Assignment 1

Personality and Alzheimer’s Disease: An Integrative Review

Antonio Terracciano and Angelina R. Sutin Florida State University College of Medicine

The objective of this article is to review and integrate interrelated areas of research on personality and Alzheimer’s disease (AD). Prospective studies indicate that individuals who score higher on conscien- tiousness (more responsible and self-disciplined) and lower on neuroticism (less anxious and vulnerable to stress) have a reduced risk of developing dementia, even in the presence of AD neuropathology. Personality is also related to measures of cognitive performance and cognitive decline, with effect sizes similar to those of other clinical, lifestyle, and behavioral risk factors. These associations are unlikely to be due to reverse causality: Long-term prospective data indicate that there are no changes in personality that are an early sign of the disease during the preclinical phase of AD. With the onset and progression of dementia, however, there are large changes in personality that are reported consistently by caregivers in retrospective studies and are consistent with the clinical criteria for the diagnosis of dementia. The review also discusses potential mechanisms of the observed associations and emphasizes the need for prospective studies to elucidate the interplay of personality traits with AD neuropathology (amyloid and tau biomarkers) in modulating the risk and timing of onset of clinical dementia. The article concludes with the implications of personality research for identifying those at greater risk of AD and the potential of personality-tailored interventions aimed at the prevention and treatment of AD.

Keywords: personality, dementia, Alzheimer’s disease, cognitive decline

Alzheimer’s disease (AD) is the most common cause of demen- tia and the fastest-growing leading cause of death in the United States. AD is a progressive neurodegenerative disease that often manifests first as mild cognitive impairment (MCI) and then dementia. It is characterized by loss of memory and other cognitive functions and by changes in behavior, mood, and personality. These losses interfere with a person’s daily life and pose a signif- icant burden to families and the health care system. Besides AD, other types of dementia include Lewy body dementia, frontotem- poral dementia, and vascular dementia.

This article reviews and integrates the literature on personality as a risk factor for dementia, personality change in people with dementia, and potential pathways that may explain the observed associations. We further point to research questions that need to be addressed to advance knowledge on personality and dementia and consider the implications for the diagnosis and treatment of AD. Consistent with the literature on personality and dementia, this review focuses on research based on the five-factor model of personality.

Personality and Risk of Dementia and Cognitive Decline

Dementia Risk

Other than rare cases caused by specific genetic mutations, AD is a complex, multifactorial disease. Age is the strongest risk factor for AD, with increasing incidence from 1% to 2% for individuals aged 60 to 65 to about 30% for those over the age of 85. The e4 variant of the apolipoprotein E (APOE) gene is another strong risk factor. Other prominent risk factors can be grouped broadly under cardiovascular (e.g., midlife obesity, midlife hypertension, and diabetes), behavioral (e.g., smoking and physical inactivity), and psychosocial (depression, social contact, and education) risk (Bey- doun et al., 2014; Chuang et al., 2016; Whitmer, Sidney, Selby, Johnston, & Yaffe, 2005).

Personality traits have robust links with psychological, behav- ioral, and clinical risk factors for AD (Chapman, Roberts, & Duberstein, 2011; Hampson, 2012). For example, neuroticism is a strong risk factor for major depression (Kendler, Gatz, Gardner, & Pedersen, 2006) and conscientiousness is related to cigarette smok- ing, physical inactivity, and obesity (Sutin et al., 2016). Personality traits are also related to educational achievements, coping skills, and the quality and quantity of interpersonal relations, which in turn are associated with an increased vulnerability to dementia (Beydoun et al., 2014; Crooks, Lubben, Petitti, Little, & Chiu, 2008).

These links have led to the hypothesis that personality traits are associated with the risk of developing AD and related dementias. A recent meta-analysis (Terracciano et al., 2014) summarized the results of five prospective studies that included up to 5,054 individuals (Duberstein et al., 2011; Terracciano et al., 2014; Wilson et al., 2005; Wilson et al., 2006; Wilson, Schneider, Arnold, Bienias, & Bennett,

Antonio Terracciano, Department of Geriatrics, Florida State University College of Medicine; Angelina R. Sutin, Department of Behavioral Science and Social Medicine, Florida State University College of Medicine.

The authors’ work is supported by the National Institute on Aging of the National Institutes of Health Award R03AG051960 and R01AG053297. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Correspondence concerning this article should be addressed to Antonio Terracciano, Department of Geriatrics, Florida State University College of Medicine, 1115 West Call Street, Tallahassee, FL 32306. E-mail: antonio [email protected]

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Personality Disorders: Theory, Research, and Treatment © 2019 American Psychological Association 2019, Vol. 10, No. 1, 4 –12 1949-2715/19/$12.00 http://dx.doi.org/10.1037/per0000268

4

2007). At baseline, individuals free of cognitive impairment com- pleted a self-report version of the NEO Personality Inventory. These individuals were then followed over time to investigate whether personality traits predicted who developed clinical dementia. There was consistent evidence that individuals who scored higher on neu- roticism or lower on conscientiousness had a greater risk of incident AD. Although there was weak evidence for an association in the individual studies, the meta-analysis indicated that higher openness and agreeableness were associated with a slightly reduced risk of AD. Extraversion was unrelated to AD risk. The effects of neuroticism and conscientiousness were independent of each other and there was no interaction between the two traits (Terracciano et al., 2014; Wilson et al., 2005). Two studies examined the facets of neuroticism and found that anxiety and vulnerability to stress were significant predictors of incident AD (Terracciano et al., 2014; Wilson, Begeny, Boyle, Sch- neider, & Bennett, 2011). Two studies that examined the facets of conscientiousness found that several of them predicted incident de- mentia, with low self-discipline and responsibility being the strongest predictors (Sutin, Stephan, & Terracciano, 2017; Terracciano et al., 2014).

