for the Alzheimer’s Asso-

ciation; 2016.

[244] National Alliance for Caregiving and United Hospital Fund. Young

Caregivers in the U.S.: Report of Findings; September 2005.

Available at: www.caregiving.org/data/youngcaregivers.pdf. Ac-

cessed December 14, 2016.

[245] National Alliance for Caregiving and AARP. Caregiving in the U.S.:

Unpublished data analyzed under contract for the Alzheimer’s Asso-

ciation; 2009.

[246] Alzheimer’s Association. 2014 Alzheimer’s Disease Facts and Fig-

ures. Spec Rep Women Alzheimer’s Dis. Available at: https://www.

alz.org/downloads/Facts_Figures_2014.pdf. Accessed November

24, 2016.

[247] Pinquart M, S€orensen. Gender differences in caregiver stressors, so-

cial resources, and health: An updated meta-analysis. J Gerontol B

Psychol Sci Soc Sci 2006;61:P33–45.

[248] National Alliance for Caregiving and AARP. Caregiving in the U.S.

(2015). Available at: http://www.caregiving.org/wp-content/uploads/

2015/05/2015_CaregivingintheUS_Final-Report-June-4_WEB.pdf. Ac-

cessed November 24, 2016.

[249] Spillman B, Wolff J, Freedman VA, Kasper JD. Informal Caregiving

for Older Americans: An Analysis of the 2011 National Health and

Aging Trends Study. Available at: https://aspe.hhs.gov/report/

informal-caregiving-older-americans-analysis-2011-national-study-

caregiving. Accessed January 12, 2017.

[250] Garity J. Caring for a family member with Alzheimer’s disease:

Coping with caregiver burden post-nursing home placement. J Ger-

ontol Nurs 2006;32:39–48.

[251] Port CL, Zimmerman S, Williams CS, Dobbs D, Preisser JS,

Williams SW. Families filling the gap: Comparing family involve-

ment for assisted living and nursing home residents with dementia.

Gerontologist 2005;45:87–95.

[252] Schulz R, Belle SH, Czaja SJ, McGinnis KA, Stevens A, Zhang S.

Long-term care placement of dementia patients and caregiver health

and well-being. JAMA 2004;292:961–7.

[253] Rattinger GB, Schwartz S, Mullins CD, Corcoran C, Zuckerman IH,

Sanders C, et al. Dementia severity and the longitudinal costs of

informal care in the Cache County population. Alzheimers Dement

2015;11:946–54.

[254] Rattinger GB, Fauth EB, Behrens S, Sanders C, Schwartz S,

Norton MC, et al. Closer caregiver and care-recipient relationships

predict lower informal costs of dementia care: The Cache County De-

mentia Progression Study. Alz Dement 2016;12:917–24.

[255] Ornstein K, Gaugler JE. The problem with “problem behaviors”: A

systematic review of the association between individual patient

behavioral and psychological symptoms and caregiver depression

and burden within the dementia patient-caregiver dyad. Int Psycho-

geriatr 2012;24:1536–52.

[256] Vaingankar JA, Chong SA, Abdin E, Picco L, Shafie S, Seow E, et al.

Psychiatric morbidity and its correlates among informal caregivers of

older adults. Compr Psychiatry 2016;68:178–85.

[257] Feast A, Moniz-Cook E, Stoner C, Charlesworth G, Orrell M. A sys-

tematic review of the relationship between behavioral and psycholog-

ical symptoms (BPSD) and caregiver well-being. Int Psychogeriatr

2016;28:1761–74.

[258] Kiecolt-Glaser JK, Glaser R, Gravenstein S, Malarkey WB,

Sheridan J. Chronic stress alters the immune response to influenza vi-

rus vaccine in older adults. Proc Natl Acad Sci 1996;93:3043–7.

[259] Schulz R, Beach SR. Caregiving as a risk factor for mortality: The

Caregiver Health Effects Study. JAMA 1999;282:2215–60.

[260] Vitaliano PP, Zhang J, Scanlan JM. Is caregiving hazardous to

one’s physical health? A meta-analysis. Psychol Bull 2003;

129:946–72.

[261] Liu W, Gallagher-Thompson D. Impact of dementia caregiving:

Risks, strains, and growth. In: Qualls SH, Zarit SH, eds. Aging families

andcaregiving.Hoboken,N.J.:JohnWiley&Sons,Inc;2009.p.85–112.

[262] Pinquart M, S€orensen S. Associations of stressors and uplifts of care-

giving with caregiver burden and depressive mood: A meta-analysis.

J Gerontol B Psychol Sci Soc Sci 2003;58:112–28.

[263] S€orensen S, Duberstein P, Gill D, Pinquart M. Dementia care: Mental

health effects, intervention strategies, and clinical implications. Lan-

cet Neurol 2006;5:961–73.

[264] Goren A, Montgomery W, Kahle-Wrobleski K, Nakamura T, Ueda K.

Impact of caring for persons with Alzheimer’s disease or dementia on

caregivers’ health outcomes: Findings from a community based sur-

vey in Japan. BMC Geriatr 2016;16:122.

[265] Alzheimer’s Association. Facts and Figures. Special Report; 2016.

[266] Zarit S. Positive aspects of caregiving: More than looking on the

bright side. Aging Ment Health 2012;16:673–4.

[267] Cheng ST, Mak EP, Lau RW, Ng NS, Lam LC. Voices of Alzheimer

caregivers on positive aspects of caregiving. Gerontologist 2016;

56:451–60.

[268] Monin JK, Schulz R, Feeney BC. Compassionate love in

individuals with Alzheimer’s disease and their spousal caregivers: As-

sociations with caregivers’ psychological health. Gerontologist 2015;

55:981–9.

[269] Roth DL, Dilworth-Anderson P, Huang J, Gross AL, Gitlin LN. Pos-

itive aspects of family caregiving for dementia: Differential item

functioning by race. J Gerontol B Psychol Sci Soc Sci 2015;

70:813–9.

[270] Schulz R, O’Brien AT, Bookwala J, Fleissner K. Psychiatric and

physical morbidity effects of dementia caregiving: Prevalence, corre-

lates, and causes. Gerontologist 1995;35:771–91.

[271] Baumgarten M, Battista RN, Infante-Rivard C, Hanley JA, Becker R,

Gauthier S. The psychological and physical health of family mem-

bers caring for an elderly person with dementia. J Clin Epidemiol

1992;45:61–70.

[272] Mausbach BT, Chattillion EA, Roepke SK, Patterson TL, Grant I. A

comparison of psychosocial outcomes in elderly Alzheimer care-

givers and noncaregivers. Am J Geriatr Psychiatry 2013;21:5–13.

[273] Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prev-

alence, severity, and comorbidity of 12-month DSM-IV disorders in

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373366

the National Comorbidity Survey Replication. Arch Gen Psychiatry

2005;62:617–27.

[274] Sallim AB, Sayampanathan AA, Cuttilan A, Chun-Man Ho R. Prev-

alence of mental health disorders among caregivers of patients with

Alzheimer disease. J Am Med Dir Assoc 2015;16:1034–41.

[275] Thunyadee C, Sitthimongkol Y, Sangon S, Chai-Aroon T,

Hegadoren KM. Predictors of depressive symptoms and physical

health in caregivers of individuals with schizophrenia. J Nurs Health

Sci 2015;17:412–9.

[276] Atteih S, Mellon L, Hall P, Brewer L, Horgan F, Williams D, et al.

Implications of stroke for caregiver outcomes: Findings from the

ASPIRE-S Study. Int J Stroke 2015;10:918–23.

[277] Seeher K, Low L-F, Reppermund S, Brodaty H. Predictors and out-

comes for caregivers of people with mild cognitive impairment: A

systematic literature review. Alzheimers Dement 2013;9:346–55.

[278] Epstein-Lubow G, Gaudiano B, Darling E, Hinckley M, Tremont G,

Kohn R, et al. Differences in depression severity in family care-

givers of hospitalized individuals with dementia and family care-

givers of outpatients with dementia. Am J Geriatr Psychiatry

2012;20:815–9.