The effects of neuroticism and conscientiousness are not only consistent across studies but also of non-negligible magnitude. In the Religious Order Study (Wilson et al., 2007), for example, those scoring in the bottom 10% of conscientiousness had about double the risk of AD as compared with those in the top 10%. Similarly, in the Baltimore Longitudinal Study of Aging (Terracciano et al., 2014), individuals with scores in the top quartile of neuroticism or the lowest quartile of conscientiousness had a threefold increased risk of incident AD. These effect sizes are similar or larger than those found for cardiovascular and behavioral risk factors, such as diabetes, midlife obesity, midlife hypertension, lower education, physical inactivity, and cigarette smoking (Barnes & Yaffe, 2011; Daviglus et al., 2011).

Cognitive Performance, Decline, and Impairment

Consistent with prospective studies that examined incident AD, personality traits are associated with cognitive decline and mild impairments that can culminate in dementia. A large study of 4,039 members of the Swedish Twin Registry found neuroticism, but not extraversion, to be associated with cognitive impairment status 25 years later (Crowe, Andel, Pedersen, Fratiglioni, & Gatz, 2006). In cognitively healthy older adults, personality traits have been associated with the level of cognitive performance and rate of cognitive decline (Caselli et al., 2016). For example, in the Health and Retirement Study (N � 13,987), individuals who scored lower on neuroticism or higher on openness and conscientiousness per- formed better on a memory task (Luchetti, Terracciano, Stephan, & Sutin, 2016). A meta-analysis indicated that higher neuroticism and lower conscientiousness were associated with steeper cogni- tive decline over time. Although the association between person- ality and cognitive decline over short follow-up periods was small, the effects were stronger than the effects of cardiovascular condi- tions, physical inactivity, and history of smoking and psycholog- ical distress (Luchetti et al., 2016). The protective effects of high conscientiousness are particularly strong in predicting the rate of cognitive decline within the last three years before death compared with the preterminal decline (Wilson et al., 2015). Finally, person- ality is also associated with subjective cognition. Individuals who

score higher on neuroticism or lower on conscientiousness report more cognitive complaints (Steinberg et al., 2013) and worse self-rated memory (Luchetti et al., 2016). Subjective cognitive complaints are associated with an increased risk of incident AD (Geerlings, Jonker, Bouter, Adèr, & Schmand, 2014).

Personality Disorder

In addition to normal personality traits, personality disorders have also been associated with dementia. Most of this evidence is from studies with retrospective assessments by family members. Obsessive– compulsive personality disorder, for example, is asso- ciated with an increased risk of AD (Dondu, Sevincoka, Akyol, & Tataroglu, 2015); other studies report associations with almost all personality disorders (Nicholas et al., 2010).

Pathways Linking Personality to Dementia

Mechanisms

As mentioned previously, personality traits are related to mul- tiple lifestyles and health factors that increase risk of dementia, and these factors are potential behavioral and clinical mechanisms through which personality is associated with dementia risk. In particular, personality may contribute to risk of dementia by shap- ing over the lifetime an individual’s reactions to stress, health behaviors, and engagement in physical, cognitive, and social ac- tivities. The finding that personality is associated with inflamma- tory markers (Luchetti, Barkley, Stephan, Terracciano, & Sutin, 2014) and the brain-derived neurotrophic factor (Terracciano et al., 2011) suggests potential biological pathways. Still other studies have tested to what extent the association between personality and incident AD or cognitive decline was accounted for by other risk factors such as education, APOE genotype, activity patterns, or vascular conditions. Although attenuated, the associations between personality and cognition-related outcomes generally remained significant when accounting for such factors (Luchetti et al., 2016; Sutin et al., 2017; Terracciano, Stephan, Luchetti, Albanese, & Sutin, 2017; Wilson et al., 2003; Wilson et al., 2007). Some studies control for measures of distress or depressive symptoms when examining neuroticism as a predictor of incident AD (Johansson et al., 2014), but these findings are difficult to interpret given the conceptual and measurement overlap between neuroticism and other measures of distress. Rather than confounding factors, the psychological, behavioral, and clinical variables are likely to be partial mediators, and thus mechanisms, of the association between personality and incident AD.

Moderators

A few studies have tested whether personality interacts with other risk factors to modulate the effect of personality on cognitive outcomes. Neuroticism, for example, may moderate the effect of the APOE genotype on cognitive function and risk of dementia (Dar-Nimrod et al., 2012). Other studies, however, found different (Sapkota, Wiebe, Small, & Dixon, 2016) or no interactions (Ter- racciano et al., 2014). Personality may also interact with the environment to predict dementia risk (e.g., inactive or socially isolated lifestyle; Wang et al., 2009), but to date, there is no robust

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5PERSONALITY AND ALZHEIMER’S DISEASE

evidence that the associations vary across demographic groups defined by age, sex, race, ethnicity, or education (Terracciano, Stephan, Luchetti, Albanese, et al., 2017).

Reverse Causality

Behavioral and personality changes are a common clinical sign of AD (McKhann et al., 2011), and changes in the preclinical phase could be responsible for the observed associations between personality and incident dementia. This reverse causality hypoth- esis is plausible because the neuropathological change in AD occurs years before dementia onset (Jack et al., 2013). The accu- mulation of amyloid-� (A�) and tau leads to neuronal dysfunction and cell death, which spreads through the brain and is manifested in the clinical symptoms. Cerebrospinal fluid (CSF) and positron emission tomography (PET) amyloid imaging indicate that A� accumulation occurs about a decade or more before clinical man- ifestation of the disease (Buchhave et al., 2012; Resnick et al., 2015). Although there is a delay in the onset of cognitive impair- ment, it is possible that personality change occurs earlier. For example, individuals who later developed AD were cognitively normal but may have some A� deposition at the time they com- pleted the personality questionnaire. The cascading neurodegen- eration may have an impact on their brain and potentially their personality before the onset of cognitive symptoms. Of note, many studies on personality and incident AD were based on cohorts of older adults (Mage � 70 years) and had relatively short follow-up periods (�6 years). As such, those who developed dementia dur- ing the follow-up period were likely in the AD prodromal phase when the personality questionnaire was completed.

Although plausible, there is clear evidence against the reverse causality hypothesis. A recent long-term prospective study (n � 2,046) examined repeated NEO Personality Inventory over a time span of up to 36 years (Terracciano, An, Sutin, Thambisetty, & Resnick, 2017a). It found that the personality trajectories of those who developed AD were not significantly different from those who re- mained cognitively normal. Even within the last few years before the onset of MCI or dementia, the study found no evidence of preclinical changes in personality that could be interpreted as an early sign of AD (but see, Balsis, Carpenter, & Storandt, 2005; Duchek, Balota, Storandt, & Larsen, 2007). Other evidence against the reverse cau- sality hypothesis includes findings that personality is associated with cognitive performance and predicts cognitive decline in relatively young samples (e.g., Mage � 45 years in Hock et al., 2014).

Personality Resilience in the Presence of AD Neuropathology

As noted above, A� dysregulation occurs years before the onset of dementia, and 20% to 40% of clinically normal older adults have biomarker evidence of AD neuropathology (Jack et al., 2013; Sperling et al., 2011). There is also considerable variability in the time lag between the emergence of AD neuropathology (e.g., positive PET amyloid imaging) and the onset of clinical dementia. Consistent with biomarker evidence, about 30% of individuals without cognitive impairment before death are found to meet the neuropathological criteria of AD at autopsy (Balsis et al., 2005; Driscoll & Troncoso, 2011). Personality traits may moderate the emergence of clinical signs of dementia in individuals with AD

pathophysiology. We tested this hypothesis by comparing the personality traits of those who developed dementia with those who did not despite being found at autopsy to meet criteria for AD neuropathology. Compared with those with clinical dementia, asymptomatic individuals (those with AD neuropathology but no clinical dementia) scored higher on conscientiousness and lower on neuroticism (Terracciano et al., 2013). These findings suggest that a resilient personality profile plays a significant role at the interface of neuropathological processes and the manifestation of clinical symptoms. In people with underlying AD neurodegenera- tion, personality traits may help postpone the onset of clinical signs. Research with in vivo biomarkers (CSF or imaging) and concurrent personality assessments in large prospective studies is needed to confirm this hypothesis. Such research would also help clarify the temporal progression of personality change that occurs with the onset of other clinical signs and the evolution of AD biomarkers.

The evidence is mixed on the link between personality traits and neuropathology at autopsy. Higher neuroticism has been associ- ated with more advanced spread of neurofibrillary tangles in limbic and neocortical regions, as indexed by Braak staging, but not with levels of A� plaques (Terracciano et al., 2013); other studies have found no association with neuropathology at autopsy (Wilson et al., 2003; 2007). Data from in vivo brain imaging indicate that individuals with MCI who score higher on neuroti- cism or lower on conscientiousness have more severe white matter lesions but not cerebrovascular lesions or medial temporal lobe atrophy (Duron et al., 2014). In a large community-based cohort of about 500 older adults, individuals who scored lower on consci- entiousness had more white matter hyperintensities, white matter fractional anisotropy, and brain-tissue loss (Booth et al., 2014).

Personality Changes and Dementia

Since Alois Alzheimer’s first case, personality change has been observed in individuals with AD and related dementias (Hippius & Neundörfer, 2003). Current National Institute on Aging and Alz- heimer’s Association diagnostic guidelines indicate that the diag- nosis of dementia requires impairment in at least two of five domains; one of the five domains is personality change, such as impaired motivation, social withdrawal, and increased irritability (McKhann et al., 2011).