[279] Vitaliano PP, Ustundag O, Borson S. Objective and subjective cogni-

tive problems among caregivers and matched non-caregivers. Geron-

tologist 2016;pii:gnv690 [epub ahead of print].

[280] Dassel KB, Carr DC, Vitaliano P. Does caring for a spouse with de-

mentia accelerate cognitive decline? Findings from the Health and

Retirement Study. Gerontologist 2015;pii:gnv148 [epub ahead of

print].

[281] Gillespie R, Mullan J, Harrison L. Managing medications: The role of

informal caregivers of older adults and people living with dementia:

A review of the literature. J Clin Nurs 2014;23:3296–308.

[282] Alsaeed D, Jamieson E, Gul MO, Smith FJ. Challenges to optimal

medicines use in people living with dementia and their caregivers:

A literature review. Int J Pharm 2016;512:396–404.

[283] Rubin R, White-Means S. Informal caregiving: Dilemmas of sand-

wiched caregivers. J Fam Econ Issues 2009;30:252–67.

[284] Chassin L, Macy JT, Seo D-C, Presson CC, Sherman SJ. The associ-

ation between membership in the sandwich generation and health be-

haviors: A longitudinal study. J Appl Dev Psychol 2010;31:38–46.

[285] Do EK, Cohen SA, Brown MJ. Socioeconomic and demographic fac-

tors modify the association between informal caregiving and health in

the Sandwich Generation. BMC Public Health 2014;14:362.

[286] Gaugler JE, Mittelman MS, Hepburn K, Newcomer R. Clinically sig-

nificant changes in burden and depression among dementia care-

givers following nursing home admission. BMC Med 2010;8:85.

[287] Mausbach BT, Chattillion EA, Ho J, Flynn LM, Tiznado D, von

K€anel R, et al. Why does placement of persons with Alzheimer’s dis-

ease into long-term care improve caregivers’ well-being? Examina-

tion of psychological mediators. Psychol Aging 2014;29:776–86.

[288] Peacock SC. The experience of providing end-of-life care to a rela-

tive with advanced dementia: An integrative literature review. Palliat

Support Care 2013;11:155–68.

[289] Schulz R, Mendelsohn AB, Haley WE, Mahoney D, Allen RS,

Zhang S, et al. End-of-life care and the effects of bereavement on

family caregivers of persons with dementia. N Engl J Med 2003;

349:1936–42.

[290] Fonareva I, Oken BS. Physiological and functional consequences of

caregiving for relatives with dementia. Int Psychogeriatr 2014;

26:725–47.

[291] von K€anel R, Mausbach BT, Ancoli-Israel S, Mills PJ, Dimsdale JE, Patterson TL, et al. Positive affect and sleep in spousal Alzheimer

caregivers: A longitudinal study. Behav Sleep Med 2014;12:358–72.

[292] Peng H-L, Chang Y-P. Sleep disturbance in family caregivers of indi-

viduals with dementia: A review of the literature. Perspect Psychiatr

C 2012;49:135–46.

[293] V€alim€aki TH, Martikainen JA, Hongisto K, V€a€at€ainen S, Sintonen H,

Koivisto AM. Impact of Alzheimer’s disease on the family care-

giver’s long-term quality of life: Results from an ALSOVA follow-

up study. Qual Life Res 2016;25:687–97.

[294] Bremer P, Cabrera E, Leino-Kilpi H, Lethin C, Saks K, Sutcliffe C.

Informal dementia care: Consequences for caregivers’ health and health

care use in 8 European countries. Health Policy 2015;119:1459–71.

[295] MetLife Mature Market Institute. The MetLife Study of Alzheimer’s

Disease: The Caregiving Experience; August 2006. Available at:

https://www.metlife.com/assets/cao/mmi/publications/studies/mmi-

alzheimers-disease-caregiving-experience-study.pdf. Accessed

November 24, 2016.

[296] Dassel KB, Carr DC. Does dementia caregiving accelerate frailty?

Findings from the Health and Retirement Study. Gerontologist

2016;56:444–50.

[297] Fredman L, Bertrand RM, Martire LM, Hochberg M, Harris EL. Lei-

sure-time exercise and overall physical activity in older women care-

givers and non-caregivers from the Caregiver-SOF Study. Prev Med

2006;43:226–9.

[298] Roepke SK, Allison M, Von Kanel R, Mausbach BT, Chattillion EA,

Harmell AL, et al. Relationship between chronic stress and carotid

intima-media thickness (IMT) in elderly Alzheimer’s disease care-

givers. Stress 2012;15:121–9.

[299] Gouin J, Glaser R, Malarkey WB, Beversdorf D, Kiecolt-Glaser J.

Chronic stress, daily stressors, and circulating inflammatory markers.

Health Psychol 2012;31:264–8.

[300] von Kanel R, Mills PJ, Mausbach BT, Dimsdale JE, Patterson TL,

Ziegler MG, et al. Effect of Alzheimer caregiving on circulating

levels of C-reactive protein and other biomarkers relevant to cardio-

vascular disease risk: A longitudinal study. Gerontology 2012;

58:354–65.

[301] von Kanel R, Mausbach BT, Dimsdale JE, Mills PJ, Patterson TL,

Ancoli-Israel S, et al. Effect of chronic dementia caregiving and ma-

jor transitions in the caregiving situation on kidney function: A lon-

gitudinal study. Psychosom Med 2012;74:214–20.

[302] Mausbach BT, Chattillion E, Roepke SK, Ziegler MG, Milic M, von

Kanel R, et al. A longitudinal analysis of the relations among stress,

depressive symptoms, leisure satisfaction, and endothelial function in

caregivers. Health Psychol 2012;31:433–40.

[303] Chattillion EA, Mausbach BT, Roepke SK, von Kanel R, Mills PJ,

Dimsdale JE, et al. Leisure activities, caregiving demands and cate-

cholamine levels in dementia caregivers. Psychol Health 2012;

27:1134–49.

[304] von Kanel R, Dimsdale JE, Mills PJ, Ancoli-Israel S, Patterson TL,

Mausbach BT, et al. Effect of Alzheimer caregiving stress and age

on frailty markers interleukin-6, C-reactive protein, and D-dimer. J

Gerontol A Biol Sci Med Sci 2006;61:963–9.

[305] Kiecolt-Glaser JK, Dura JR, Speicher CE, Trask OJ, Galser R.

Spousal caregivers of dementia victims: Longitudinal changes in im-

munity and health. Psychosom Med 1991;53:345–62.

[306] Kiecolt-Glaser JK, Marucha PT, Mercado AM, Malarkey WB,

Glaser R. Slowing of wound healing by psychological stress. Lancet

1995;346:1194–6.

[307] Vitaliano PP, Scanlan JM, Zhang J, Savage MV, Hirsch IB, Siegler I.

A path model of chronic stress, the metabolic syndrome, and coro-

nary heart disease. Psychosom Med 2002;64:418–35.

[308] Shaw WS, Patterson TL, Ziegler MG, Dimsdale JE, Semple SJ,

Grant I. Accelerated risk of hypertensive blood pressure recordings

among Alzheimer caregivers. J Psychosom Res 1999;46:215–27.

[309] Mausbach BT, Roepke SK, Ziegler MG, Milic M, Von Kanel R,

Dimsdale JE, et al. Association between chronic caregiving stress

and impaired endothelial function in the elderly. J Am Coll Cardiol

2010;55:2599–606.

[310] Schubert CC, Boustani M, Callahan CM, Perkins AJ, Hui S,

Hendrie HC. Acute care utilization by dementia caregivers within ur-

ban primary care practices. J Gen Intern Med 2008;23:1736–40.

[311] Zhu CW, Scarmeas N, Ornstein K, Albert M, Brandt J, Blacker D,

et al. Health-care use and cost in dementia caregivers: Longitudinal

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 367

results from the Predictors Caregiver Study. Alzheimers Dement

2015;11:444–54.

[312] Christakis NA, Allison PD. Mortality after the hospitalization of a

spouse. N Engl J Med 2006;354:719–30.

[313] Perkins M, Howard VJ, Wadley VG, Crowe M, Safford MM,

Haley WE, et al. Caregiving strain and all-cause mortality: Evidence

from the REGARDS Study. J Gerontol B Psychol Sci Soc Sci 2013;

68:504–12.