Retrospective Studies

The common clinical observations and dementia guidelines are supported by research based on standardized measures of person- ality (Robins Wahlin & Byrne, 2011). Family members (usually a spouse or adult child) are asked to rate the premorbid (before the onset of dementia) and current personality of the individual with dementia. Good rater agreement is found when multiple infor- mants are used (Strauss, Pasupathi, & Chatterjee, 1993), and current ratings are reliable and sensitive to change when repeated over time (Strauss & Pasupathi, 1994). Most studies have shown remarkably consistent patterns in terms of direction and magnitude of change. As illustrated in Figure 1, which is based on data from a meta-analysis of nine studies (Robins Wahlin & Byrne, 2011), the differences between the premorbid and current ratings point to large changes in neuroticism (about a 1.4-SD increase), extraver-

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6 TERRACCIANO AND SUTIN

sion (about a 1.3-SD decrease), and conscientiousness (about a 2.4-SD decrease). Smaller declines are also observed for openness and agreeableness (�0.5 SD). The differences in neuroticism, extraversion, and conscientiousness are large in absolute terms and are more than 10-fold larger than the changes typically observed with normal aging (Terracciano, McCrae, Brant, & Costa, 2005). It is worth noting that these studies compare premorbid with current personality. As such, the observed changes may have occurred after the onset of dementia, especially because prospec- tive research has found no changes in the preclinical phase. Similar patterns of personality change have been observed in individuals with MCI (Donati et al., 2013), but the magnitude was consider- ably smaller (about 0.25 SD). Given the evidence to date, the changes in personality may start with MCI and become larger with the onset and progression of dementia.

By the time of diagnosis, observer ratings of personality can discriminate healthy aging from early-stage AD beyond the per- formance on standard neuropsychological testing (Duchek et al., 2007). Personality change may also help differentiate AD from other types of dementia, such as frontotemporal dementia and Lewy body dementia, to improve differential diagnosis. However, the small studies that compared personality change across different types of dementia have found mixed results (Lykou et al., 2013; Torrente et al., 2014).

Prospective Studies

Compared with the dozen studies that examined personality change with a retrospective study design, fewer studies have used a prospective design to investigate personality change. As de- scribed previously, a long-term longitudinal study found no evi- dence of significant personality change in the preclinical phase of AD (Terracciano, An, et al., 2017a). Similarly, a German longitu- dinal study (Kuzma, Sattler, Toro, Schonknecht, & Schroder, 2011) obtained self-reported personality ratings of 222 older adults three times over 12 years. At baseline, the participants were not cognitively impaired, but 66 were found to have developed MCI by the third follow-up. Contrary to expectation and a retrospective study (Donati et al., 2013), the group that developed MCI declined

slightly on neuroticism, showed no change on extraversion (as compared with controls), and showed no change on conscientious- ness (in the article, mean conscientiousness at t3 was mistyped as 2.3 instead of 3; Personal communication, October 2015). One prospective study found change in self-reported neuroticism but not extraversion in 86 octogenarians who received a diagnosis of dementia (Yoneda, Rush, Berg, Johansson, & Piccinin, 2016). Given that this latter study included the assessment at the time of the diagnosis, the increase in neuroticism is likely to have occurred at the time of the diagnosis. One prospective study over 4 years found that extraversion declined as the Clinical Dementia Rating progressed from 0.5 (very mild) to �2 (moderate to severe disease stage; Sollberger et al., 2011). Taken together, evidence from studies with a prospective design and the use of self-report data finds no evidence of change in the preclinical phase of the disease, whereas changes become evident at the time of the onset of dementia.

Self-Reports Versus Observer Ratings

In nonclinical samples, there is generally a moderate agreement between self-ratings and observer ratings (Funder, 1995). How- ever, there is a discrepancy between the personality-as-a-risk- factor literature that is based on self-reports (Terracciano et al., 2014) and the personality-change literature that relies on observer ratings (Robins Wahlin & Byrne, 2011). The former indicates that people who later develop AD tend to score themselves as higher on neuroticism and lower on conscientiousness before the onset of dementia. By contrast, informants rate the premorbid neuroticism and conscientiousness in the normal range (see Figure 1), which suggests that informants provide overly positive retrospective judgments. A contrast has also been found in studies that directly compared observer ratings with self-reports by individuals with mild dementia. For example, Richman (1989) found that nursing home residents with mild dementia rated themselves as less neu- rotic and more extraverted, open, agreeable, and conscientious compared with how their family members rated them. Similar findings were obtained in at least two other studies, and in each case, the difference between the groups with dementia and controls

Figure 1. Personality change in individuals with dementia from nine studies summarized by Robins Wahlin and Byrne (2011). See the online article for the color version of this figure.

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7PERSONALITY AND ALZHEIMER’S DISEASE

was smaller when relying on self-reports as compared with ob- server ratings (Duchek et al., 2007; Pocnet, Rossier, Antonietti, & von Gunten, 2011).

Although self-reports in individuals with advanced dementia are difficult to obtain and of dubious reliability, the ratings of indi- viduals with early-stage dementia cannot be dismissed as unreli- able. High retest correlations (range of rtt � .76 for agreeableness to rtt � .95 for neuroticism) over 1 to 2 weeks support the reliability of self-reports in individuals with mild dementia (Richman, 1989). In- ternal consistency also remains relatively high among people with dementia (Terracciano, Stephan, Luchetti, & Sutin, 2017). The dis- crepancy between self-report and observer-report methods has been generally interpreted as impaired self-awareness (anosognosia) of ongoing personality change in individuals with MCI or dementia (Donati et al., 2013; Pocnet et al., 2011). For example, Rankin, Baldwin, Pace-Savitsky, Kramer, and Miller (2005) argued that indi- viduals with dementia (especially frontotemporal dementia) may lose the ability to update their self-image. The affected persons may respond to personality questionnaires by retrieving information rele- vant to their former self more than reflecting on their current person- ality. Of note, if changes in personality are not registered in self- reports, the association between self-report personality and incident dementia cannot be due to changes in the traits, as would be predicted by the reverse causality hypothesis.