[314] Gitlin LN, Hodgson N. Caregivers as therapeutic agents in dementia

care: The evidence-base for interventions supporting their role. In:

Gaugler JE, Kane RL, eds. Family caregiving in the new normal.

Philadelphia, Pa: Elsevier, Inc.; 2015. p. 305–56.

[315] Maslow K. Translating Innovation to Impact: Evidence-Based Inter-

ventions to Support People with Alzheimer’s Disease and their Care-

giver at Home and in the Community. Washington, D.C.:

Administration on Aging. Available at: http://www.aoa.acl.gov/

AoA_Programs/HPW/Alz_Grants/docs/TranslatingInnovationto

ImpactAlzheimersDisease.pdf; 2012. Accessed November 24,

2016.

[316] Rosalynn Carter Institute for Caregiving. Caregiver Intervention

Database. Available at: http://www.rosalynncarter.org/caregiver_

intervention_database/. Accessed November 24, 2016.

[317] Menne HL, Bass DM, Johnson JD, Primetica B, Kearney KR,

Bollin S, et al. Statewide implementation of “reducing disability in

Alzheimer’s disease”: Impact on family caregiver outcomes. J Geron-

tol Soc Work 2014;57:626–39.

[318] Teri L, McKenzie G, Logsdon RG, McCurry SM, Bollin S, Mead J,

et al. Translation of two evidence-based programs for training fam-

ilies to improve care of persons with dementia. Gerontologist 2012;

52:452–9.

[319] Gitlin LN, Jacobs M, Earland TV. Translation of a dementia care-

giver intervention for delivery in homecare as a reimbursable

Medicare service: Outcomes and lessons learned. Gerontologist

2010;50:847–54.

[320] Burgio LD, Collins IB, Schmid B, Wharton T, McCallum D,

Decoster J. Translating the REACH caregiver intervention for use

by area agency on aging personnel: The REACH OUT program.

Gerontologist 2009;49:103–16.

[321] Mittelman MS, Bartels SJ. Translating research into practice: Case

study of a community-based dementia caregiver intervention. Health

Aff 2014;33:587–95.

[322] Cheung KS, Lau BH, Wong PW, Leung AY, Lou VW, Chan GM, et al.

Multicomponent intervention on enhancing dementia caregiver well-

being and reducing behavioral problems among Hong Kong Chinese:

A translational study based on REACH II. Int J Geriatr Psychiatry

2015;30:460–9.

[323] Samia LW, Aboueissa AM, Halloran J, Hepburn K. The Maine Savvy

Caregiver Project: Translating an evidence-based dementia family

caregiver program within the RE-AIM Framework. J Gerontol Soc

Work 2014;57:640–61.

[324] Lykens K, Moayad N, Biswas S, Reyes-Ortiz C, Singh KP. Impact of

a community based implementation of REACH II program for care-

givers of Alzheimer’s patients. PLoS One 2014;9:e89290.

[325] Menne HL, Bass DM, Johnson JD, Kearney KR, Bollin S, Teri L. Pro-

gram components and outcomes of individuals with dementia: Re-

sults from the replication of an evidence-based program. J Appl

Gerontol 2015;pii:0733464815591212 [epub ahead of print].

[326] Primetica B, Menne HL, Bollin S, Teri L, Molea M. Evidence-Based

Program replication: Translational activities, experiences, and chal-

lenges. J Appl Gerontol 2015;34:652–70.

[327] Fortinsky RH, Gitlin LN, Pizzi LT, Piersol CV, Grady J, Robison JT,

et al. Translation of the Care of Persons with Dementia in their Envi-

ronments (COPE) intervention in a publicly-funded home care

context: Rationale and research design. Contemp Clin Trials 2016;

49:155–65.

[328] Nichols LO, Martindale-Adams J, Burns R, Zuber J, Graney MJ.

REACH VA: Moving from translation to system implementation.

Gerontologist 2016;56:135–44.

[329] Boots LM, de Vugt ME, van Knippenberg RJ, Kempen GI,

Verhey FR. A systematic review of internet-based supportive inter-

ventions for caregivers of patients with dementia. Int J Geriatr Psy-

chiatry 2015;29:331–44.

[330] Czaja SJ, Loewenstein D, Schulz R, Nair SN, Perdomo D. A video-

phone psychosocial intervention for dementia caregivers. Am J Ger-

iatr Psychiatry 2013;21:1071–81.

[331] Griffiths PC, Whitney MK, Kovaleva M, Hepburn K. Development

and implementation of tele-savvy for dementia caregivers: A Depart-

ment of Veterans Affairs Clinical Demonstration Project. Gerontolo-

gist 2016;56:145–54.

[332] Gaugler JE, Potter T, Pruinelli L. Partnering with caregivers. Clin

Geriatr Med 2014;30:493–515.

[333] Gitlin LN, Marx K, Stanley IH, Hodgson N. Translating evidence-

based dementia caregiving interventions into practice: State-of-the-

science and next steps. Gerontologist 2015;55:210–26.

[334] Wethington E, Burgio LD. Translational research on caregiving:

Missing links in the translation process. In: Gaugler JE, Kane RL,

eds. Family caregiving in the new normal. Philadelphia, Pa: Elsevier,

Inc; 2015. p. 193–210.

[335] Zarit SH. Empirically supported treatment for family caregivers. In:

Qualls SH, Zarit SH, eds. Aging families and caregiving. Hoboken,

N.J.: John Wiley & Sons, Inc.; 2009. p. 131–54.

[336] Zarit SH, Lee JE, Barrineau MJ, Whitlatch CJ, Femia EE. Fidelity

and acceptability of an adaptive intervention for caregivers: An

exploratory study. Aging Ment Health 2013;17:197–206.

[337] Van Mierlo LD, Meiland FJ, Van Hout HP, Dr€oes RM. Toward an evidence-based implementation model and checklist for personalized

dementia care in the community. Int Psychogeriatr 2016;28:801–13.

[338] Gaugler JE, Reese M, Tanler R. Care to Plan: An online tool that offers

tailored support to dementia caregivers. Gerontologist 2016;

56:1161–74.

[339] Gonyea JG, L�opez LM, Vel�asquez EH. The effectiveness of a cultur-

ally sensitive cognitive behavioral group intervention for Latino Alz-

heimer’s caregivers. Gerontologist 2016;56:292–302.

[340] Llanque SM, Enriquez M. Interventions for Hispanic caregivers of

patients with dementia: A review of the literature. Am J Alzheimers

Dis Other Demen 2012;27:23–32.

[341] Kally Z, Cote SD, Gonzalez J, Villarruel M, Cherry DL, Howland S,

et al. The Savvy Caregiver Program: Impact of an evidence-based

intervention on the well-being of ethnically diverse caregivers. J Ger-

ontol Soc Work 2014;57:681–93.

[342] Kally Z, Cherry DL, Howland S, Villarruel M. Asian Pacific Islander

dementia care network: A model of care for underserved commu-

nities. J Gerontol Soc Work 2014;57:710–27.

[343] Napoles AM, Chadiha L, Eversley R, Moreno-John G. Reviews:

Developing culturally sensitive dementia caregiver interventions:

Are we there yet? Am J Alzheimers Dis Other Dement 2010;

25:389–406.

[344] Hicken BL, Daniel C, Luptak M, Grant M, Kilian S, Rupper RW.

Supporting caregivers of rural veterans electronically (SCORE). J

Rural Health 2016; http://dx.doi.org/10.1111/jrh.12195 [epub ahead

of print].

[345] Graham-Phillips A, Roth DL, Huang J, Dilworth-Anderson P,

Gitlin LN. Racial and Ethnic Differences in the Delivery of the Re-

sources for Enhancing Alzheimer’s Caregiver Health II Intervention.

J Am Geriatr Soc 2016;64:1662–7.

[346] Khatutsky G, Wiener J, Anderson W, Akhmerova V, Jessup EA,

Squillace MR. Understanding direct care workers: A snapshot of

two of America’s most important jobs: Certified nursing assistants

and home health aides. Washington, DC: U.S. Department of Health

and Human Services; 2011.