A number of other motives and biases may contribute to the discrepancies between self-report and informant-report methods. Although reliable across time and raters (Strauss & Pasupathi, 1994; Strauss et al., 1993), systematic biases cannot be ruled out with the observer rating method, such as recall biases, hindsight bias, idealization of the person before the disease, and contrast effects when comparing premorbid with current personality. Cur- rent ratings are potentially influenced by the diagnosis or the labeling of dementia. In cases of uncertainty or lack of informa- tion, knowledge about the disease or stereotypes could influence observer ratings (Hoerger et al., 2011). Long-term prospective studies with repeated assessments of both self-ratings and observer ratings are needed to tease apart these possibilities and determine at what stage of the disease process, the two methods of person- ality assessment start to diverge. Such research would be most informative if the changes in personality can be mapped against changes in the underlying neuropathology (e.g., CSF or PET biomarkers) and other clinical signs.

Rank Order Stability

In addition to mean-level trajectories, the rank order stability of personality provides information on whether individual differences are maintained with the progression of the neurodegenerative disease. A prospective study that examined self-report personality found the stability of all five traits to be substantially lower in the group with dementia compared with unimpaired old adults: the 4-year stability coefficient averaged across the five traits was .43 in the dementia group and about .70 in older adults with no dementia (Terracciano, Stephan, Luchetti, & Sutin, 2017). In ret- rospective studies with observer ratings, a few studies reported correlations ranging from .3 to .8 between the premorbid and current personality traits of individuals with mild to moderate dementia (see Terracciano, Stephan, Luchetti, & Sutin, 2017). These coefficients suggest that although personality becomes less

stable, individuals with dementia retain some of their personality characteristics, at least in the mild to moderate stages of dementia. The persistence of some aspects of personality is of relevance for dementia care and underscores the continuity of personhood be- yond the onset of dementia; personality can provide a framework to understand the behaviors, preferences, and values of the person with dementia.

Implications of Personality for Diagnosis and Interventions

Diagnostic Utility

Early diagnosis is crucial for the care of patients. There is also growing awareness that interventions need to occur before the disease progresses to advanced stages. It is therefore essential to identify AD cases at the preclinical stage of the disease, when disease-modifying interventions may be most effective (Sperling et al., 2011). Research on early markers of AD has focused on neuropathology, but A� and other biomarkers are only moderately correlated with clinical dementia (Holmes et al., 2008). In combi- nation with biomarkers, personality traits may help identify indi- viduals at a greater risk of developing clinical dementia (Terrac- ciano et al., 2013) and aid in the early diagnosis of AD (Duchek et al., 2007; Smith-Gamble et al., 2002). With the disease progres- sion, personality provides a framework to interpret behavioral and psychological symptoms (Sutin, Stephan, Luchetti, & Terracciano, 2017).

Clinical Trials

High neuroticism and low conscientiousness are the two traits most associated with cognitive decline and risk of dementia. Yet, individuals with these traits are less likely to volunteer for research studies (Lönnqvist et al., 2007). It is thus critical to consider personality traits in selection criteria for clinical trials, to select the individuals with the most vulnerable personality profile who are in the greatest need of effective treatments. As suggested by others (Duberstein et al., 2011), tailored incentives could improve recruit- ment of the population with personality-related vulnerability.

Intervention-Driven Personality Change

Estimates of population attributable risk suggest that neuroti- cism and conscientiousness may each account for about 10% of AD cases (Terracciano et al., 2014). Personality traits could thus be a promising target of interventions aimed at preventing or reducing the burden of AD. Interventions aimed at changing mal- adaptive aspects of personality are particularly enticing because these traits are thought to be distal causes of the disease and are linked to other risk factors and life outcomes. In addition to potential direct benefits, reducing neuroticism and increasing con- scientiousness could have the added benefit of potentially reducing other risk factors, such as physical inactivity, social isolation, cigarette smoking, midlife obesity, and other cardiovascular risk factors. Despite the potential direct and indirect benefits, relatively little is known about the effects of interventions on personality.

Perhaps the best evidence for intervention-induced personality change comes from pharmacological and psychoeducational treat-

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8 TERRACCIANO AND SUTIN

ments. For example, for individuals with major depression, anti- depressants reduce the level of neuroticism (Costa, Bagby, Herbst, & McCrae, 2005; Tang et al., 2009). However, the side effects of psychotropic medications (e.g., benzodiazepines) in older adults can be particularly severe (Campanelli & The American Geriatrics Society 2012 Beers Criteria Update Expert Panel, 2012) and may aggravate more than reduce the risk of dementia (de Gage et al., 2012; Rosenberg et al., 2012). Besides pharmacological interven- tions, there is a vast literature on the benefits of cognitive– behavioral treatments for anxiety and depression, which are likely to have an impact on neuroticism and other personality traits (see also Roberts et al., this issue). In the area of addiction, an outpa- tient 6-week drug rehabilitation program study found significant changes (d � 0.3) in neuroticism, agreeableness, and conscien- tiousness that were maintained over a 15-month follow-up (Pied- mont, 2001). There is also increasing interest in cognitive training for personality change, but a recent study found that an intensive cognitive training for memory and perceptual speed had no posi- tive impact on personality (Sander, Schmiedek, Brose, Wagner, & Specht, 2017). This finding might not be surprising, given that cognitive training generally has limited transfer to other domains beyond the trained tasks. Interventions aimed at increasing phys- ical activity (e.g., yoga, dancing) may have potential benefits for personality in addition to direct benefits for physical and cognitive health. In an observational study, older adults who were more physically active had a more favorable pattern of personality change (Stephan, Sutin, & Terracciano, 2014). However, it re- mains to be tested whether treatments designed to improve cogni- tion, fitness, or other domains have broader and lasting benefits on personality.

Changing Personality

Although informative, pharmacological and psychoeducational interventions were done to treat depression and addiction or to slow down cognitive decline. In contrast, a recent study was designed specifically to change personality (Hudson & Fraley, 2015). In the first 16-week experiment, however, the intervention back-fired, that is, those randomly assigned to a goal-setting in- tervention increased in neuroticism and decreased in agreeableness and conscientiousness. A second intervention based on more spe- cific and concrete “change plans” was associated with better outcomes for neuroticism and conscientiousness but not for agree- ableness (it decreased). Despite including college students, the study had high attrition (�72%), which suggests that even among students, there are significant barriers to consider, especially for those low on conscientiousness. The mixed results should not discourage further research. The bottom-up approach to changing behaviors and, over time, personality traits has been advocated by others (Magidson, Roberts, Collado-Rodriguez, & Lejuez, 2014) and deserves further scrutiny. Such interventions are consistent with the individual’s desire to change (Hudson & Fraley, 2015) and the parental, school, workplace, friend, religious, institutional, and social pressures to change problematic behaviors and traits. Interventions can thus rely on tools that have been developed to address specific problems (e.g., smoking cessation) and test which tools might have an impact on personality over time. Furthermore, future research should examine whether observed effects in stu- dent samples can be replicated in adult samples, corroborated by

observer ratings, and maintained over time. Interventions should be informed by evidence that personality is more malleable in children and adolescents, and it becomes increasingly stable in younger and especially in middle and older ages. Even after decades, stability coefficients are about rtt � .7 among adults older than 30 years (Terracciano, Costa, & McCrae, 2006). Such evi- dence suggests that interventions early in life might be more efficacious. Perhaps, the most important and challenging question is whether experimentally induced alterations in self-reported per- sonality traits have the desired effect on behavior change (e.g., more physical activity, quitting smoking) and health outcomes (English & Carstensen, 2014).

Personality-Tailored Interventions

In the era of precision medicine (leveraging genetic and other information to enhance personalized interventions) and person- centered care (Edvardsson, Winblad, & Sandman, 2008), consid- ering personality traits may be crucial for many aspects of demen- tia care. Most interventions tend to follow a “one-size-fits-all” approach that ignores individual differences. There is growing interest in models of care that recognize and respect the individ- ual’s unique preferences, values, interests, and needs. Recognition of personality differences and other basic psychological disposi- tions is likely to shift the focus from the disease to the person and to produce more effective interventions. For example, an interven- tion for risk reduction of alcohol misuse has shown that personality-targeted prevention programs are feasible and effective (Conrod et al., 2013). Similarly, personality-targeted interventions were effective in reducing depressive, anxiety, and conduct symp- toms in high-risk youth (O’Leary-Barrett et al., 2013). Whether such personality-targeted interventions are more cost-effective than standard approaches remains to be determined. In dementia care, interventions that fit activities to individual preferences have been found to be more effective in reducing agitation and other behavioral symptoms (Gitlin et al., 2008; Kolanowski, Litaker, Buettner, Moeller, & Costa, 2011). In evaluating tailored interven- tions, more research is needed to examine whether the five broad factors or specific facets provide the most useful information for treatment. It is also important to include personality measures in large trials to test personality traits as predictors of treatment adherence and heterogeneity of treatment effects. This would provide an evidence base on which interventions fit best, given the psychological disposition of the person. Such knowledge would empower clinicians to provide care that is more person-centered.

Conclusion

We reviewed evidence that conscientiousness and other person- ality traits may reduce risk of clinical dementia. We discussed several potential mechanisms for this protective role of personal- ity, including indirect pathways by reducing other risk factors (e.g., physical inactivity, depression) and direct pathways by fa- voring brain health (Booth et al., 2014; Terracciano et al., 2011). In particular, we reviewed evidence that in the presence of AD neuropathology, personality may forestall the manifestation of clinical dementia. And contrary to the reverse causality hypothesis, long-term prospective data indicate that there are no preclinical changes in personality that may explain the association. We inte-

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9PERSONALITY AND ALZHEIMER’S DISEASE

grated these findings with evidence that dementia has an impact on personality, which constitutes a core clinical sign that emerges with the onset of dementia. We also point to the need for more prospective studies that include AD biomarkers, particularly to examine how personality modulates timing of disease onset. In conclusion, personality traits are a promising tool for the diagno- sis, prevention, and treatment of dementia.