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373368

[347] Jones AL, Dwyer LL, Bercovitz AR, Strahan GW. The National

Nursing Home Survey: 2004 Overview. Vital Health Stat 13 2009;

167:1–155.

[348] Kramer NA, Smith MC. Training nursing assistants to care for

nursing home residents with dementia. In: Molinari V, ed. Profes-

sional psychology in long- term care. New York, N.Y.: Hatherleigh

Press; 2000. p. 227–56.

[349] McCabe MP, Davison TE, George K. Effectiveness of staff training

programs for behavioral problems among older people with demen-

tia. Aging Ment Health 2007;11:505–19.

[350] Beck C, Ortigara A, Mercer S, Shue V. Enabling and empowering

certified nursing assistants for quality dementia care. Int J Geriatr

Psychiatry 1999;14:197–211.

[351] Institute of Medicine. Retooling for an Aging America: Building the

Health Care Workforce. Washington, D.C.: The National Academies

Press. Available at: https://www.nationalacademies.org/hmd/w/ media/Files/Report%20Files/2008/Retooling-for-an-Aging-America-

Building-the-Health-Care-Workforce/ReportBriefRetoolingforan

AgingAmericaBuildingtheHealthCareWorkforce.pdf; 2008. Accessed

November 30, 2016.

[352] Stone RI. Factors affecting the future of family caregiving in

the United States. In: Gaugler JE, Kane RL, eds. Family

caregiving in the new normal. San Diego, CA: Elsevier, Inc; 2015.

p. 57–77.

[353] Elvish R, Burrow S, Cawley R, Harney K, Pilling M, Gregory J, et al.

’Getting to know me’: The second phase roll-out of a staff training pro-

gramme for supporting people with dementia in general hospitals. De-

mentia (London) 2016;pii:1471301216634926 [epub ahead of print].

[354] Spector A, Orrell M, Goyder J. A systematic review of staff training

interventions to reduce the behavioural and psychological symptoms

of dementia. Ageing Res Rev 2013;12:354–64.

[355] Bray J, Evans S, Bruce M, Carter C, Brooker D, Milosevic S, et al.

Enabling hospital staff to care for people with dementia. Nurs Old

People 2015;27:29–32.

[356] Palmer JL, Lach HW, McGillick J, Murphy-White M, Carroll MB,

Armstrong JL. The Dementia Friendly Hospital Initiative education

program for acute care nurses and staff. J Contin Educ Nurs 2014;

45:416–24.

[357] Surr CA, Smith SJ, Crossland J, Robins J. Impact of a person-centred

dementia care training programme on hospital staff attitudes, role ef-

ficacy and perceptions of caring for people with dementia: A repeated

measures study. Int J Nurs Stud 2016;53:144–51.

[358] Eldercare Workforce Alliance. Geriatrics Workforce Shortage: A

Looming Crisis for our Families. Wash D.C.: Eldercare Workforce

Alliance; 2012.

[359] The American Geriatrics Society. The Geriatrics Workforce Policy

Studies Center (GWPS). Available at: http://www.americangeriatrics.org/

advocacy_public_policy/gwps/gwps_faqs/id:3188. Accessed November

24, 2016.

[360] Hoffman D, Zucker H. A call to preventive action by health care pro-

viders and policy makers to support caregivers. Prev Chronic Dis

2016;13:E96.

[361] Adelman RD, Tmanova LL, Delgado D, Dion S, Lachs MS. Care-

giver burden: A clinical review. JAMA 2014;311:1052–60.

[362] Riedel O, Klotsche J, Wittchen HU. Overlooking informal dementia

caregivers’ burden. Res Gerontol Nurs 2016;9:167–74.

[363] Alzheimer’s Association National Plan Care and Support Milestone

Workgroup, Borson S, Boustani MA, Buckwalter KC, Burgio LD,

Chodosh J, et al. Report on milestones for care and support under

the U.S. National Plan to Address Alzheimer’s Disease. Alzheimers

Dement 2016;12:334–69.

[364] Gaugler JE, Westra BL, Kane RL. Professional discipline and support

recommendations for family caregivers of persons with dementia. Int

Psychogeriatr 2016;28:1029–40.

[365] Austrom MG, Carvell CA, Alder CA, Gao S, Boustani M,

LaMantia M. Workforce development to provide person-centered

care. Aging Ment Health 2016;20:781–92.

[366] Brody AA, Galvin JE. A review of interprofessional dissemination

and education interventions for recognizing and managing dementia.

Gerontol Geriatr Educ 2013;34:225–56.

[367] McCaffrey R, Tappen RM, Lichtstein DM, Friedland M. Interprofes-

sional education in community-based Alzheimer’s disease diagnosis

and treatment. J Interprof Care 2013;27:534–6.

[368] K€ohler L, Meinke-Franze C, Hein J, Fendrich K, Heymann R, Thyrian JR, et al. Does an interdisciplinary network improve demen-

tia care? Results from the IDemUck-study. Curr Alzheimer Res 2014;

11:538–48.

[369] Sadak T, Wright J, Borson S. Managing Your Loved One’s Health:

Development of a new care management measure for dementia fam-

ily caregivers. J Appl Gerontol 2016;pii:0733464816657472 [epub

ahead of print].

[370] Noel MA, Kaluzynski TS, Templeton VH. Quality dementia care:

Integrating caregivers into a chronic disease management model. J

Appl Gerontol 2015;pii:0733464815589986 [epub ahead of print].

[371] Tan ZS, Jennings L, Reuben D. Coordinated care management for de-

mentia in a large academic health system. Health Aff 2014;

33:619–25.

[372] Callahan CM, Sachs GA, Lamantia MA, Unroe KT, Arling G,

Boustani MA. Redesigning systems of care for older adults with Alz-

heimer’s disease. Health Aff 2014;33:626–32.

[373] French DD, LaMantia MA, Livin LR, Herceg D, Alder CA,

Boustani MA. Healthy Aging Brain Center improved care coordina-

tion and produced net savings. Health Aff 2014;33:613–8.

[374] Borson S, Chodosh J. Developing dementia-capable health care sys-

tems: A 12-step program. Clin Geriatr Med 2014;30:395–420.

[375] Reuben DB, Evertson LC, Wenger NS, Serrano K, Chodosh J,

Ercoli L, et al. The University of California at Los Angeles Alz-

heimer’s and Dementia Care Program for comprehensive, coordi-

nated, patient-centered care: Preliminary data. J Am Geriatr Soc

2013;61:2214–8.

[376] Odenheimer G, Borson S, Sanders AE, Swain-Eng RJ, Kyomen HH,

Tierney S, et al. Quality improvement in neurology: Dementia man-

agement quality measures (executive summary). Am J Occup Ther

2013;67:704–10.

[377] LaMantia MA, Alder CA, Callahan CM, Gao S, French DD,

Austrom MG, et al. The Aging Brain Care Medical Home: Prelimi-

nary data. J Am Geriatr Soc 2015;63:1209–13.

[378] National Academies of Sciences, Engineering, and Medicine. Fam-

ilies Caring for an Aging America. Washington, D.C.: The National

Academies Press; 2016.

[379] Gaugler JE, Kane RL, eds. Family caregiving in the new normal.

Philadelphia, Pa: Elsevier, Inc.; 2015.

[380] Unpublished tabulations based on data from the Medicare Current

Beneficiary Survey for 2011. Prepared under contract by Avalere

Health, 2016.

[381] Yang Z, Zhang K, Lin PJ, Clevenger C, Atherly A. A longitudinal

analysis of the lifetime cost of dementia. Health Serv Res 2012;

47:1660–78.

[382] Yang Z, Levey A. Gender differences: A lifetime analysis of the eco-

nomic burden of Alzheimer’s disease. Women Health Iss 2015;

25:436–40.

[383] Kelley AS, McGarry K, Gorges R, Skinner JS. The burden of health

care costs for patients with dementia in the last 5 years of life. Ann

Intern Med 2015;163:729–36.

[384] Bynum JPW, Meara E, Chang C-H, Rhoads JM. Our Parents, Our-

selves: Health Care for an Aging Population. A Report of the Dart-

mouth Atlas Project. The Dartmouth Institute for Health Policy &

Clinical Practice. 2016.

[385] Rudolph JL, Zanin NM, Jones RN, Marcantonio ER, Fong TG,

Yang FM, et al. Hospitalization in community-dwelling persons

with Alzheimer’s disease: Frequency and causes. J Am Geriatr Soc

2010;58:1542–8.

[386] Beydoun MA, Beydoun HA, Gamaldo AA, Rostant O, Dore GA,

Zonderman AB, et al. Nationwide Inpatient Prevalence, Predictors

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 369

and Outcomes of Alzheimer’s Disease Among Older Adults in the

United States, 2002–2012. J Alzheimers Dis 2015;48:361–75.

[387] Medicare. Glossary. Medicare: The Official U.S. Government Site for

Medicare. Available at: http://www.medicare.gov/HomeHealthCompare/

Resources/Glossary.html. Accessed November 24, 2016.

[388] Leibson CL, Hall Lon K, Ransom JE, Robers RO, Hass SL,

Duhig AM, et al. Direct medical costs and source of cost differences

across the spectrum of cognitive decline: A population-based study.

Alzheimers Dement 2015;11:917–32.

[389] Suehs BT, Davis CD, Alvir J, van Amerongen D, Patel NC, Joshi AV,

et al. The clinical and economic burden of newly diagnosed Alz-

heimer’s disease in a Medicare Advantage population. Am J Alz-

heimers Dis Other Demen 2013;28:384–92.

[390] Lin P-J, Zhon Y, Fillit HM, Chen E, Neumann PJ. Medicare expen-

ditures of individuals with Alzheimer’s disease and related dementias

or mild cognitive impairment before and after diagnosis. JAm Geriatr

Soc 2016;64:1549–57.

[391] Geldmacher DS, Kirson NY, Birnbaum HG, Eapen S, Kantor E,

Cummings AK, et al. Pre-diagnosis excess acute care costs in Alz-

heimer’s patients among a U.S. Medicaid population. Appl Health

Econ Health Policy 2013;11:407–13.

[392] Zhu CW, CosentinoS, Ornstein K, Gu Y, ScarmeasN, Andrews H, etal.

Medicare utilization and expenditures around incident dementia in a

multiethnic cohort. J Gerontol A Biol Sci Med Sci 2015;70:1448–53.

[393] Kirson NY, Desai U, Ristovska L, Cummings AKG, Birnbaum HG,

Ye W, et al. Assessing the economic burden of Alzheimer’s disease

patients first diagnosed by specialists. BMC Geriatr 2016;16:138.

[394] Stark SL, Roe CM, Grant EA, Hollingsworth H, Benzinger TL,

Fagan AM, et al. Preclinical Alzheimer’s disease and risk of falls.

Neurology 2013;81:437–43.

[395] Genworth. Cost Care Surv 2016: Summary of 2016 Survey Findings.

Available at: https://www.genworth.com. Accessed October 1, 2016.

[396] Johnson RW, Wiener JM. A Profile of Frail Older Americans and

Their Caregivers. Washington, D.C.: Urban Institute; 2006.

[397] Dwyer LL, Harris-Kojetin LD, Valverde RH. Differences in Adult

Day Services Center Participant Characteristics by Center Owner-

ship: United States, 2012. NCHS Data Brief, No 2014;164.

[398] Dwyer LL, Harris-Kojetin LD, Valverde RH. Differences in Adult

Day Services Center Characteristics by Center Ownership: United

States, 2012. NCHS Data Brief, No 2014;165.

[399] Mollica R, Houser A, Ujvari K. Assisted Living and Residential Care in

the States in 2010. Washington, D.C.: AARP Public Policy Institute;

2012.

[400] Sengupta M, Harris-Kojetin LD, Caffrey C. Variation in Residential

Care Community Resident Characteristics, by Size of Commnity:

United States, 2014. NCHS Data Brief, No 2015;223.

[401] Caffrey C, Harris-Kojetin L, Rome V, Sengupta M. Variation in Oper-

ating Characteristics of Residential Care Communities by Size of

Community: United States, 2014. NCHS Data Brief, No 2015;222.

[402] U.S. Centers for Medicare & Medicaid Services. Nurs Home Data

Compend 2015 Edition. Available at: https://www.cms.gov/Medi

care/Provider-Enrollment-and-Certification/CertificationandComplianc/

Downloads/nursinghomedatacompendium_508-2015.pdf. Accessed

December 13, 2016.

[403] American Health Care Association. LTC Stats: Nursing Facility

Operational Characteristics Report. Table 5: Nurs Facility Beds Dedi-

cated Spec Care Units; 2014.

[404] American Health Care Association. LTC Stats: Nursing Facility

Operational Characteristics Report. Table 5: Nurs Facility Beds Dedi-

cated Spec Care Units; 2013.

[405] Bynum J. Characteristics, Costs, and Health Service Use for Medi-

care Beneficiaries with a Dementia Diagnosis: Report 1: Medicare

Current Beneficiary Survey. Unpublished; provided under contract

with the Alzheimer’s Association. Lebanon, N.H.: Dartmouth Insti-

tute for Health Policy and Clinical Care, Center for Health Policy

Research; 2009.

[406] Eiken S, Sredl K, Burwell B, Saucier P. Medicaid Expenditures for

Long-Term Services and Supports (LTSS) in FY 2014: Managed

LTSS Reached 15 Percent of LTSS Spending. Chicago, Ill.: Truven

Health Analytics; 2016.

[407] Callahan CM, Arling G, Tu W, Rosenman MB, Counsell SR,

Stump TE, et al. Transitions in care among older adults with and

without dementia. J Am Geriatr Soc 2012;60:813–20.

[408] Gozalo P, Teno JM, Mitchell SL, Skinner J, Bynum J, Tyler D, et al.

End-of-life transitions among nursing home residents with cognitive

issues. N Engl J Med 2011;365:1212–21.

[409] Teno JM, Mitchell SL, Skinner J, Kuo S, Fisher E, Intrator O, et al.

Churning: The association between health care transitions and

feeding tube insertion for nursing home residents with advanced

cognitive impairment. J Palliat Med 2009;12:359–62.

[410] MetLife Mature Market Institute. Market Survey of Long-Term Care

Costs: The 2012 MetLife Market Survey of Nursing Home, Assisted

Living, Adult Day Services, and Home Care Costs. New York, N.Y.:

Metropolitan Life Insurance Company; 2012.

[411] Jacobson G, Swoope C, Neuman T. Income and Assets of Medicare

Beneficiaries, 2014-2030. The Henry J. Kaiser Family Foundation

Issue Brief; 2015.

[412] U.S. Department of Health and Human Services. What is Long-Term

Care Insurance? Available at: http://longtermcare.gov/costs-how-

to-pay/what-is-long-term-care-insurance/.AccessedNovember272016.

[413] U.S. Centers for Medicare & Medicaid Services. Your Medicare

Coverage. Long-Term Care. Available at: https://www.medicare.

gov/coverage/long-term-care.html. Accessed December 20, 2016.

[414] Association of Health Insurance Plans. AHIP Statement on Long-

Term Care Insurance. Available at: https://www.ahip.org/ahip-statement-

on-long-term-care-insurance/. Accessed 2016.

[415] Cohen MA. “The Current State of the Long-Term Care Insurance Mar-

ket.” Presented to the 14th Annual Intercompany Long-Term Care In-

surance Conference. March 2014. Available at: http://iltciconf.org/

2014/index_htm_files/44-Cohen.pdf. Accessed November 24, 2016.

[416] HHS Office of the Assistant Secretary for Planning and Evaluation

Office of Disability, Aging and Long-Term Care Policy. Long-term

Care Insurance ASPE Res Brief. 2012.

[417] Reaves EL, Musumeci M. Medicaid and Long-Term Services and

Supports: A Primer. Menlo Park, Calif.: Kaiser Commission on

Medicaid and the Uninsured, Henry J. Kaiser Family Foundation;

2015. Publication # 8617–02.

[418] Moody’s Investors Service. Special Comment: Long-Term Care In-

surance: Sector Profile; 2012.