References

Balsis, S., Carpenter, B. D., & Storandt, M. (2005). Personality change precedes clinical diagnosis of dementia of the Alzheimer type. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 60, 98 –101. http://dx.doi.org/10.1093/geronb/60.2.P98

Barnes, D. E., & Yaffe, K. (2011). The projected effect of risk factor reduction on Alzheimer’s disease prevalence. The Lancet Neurology, 10, 819 – 828. http://dx.doi.org/10.1016/S1474-4422(11)70072-2

Beydoun, M. A., Beydoun, H. A., Gamaldo, A. A., Teel, A., Zonderman, A. B., & Wang, Y. (2014). Epidemiologic studies of modifiable factors associated with cognition and dementia: Systematic review and meta- analysis. BMC Public Health, 14, 643. http://dx.doi.org/10.1186/1471- 2458-14-643

Booth, T., Mõttus, R., Corley, J., Gow, A. J., Henderson, R. D., Maniega, S. M., . . . Deary, I. J. (2014). Personality, health, and brain integrity: The Lothian Birth Cohort Study 1936. Health Psychology, 33, 1477– 1486. http://dx.doi.org/10.1037/hea0000012

Buchhave, P., Minthon, L., Zetterberg, H., Wallin, A. K., Blennow, K., & Hansson, O. (2012). Cerebrospinal fluid levels of �-amyloid 1– 42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Archives of General Psychiatry, 69, 98 –106. http:// dx.doi.org/10.1001/archgenpsychiatry.2011.155

Campanelli, C. M., & The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. (2012). American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 60, 616 – 631. http:// dx.doi.org/10.1111/j.1532-5415.2012.03923.x

Caselli, R. J., Dueck, A. C., Locke, D. E., Henslin, B. R., Johnson, T. A., Woodruff, B. K., . . . Geda, Y. E. (2016). Impact of personality on cognitive aging: A prospective cohort study. Journal of the International Neuropsychological Society, 22, 765–776. http://dx.doi.org/10.1017/ S1355617716000527

Chapman, B. P., Roberts, B., & Duberstein, P. (2011). Personality and longevity: Knowns, unknowns, and implications for public health and personalized medicine. Journal of Aging Research, 2011, Article ID 759170. http://dx.doi.org/10.4061/2011/759170

Chuang, Y. F., An, Y., Bilgel, M., Wong, D. F., Troncoso, J. C., O’Brien, R. J., . . . Thambisetty, M. (2016). Midlife adiposity predicts earlier onset of Alzheimer’s dementia, neuropathology and presymptomatic cerebral amyloid accumulation. Molecular Psychiatry, 21, 910 –915. http://dx.doi .org/10.1038/mp.2015.129

Conrod, P. J., O’Leary-Barrett, M., Newton, N., Topper, L., Castellanos- Ryan, N., Mackie, C., & Girard, A. (2013). Effectiveness of a selective, personality-targeted prevention program for adolescent alcohol use and misuse: A cluster randomized controlled trial. Journal of the American Medical Association Psychiatry, 70, 334 –342. http://dx.doi.org/10.1001/ jamapsychiatry.2013.651

Costa, P. T., Jr., Bagby, R. M., Herbst, J. H., & McCrae, R. R. (2005). Personality self-reports are concurrently reliable and valid during acute depressive episodes. Journal of Affective Disorders, 89, 45–55. http:// dx.doi.org/10.1016/j.jad.2005.06.010

Crooks, V. C., Lubben, J., Petitti, D. B., Little, D., & Chiu, V. (2008). Social network, cognitive function, and dementia incidence among el- derly women. American Journal of Public Health, 98, 1221–1227. http://dx.doi.org/10.2105/AJPH.2007.115923

Crowe, M., Andel, R., Pedersen, N. L., Fratiglioni, L., & Gatz, M. (2006). Personality and risk of cognitive impairment 25 years later. Psychology and Aging, 21, 573–580. http://dx.doi.org/10.1037/0882-7974.21.3.573

Dar-Nimrod, I., Chapman, B. P., Franks, P., Robbins, J., Porsteinsson, A., Mapstone, M., & Duberstein, P. R. (2012). Personality factors moderate the associations between apolipoprotein genotype and cognitive function as well as late onset Alzheimer disease. The American Journal of Geriatric Psychiatry, 20, 1026 –1035. http://dx.doi.org/10.1097/JGP .0b013e318267016b

Daviglus, M. L., Plassman, B. L., Pirzada, A., Bell, C. C., Bowen, P. E., Burke, J. R., . . . Williams, J. W., Jr. (2011). Risk factors and preventive interven- tions for Alzheimer disease: State of the science. Archives of Neurology, 68, 1185–1190. http://dx.doi.org/10.1001/archneurol.2011.100

de Gage, S. B., Bégaud, B., Bazin, F., Verdoux, H., Dartigues, J.-F., Pérès, K., . . . Pariente, A. (2012). Benzodiazepine use and risk of dementia: Prospective population based study. British Medical Journal, 345, e6231. http://dx.doi.org/10.1136/bmj.i90

Donati, A., Studer, J., Petrillo, S., Pocnet, C., Popp, J., Rossier, J., & von Gunten, A. (2013). The evolution of personality in patients with mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 36, 329 –339. http://dx.doi.org/10.1159/000353895

Dondu, A., Sevincoka, L., Akyol, A., & Tataroglu, C. (2015). Is obsessive– compulsive symptomatology a risk factor for Alzheimer-type dementia? Psychiatry Research, 225, 381–386. http://dx.doi.org/10.1016/j.psychres .2014.12.010