[419] U.S. Centers for Medicare & Medicaid Services. Medicare Provider

Utilization and Payment Data: Hospice Providers. Available at:

https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-

Trends-and-Reports/Medicare-Provider-Charge-Data/Hospice.html.

Accessed November 5, 2016.

[420] U.S. Centers for Medicare and Medicaid Services. Hospice Center.

Available at: http://www.cms.gov/Medicare/Medicare-Fee-for-Service-

Payment/Hospice/Medicare_Hospice_Data.html. Accessed November

24, 2016.

[421] Miller SC, Lima JC, Looze J, Mitchell SL. Dying in U.S. nursing

homes with advanced dementia: How does health care use differ

for residents with, versus without, end-of-life Medicare skilled

nursing facility care? J Palliat Med 2012;15:43–50.

[422] Miller SC, Gozalo P, Mor V. Hospice enrollment and hospitalization

of dying nursing home patients. Am J Med 2001;11:38–44.

[423] Kiely DK, Givens JL, Shaffer ML, Teno JM, Mitchell SL. Hospice

use and outcomes in nursing home residents with advanced dementia.

J Am Geriatr Soc 2010;58:2284–91.

[424] Miller SC, Mor V, Wu N, Gozalo P, Lapane K. Does receipt of hos-

pice care in nursing homes improve management of pain at the end of

life? J Am Geriatr Soc 2002;50:507–15.

[425] Teno JM, Gozalo PL, Bynum JP, Leland NE, Miller SC, Morden NE,

et al. Change in end-of-life care for Medicare beneficiaries: Site of

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373370

death, place of care, and health care transitions in 2000, 2005, and

2009. JAMA 2013;390:470–7.

[426] Shega JW, Hougham GW, Stocking CB, Cox-Hayley D, Sachs GA.

Patients dying with dementia: Experience at the end of life

and impact of hospice care. J Pain Symptom Manage 2008;

35:499–507.

[427] Teno JM, Meltzer DO, Mitchell SL, Fulton AT, Gozalo P, Mor V.

Type of attending physician influenced feeding tube insertions for

hospitalized elderly people with severe dementia. Health Aff 2014;

33:675–82.

[428] Mitchell SL, Mor V, Gozalo PL, Servadio JL, Teno JM. Tube feeding

in U.S. nursing home residents with advanced dementia, 2000-2014.

JAMA 2016;316:769–70.

[429] Gozalo P, Plotzke M, Mor V, Miller SC, Teno JM. Changes in Medi-

care costs with the growth of hospice care in nursing homes. N Engl J

Med 2015;372:1823–31.

[430] Gilligan AM, Malone DC, Warholak TL, Armstrong EP. Health dis-

parities in cost of care in patients with Alzheimer’s disease: An anal-

ysis across 4 state Medicaid populations. Am J Alzheimers Dis Other

Dement 2013;28:84–92.

[431] Healthy People 2020. Dementias Including Alzheimer’s Disease.

Available at: http://www.healthypeople.gov/2020/topics-objectives/

topic/dementias-including-alzheimers-disease/national-snapshot. Ac-

cessed November 24, 2016.

[432] Davydow DS, Zibin K, Katon WJ, Pontone GM, Chwastiak L,

Langa KM, et al. Neuropsychiatric disorders and potentially prevent-

able hospitalizations in a prospective cohort study of older Ameri-

cans. J Gen Intern Med 2014;29:1362–71.

[433] Patel A, Parikh R, Howell EH, Hsich E, Landers SH,

Gorodeski EZ. Mini-Cog performance: Novel marker of post

discharge risk among patients hospitalized for heart failure. Circ

Heart Fail 2015;8:8–16.

[434] Lin PJ, Fillit HM, Cohen JT, Neumann PJ. Potentially avoidable

hospitalizations among Medicare beneficiaries with Alzheimer’s

disease and related disorders. Alzheimers Dement 2013;9:30–8.

Appendices: End notes

A1Six drugs approved by the U.S. Food and Drug Admin- istration (FDA): The FDA has approved six drugs to alle- viate symptoms of Alzheimer’s dementia: tacrine (discontinued in the United States due to potentially severe side effects), galantamine, rivastigmine, donepezil, meman- tine, and a drug that combines memantine and donepezil. None of these drugs slows or stops the progression of Alz- heimer’s disease.

A2Number of Americans age 65 and older with Alz- heimer’s dementia for 2017 (prevalence of Alzheimer’s in 2017): The number 5.3 million is from published prevalence estimates based on incidence data from the Chicago Health and Aging Project (CHAP) and population estimates from the 2010 U S. Census [31].

A3Proportion of Americans age 65 and older with Alz- heimer’s dementia: The 10 percent for the age 65 and older population is calculated by dividing the estimated number of people age 65 and older with Alzheimer’s dementia (5.3 million) by the U.S. population age 65 and older in 2017, as projected by the U.S. Census Bureau (51.1 million) 5 approximately 10 percent [437]. Please note that the proportion of Americans age 65 and older

[435] Feng Z, Coots LA, Kaganova Y, Wiener JM. Hospital and ED use

among Medicare beneficiaries with dementia varies by setting and

proximity to death. Health Aff 2014;33:683–90.

[436] Amjad H, Carmicheal D, Austin AM, Chang C-H, Bynum JPW. Con-

tinuity of care and health care utilization in older adults. JAMA Intern

Med 2016;176:1371–8.

[437] U.S. Census Bureau. 2014 National Population Projections: Download-

able Files. Available at: https://www.census.gov/population/projections/

data/national/2014/downloadablefiles.html. Accessed 2016.

[438] U.S. Census Bureau. National Population Projections for 2016 to

2020:SummaryTables.Availableat:http://www.census.gov/population/

projections/files/natproj/summary/np-t4-e.pdf. Accessed November 30,

2016.

[439] Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease

in the United States and the public health impact of delaying disease

onset. Am J Public Health 1998;88:1337–42.

[440] National Alliance for Caregiving and AARP, Caregiving in the U.S.,

November 2009. Available at: http://assets.aarp.org/rgcenter/il/

caregiving_09_fr.pdf. Accessed November 24, 2016.

[441] Amo PS, Levine C, Memmott MM. The economic value of informal

caregiving. Health Aff 1999;18:182–8.

[442] U.S. Department of Labor, Bureau of Labor Statistics. Employment,

Hours, Earnings Curr Employment Stat Surv. Series 10-CEU

6562160008, Home Health Care Services (NAICS code 6216),

Average Hourly Earnings, July 2016. Available at: www.bls.gov/

ces. Accessed January 14, 2017.

[443] Albert SM, Schulz R. The MetLife Study of working caregivers and

employer health care costs. New York, N.Y.: MetLife Mature Market

Institute; 2010.

[444] U.S. Centers for Medicare & Medicaid Services, Center for

Strategic Planning, Health Expenditures by State of Residence

1991-2009. Available at: https://www.cms.gov/mmrr/Downloads/

MMRR2011_001_04_a03-.pdf. Accessed November 30, 2016.

[445] Shriver M. The Shriver Report: A Woman’s Nation Takes on Alz-

heimer’s. Chicago, Ill.: Alzheimer’s Association; 2010.

with Alzheimer’s dementia has gone down slightly in recent years despite the number of Americans with Alzheimer’s de- mentia in this age range going up; this is because of the large number of baby boomers who have started to enter this age range and increased the overall number of seniors, but at the early, low-risk years in this range [206].

A4 Percentage of total Alzheimer’s dementia cases by age

groups: Percentages for each age group are based on the esti- mated 200,000 people under 65 [31], plus the estimated numbers for people ages 65 to 74 (0.9 million), 75 to 84 (2.4 million), and 851 (2.1 million) based on prevalence es- timates for each age group and incidence data from the CHAP study. Prevalence numbers for age groups do not total 5.5 million due to rounding.

A5 Differences between CHAP and ADAMS estimates for

Alzheimer’s dementia prevalence: ADAMS estimated the prevalence of Alzheimer’s dementia to be lower than CHAP, at 2.3 million Americans age 71 and older in 2002 [138], while the CHAP estimate for 2000 was 4.5 million [207]. At a 2009 conference convened by the National Insti- tute on Aging and the Alzheimer’s Association, researchers determined that this discrepancy was mainly due to two dif- ferences in diagnostic criteria: (1) a diagnosis of dementia in ADAMS required impairments in daily functioning and

(2) people determined to have vascular dementia in ADAMS were not also counted as having Alzheimer’s, even if they exhibited clinical symptoms of Alzheimer’s [139]. Because the more stringent threshold for dementia in ADAMS may miss people with mild Alzheimer’s demen- tia and because clinical-pathologic studies have shown that mixed dementia due to both Alzheimer’s and vascular pa- thology in the brain is very common [6], the Association be- lieves that the larger CHAP estimates may be a more relevant estimate of the burden of Alzheimer’s dementia in the United States.

A6Number of women and men age 65 and older with Alz- heimer’s dementia in the United States: The estimates for the number of U.S. women (3.3 million) and men (2.0 million) age 65 and older with Alzheimer’s in 2013 is from unpub- lished data from CHAP. For analytic methods, see Hebert et al. [31].

A7Prevalence of Alzheimer’s and other dementias in older whites, African-Americans and Hispanics: The statement that African-Americans are twice as likely and Hispanics one and one-half times as likely as whites to have Alz- heimer’s or other dementias is the conclusion of an expert re- view of a number of multiracial and multi-ethnic data sources, as reported in detail in the Special Report of the Alzheimer’s Association’s 2010 Alzheimer’s Disease Facts and Figures.

A8State-by-state prevalence of Alzheimer’s dementia: These state-by-state prevalence numbers are based on an analysis of incidence data from CHAP, projected to each state’s population, with adjustments for state-specific age, gender, years of education, race and mortality [189]. Specific prevalence numbers projected for each year from 2014 to 2025 derived from this analysis were provided to the Alz- heimer’s Association by a team led by Liesi Hebert, Sc.D., from Rush University Institute on Healthy Aging.

A9Number of new cases of Alzheimer’s dementia this year (incidence of Alzheimer’s in 2017): The East Boston Established Populations for Epidemiologic Study of the Elderly (EPESE) estimated that there would be 454,000 new cases in 2010 and 491,000 new cases in 2020 (see He- bert et al [190]). The Alzheimer’s Association calculated the incidence of new cases in 2017 by multiplying the 10-year change from 454,000 to 491,000 (37,000) by 0.7 (for the number of years from 2010 to 2017 divided by the number of years from 2010 to 2020), adding that result (25,900) to the Hebert et al. estimate for 2010 (454,000) 5 479,900 [190]. Rounded to the nearest thou- sand, this is 480,000 new cases of Alzheimer’s dementia in 2017. The same technique for linear interpolation from 2010 to 2020 projections was used to calculate the number of new cases in 2017 for ages 65-74, 75-84 and 85 and older. The age group-specific Alzheimer’s dementia inci- dent rate is the number of new people with Alzheimer’s per population at risk (the total number of people in the age group in question). These incidence rates are expressed as number of new cases per 1000 people using the total

number of people per age group (e.g., 65-74, 75-84, 851) for 2017 from population projections from the 2000 U S. Census as the denominator [438].

A10Number of seconds for the development of a new case of Alzheimer’s dementia: Although Alzheimer’s does not present suddenly like stroke or heart attack, the rate at which new cases develop can be computed in a similar way. The 66 seconds number is calculated by dividing the number of seconds in a year (31,536,000) by the number of new cases in a year (479,900)A9 5 65.7 seconds, rounded to 66 seconds. Using the same method of calculation for 2050, 31,536,000 divided by 959,000 (from Hebert et al. [190]) 5 32.8 seconds, rounded to 33 seconds.

A11Criteria for identifying people with Alzheimer’s or other dementias in the Framingham Study: From 1975 to 2009, 7901 people from the Framingham Study who had sur- vived free of dementia to at least age 45, and 5937 who had survived free of dementia until at least age 65, were followed for incidence of dementia [160]. Diagnosis of dementia was made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria and required that the participant survive for at least 6 months af- ter onset of symptoms. Standard diagnostic criteria (the NINCDS-ADRDA criteria from 1984) were used to diag- nose Alzheimer’s dementia. The definition of Alzheimer’s and other dementias used in the Framingham Study was very strict; if a definition that included milder disease and disease of less than six months’ duration were used, lifetime risks of Alzheimer’s and other dementias would be higher than those estimated by this study.

A12Projected number of people with Alzheimer’s demen- tia: This figure comes from the CHAP study [31]. Other pro- jections are somewhat lower (see, for example, Brookmeyer et al. [439]) because they relied on more conservative methods for counting people who currently have Alz- heimer’s dementia.A5 Nonetheless, these estimates are sta- tistically consistent with each other, and all projections suggest substantial growth in the number of people with Alz- heimer’s dementia over the coming decades.

A13Projected number of people age 65 and older with Alzheimer’s dementia in 2025: The number 7.1 million is based on a linear extrapolation from the projections of prevalence of Alzheimer’s for the years 2020 (5.8 million) and 2030 (8.4 million) from CHAP [31].

A14Previous high and low projections of Alzheimer’s de- mentia prevalence in 2050: High and low prevalence projec- tions for 2050 from the U.S. Census were not available for the most recent analysis of CHAP data [31]. The previous high and low projections indicate that the projected number of Americans with Alzheimer’s in 2050 age 65 and older will range from 11 to 16 million [207].

A15Annual mortality rate due to Alzheimer’s disease by state: Unadjusted death rates are presented rather than age- adjusted death rates in order to provide a clearer depiction of the true burden of mortality for each state. States such as Florida with larger populations of older people will

Alzheimer’s Association / Alzheimer’s & Dementia 13 (2017) 325–373 371

have a larger burden of mortality due to Alzheimer’s— a burden that appears smaller relative to other states when the rates are adjusted for age.

A16Number of family and other unpaid caregivers of peo- ple with Alzheimer’s or other dementias: To calculate this number, the Alzheimer’s Association started with data from the BRFSS survey. In 2009, the BRFSS survey asked respondents age 18 and over whether they had provided any regular care or assistance during the past month to a fam- ily member or friend who had a health problem, long-term illness or disability. To determine the number of family and other unpaid caregivers nationally and by state, we applied the proportion of caregivers nationally and for each state from the 2009 BRFSS (as provided by the CDC, Healthy Aging Program, unpublished data) to the number of people age 18 and older nationally and in each state from the U.S. Census Bureau report for July 2016. Available at: http://www.census.gov/programs-surveys/popest/data/ tables.html. Accessed Jan. 4, 2017. To calculate the propor- tion of family and other unpaid caregivers who provide care for a person with Alzheimer’s or another dementia, the Alz- heimer’s Association used data from the results of a national telephone survey conducted in 2009 for the National Alli- ance for Caregiving (NAC)/AARP [440]. The NAC/AARP survey asked respondents age 18 and over whether they were providing unpaid care for a relative or friend age 18 or older or had provided such care during the past 12 months. Respondents who answered affirmatively were then asked about the health problems of the person for whom they pro- vided care. In response, 26 percent of caregivers said that: (1) Alzheimer’s or another dementia was the main problem of the person for whom they provided care, or (2) the person had Alzheimer’s or other mental confusion in addition to his or her main problem. The 26 percent figure was applied to the total number of caregivers nationally and in each state, resulting in a total of 15.975 million Alzheimer’s and de- mentia caregivers.

A17The 2014 Alzheimer’s Association Women and Alz- heimer’s Poll: This poll questioned a nationally representa- tive sample of 3102 American adults about their attitudes, knowledge and experiences related to Alzheimer’s and de- mentia from Jan. 9, 2014, to Jan. 29, 2014. An additional 512 respondents who provided unpaid help to a relative or friend with Alzheimer’s or a related dementia were asked questions about their care provision. Random selections of telephone numbers from landline and cell phone exchanges throughout the United States were conducted. One individ- ual per household was selected from the landline sample, and cell phone respondents were selected if they were 18 years old or older. Interviews were administered in En- glish and Spanish. The poll “oversampled” Hispanics, selected from U.S. Census tracts with higher than an 8 percent concentration of this group. A list sample of Asian-Americans was also utilized to oversample this group. A general population weight was used to adjust for number of adults in the household and telephone usage; the second

stage of this weight balanced the sample to estimated U.S. population characteristics. Aweight for the caregiver sample accounted for the increased likelihood of female and white respondents in the caregiver sample. Sampling weights were also created to account for the use of two supplemental list samples. The resulting interviews comprise a probability-based, nationally representative sample of U.S. adults. A caregiver was defined as an adult over age 18 who, in the past 12 months, provided unpaid care to a relative or friend age 50 or older with Alzheimer’s or another demen- tia. Questionnaire design and interviewing were conducted by Abt SRBI of New York.

A18Number of hours of unpaid care: To calculate this number, the Alzheimer’s Association used data from a follow-up analysis of results from the 2009 NAC/AARP na- tional telephone survey (data provided under contract by Matthew Greenwald and Associates, Nov. 11, 2009). These data show that caregivers of people with Alzheimer’s or other dementias provided an average of 21.9 hours a week of care, or 1139 hours per year. The number of family and other unpaid caregivers (15.975 million)A16 was multiplied by the average hours of care per year, which totals 18.191 billion hours of care. This is slightly higher than the total resulting from multiplying 18.191 billion by 15.975 million because 15.975 is a rounded figure for the total number of caregivers.

A19Value of unpaid caregiving: To calculate this number, the Alzheimer’s Association used the method of Amo et al. [441] This method uses the average of the federal minimum hourly wage ($7.25 in 2016) and the mean hourly wage of home health aides ($18.05 in July 2016) [442]. The average is $12.65, which was multiplied by the number of hours of unpaid care (18.191 billion) to derive the total value of un- paid care ($230.127 billion; this is slightly higher than the total resulting from multiplying $12.65 by 18.191 billion because 18.191 is a rounded number for the hours of unpaid care).

A20Higher health care costs of Alzheimer’s caregivers: This figure is based on a methodology originally developed by Brent Fulton, Ph.D., for The Shriver Report: AWoman’s Nation Takes on Alzheimer’s. A survey of 17,000 em- ployees of a multinational firm based in the United States estimated that caregivers’ health care costs were 8 percent higher than non-caregivers’ [443]. To determine the dollar amount represented by that 8 percent figure nationally and in each state, the 8 percent figure and the proportion of caregivers from the 2009 BRFSSA16 were used to weight each state’s caregiver and non-caregiver per capita personal health care spending in 2009 [444], inflated to 2016 dollars. The dollar amount difference between the weighted per capita personal health care spending of caregivers and non-caregivers in each state (reflecting the 8 percent higher costs for caregivers) produced the average additional health care costs for caregivers in each state. Nationally, this translated into an average of $680. The amount of the addi- tional cost in each state, which varied by state from a low of

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$501 in Utah to a high of $1037 in the District of Columbia, was multiplied by the total number of unpaid Alzheimer’s and dementia caregivers in that stateA16 to arrive at that state’s total additional health care costs of Alzheimer’s and other dementia caregivers as a result of being a care- giver. The combined total for all states was $10.852 billion. Fulton concluded that this is “likely to be a conservative es- timate because caregiving for people with Alzheimer’s is more stressful than caregiving for most people who don’t have the disease.” [445].

A21Lewin Model on Alzheimer’s and dementia costs: These numbers come from a model created for the Alzheimer’s Association by the Lewin Group. The model estimates total payments for health care, long-term care and hospice—as well as state-by-state Medicaid spending—for people with Alzheimer’s and other dementias. The model was updated by the Lewin Group in January 2015 (updating previous model) and June 2015 (addition of state-by-state Medicaid es- timates). Detailed information on the model, its long-term projections and its methodology are available at alz.org/ trajectory. For the purposes of the data presented in this report, the following parameters of the model were changed relative to the methodology outlined at alz.org/trajectory: (1) cost data from the 2011 Medicare Current Beneficiary Survey (MCBS) were used rather than data from the 2008 MCBS; (2) preva- lence among older adults was assumed to equal the prevalence levels from Hebert et al [31] and included in this report (5.3 million in 2017),A2 rather than the prevalence estimates derived by the model itself; (3) estimates of inflation and excess cost growth reflect the most recent relevant estimates from the cited sources (the Centers for Medicare & Medicaid Services [CMS] actuaries and the Congressional Budget Of- fice); and (4) the most recent (2014) state-by-state data from CMS on the number of nursing home residents and per- centage with moderate and severe cognitive impairment were used in lieu of 2012 data.

A22All cost estimates were inflated to year 2016 dollars us- ing the Consumer Price Index (CPI): All cost estimates were inflated using the seasonally adjusted average prices for med- ical care services from all urban consumers. The relevant item within medical care services was used for each cost element. For example, the medical care item within the CPI was used to inflate total health care payments; the hospital services item within the CPI was used to inflate hospital payments; and the nursing home and adult day services item within the CPI was used to inflate nursing home payments.

A23Medicare Current Beneficiary Survey Report: These data come from an analysis of findings from the 2011 Medi- care Current Beneficiary Survey (MCBS). The analysis was conducted for the Alzheimer’s Association by Avalere Health [380]. The MCBS, a continuous survey of a nationally repre- sentative sample of about 15,000 Medicare beneficiaries, is linked to Medicare claims. The survey is supported by the U.S. Centers for Medicare & Medicaid Services. For community-dwelling survey participants, MCBS interviews are conducted in person three times a year with the Medicare

beneficiary or a proxy respondent if the beneficiary is not able to respond. For survey participants who are living in a nursing home or another residential care facility, such as an assisted living residence, retirement home or a long-term care unit in a hospital or mental health facility, MCBS interviews are conducted with a staff member designated by the facility administrator as the most appropriate to answer the ques- tions. Data from the MCBS analysis that are included in 2017 Alzheimer’s Disease Facts and Figures pertain only to Medicare beneficiaries age 65 and older. For this MCBS analysis, people with dementia are defined as:

� Community-dwelling survey participants who answered yes to the MCBS question, “Has a doctor ever told you that you had Alzheimer’s disease or dementia?” Proxy responses to this question were accepted.

� Survey participants who were living in a nursing home or other residential care facility and had a diagnosis of Alzheimer’s disease or dementia in their medical record.

� Survey participants who had at least one Medicare claim with a diagnostic code for Alzheimer’s or other dementias in 2008. The claim could be for any Medicare service, including hospital, skilled nursing facility, outpatient medical care, home health care, hospice or physician, or other health care provider visit. The diagnostic codes used to identify survey participants with Alzheimer’s or other dementias are 331.0, 331.1, 331.11, 331.19, 331.2, 331.7, 331.82, 290.0, 290.1, 290.10, 290.11, 290.12, 290.13, 290.20, 290.21, 290.3, 290.40, 290.41, 290.42, 290.43, 291.2, 294.0, 294.1, 294.10 and 294.11.

Costs from the MCBS analysis are based on responses from 2011 and reported in 2016 dollars.

A24Differences in estimated costs reported by Hurd and colleagues: Hurd et al. [237] estimated per-person costs using data from participants in ADAMS, a cohort in which all individuals underwent diagnostic assessments for de- mentia. 2017 Alzheimer’s Disease Facts and Figures esti- mated per-person costs using data from the Medicare Current Beneficiary Survey (MCBS). One reason that the per-person costs estimated by Hurd et al. are lower than those reported in Facts and Figures is that ADAMS, with its diagnostic evaluations of everyone in the study, is more likely than MCBS to have identified individuals with less severe or undiagnosed Alzheimer’s. By contrast, the individuals with Alzheimer’s registered by MCBS are likely to be those with more severe, and therefore more costly, illness. A second reason is that Hurd et al.’s esti- mated costs reflect an effort to isolate the incremental costs associated with Alzheimer’s and other dementias (those costs attributed only to dementia), while the per- person costs in 2017 Alzheimer’s Disease Facts and Figures incorporate all costs of caring for people with the disease (regardless of whether the expenditure was related to dementia or a coexisting condition).

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