Driscoll, I., & Troncoso, J. (2011). Asymptomatic Alzheimer’s disease: A prodrome or a state of resilience? Current Alzheimer Research, 8, 330 –335. http://dx.doi.org/10.2174/156720511795745348

Duberstein, P. R., Chapman, B. P., Tindle, H. A., Sink, K. M., Bamonti, P., Robbins, J., . . . Franks, P. (2011). Personality and risk for Alzheimer’s disease in adults 72 years of age and older: A 6-year follow-up. Psy- chology and Aging, 26, 351–362. http://dx.doi.org/10.1037/a00213777

Duchek, J. M., Balota, D. A., Storandt, M., & Larsen, R. (2007). The power of personality in discriminating between healthy aging and early-stage Alzheimer’s disease. Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 62, 353–361. http://dx.doi.org/10.1093/ geronb/62.6.P353

Duron, E., Vidal, J. S., Bounatiro, S., Ben Ahmed, S., Seux, M. L., Rigaud, A. S., . . . Martel, G. (2014). Relationships between personality traits, medial temporal lobe atrophy, and white matter lesion in subjects suffering from mild cognitive impairment. Frontiers in Aging Neurosci- ence, 6, 195. http://dx.doi.org/10.3389/fnagi.2014.00195

Edvardsson, D., Winblad, B., & Sandman, P. O. (2008). Person-centred care of people with severe Alzheimer’s disease: Current status and ways forward. Lancet Neurology, 7, 362–367. http://dx.doi.org/10.1016/S1474- 4422(08)70063-2

English, T., & Carstensen, L. L. (2014). Will interventions targeting conscientiousness improve aging outcomes? Developmental Psychol- ogy, 50, 1478 –1481. http://dx.doi.org/10.1037/a0036073

Funder, D. C. (1995). On the accuracy of personality judgment: A realistic approach. Psychological Review, 102, 652– 670. http://dx.doi.org/10 .1037/0033-295X.102.4.652

Geerlings, M. I., Jonker, C., Bouter, L. M., Adèr, H. J., & Schmand, B. (2014). Association between memory complaints and incident Alzhei- mer’s disease in elderly people with normal baseline cognition. The American Journal of Psychiatry, 156, 531–537.

Gitlin, L. N., Winter, L., Burke, J., Chernett, N., Dennis, M. P., & Hauck, W. W. (2008). Tailored activities to manage neuropsychiatric behaviors in persons with dementia and reduce caregiver burden: A randomized pilot study. The American Journal of Geriatric Psychiatry, 16, 229 –239. http://dx.doi.org/10.1097/01.JGP.0000300629.35408.94

Hampson, S. E. (2012). Personality processes: Mechanisms by which personality traits “get outside the skin.” Annual Review of Psychology, 63, 315–339. http://dx.doi.org/10.1146/annurev-psych-120710-100419

T hi

s do

cu m

en t

is co

py ri

gh te

d by

th e

A m

er ic

an P

sy ch

ol og

ic al

A ss

oc ia

ti on

or on

e of

it s

al li

ed pu

bl is

he rs

. T

hi s

ar ti

cl e

is in

te nd

ed so

le ly

fo r

th e

pe rs

on al

us e

of th

e in

di vi

du al

us er

an d

is no

t to

be di

ss em

in at

ed br

oa dl

y.

10 TERRACCIANO AND SUTIN

Hippius, H., & Neundörfer, G. (2003). The discovery of Alzheimer’s disease. Dialogues in Clinical Neuroscience, 5, 101–108.

Hock, R. S., Lee, H. B., Bienvenu, O. J., Nestadt, G., Samuels, J. F., Parisi, J. M., . . . Spira, A. P. (2014). Personality and cognitive decline in the Baltimore Epidemiologic Catchment Area follow-up study. The Ameri- can Journal of Geriatric Psychiatry, 22, 917–925. http://dx.doi.org/10 .1016/j.jagp.2012.12.217

Hoerger, M., Chapman, B., Ma, Y., Tu, X., Useda, J. D., Hirsch, J., & Duberstein, P. (2011). Agreement between informant and self-reported personality in depressed older adults: What are the roles of medical illness and cognitive function? Psychology and Aging, 26, 1000 –1006. http://dx.doi.org/10.1037/a0023213

Holmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., . . . Nicoll, J. A. (2008). Long-term effects of Abeta42 immunisation in Alzheimer’s disease: Follow-up of a randomised, placebo-controlled phase I trial. The Lancet, 372, 216 –223. http://dx.doi.org/10.1016/S0140- 6736(08)61075-2

Hudson, N. W., & Fraley, R. C. (2015). Volitional personality trait change: Can people choose to change their personality traits? Journal of Per- sonality and Social Psychology, 109, 490 –507. http://dx.doi.org/10 .1037/pspp0000021

Jack, C. R., Jr., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., . . . Trojanowski, J. Q. (2013). Tracking patho- physiological processes in Alzheimer’s disease: An updated hypothetical model of dynamic biomarkers. The Lancet Neurology, 12, 207–216. http://dx.doi.org/10.1016/S1474-4422(12)70291-0

Johansson, L., Guo, X., Duberstein, P. R., Hällström, T., Waern, M., Ostling, S., & Skoog, I. (2014). Midlife personality and risk of Alzhei- mer disease and distress: A 38-year follow-up. Neurology, 83, 1538 – 1544. http://dx.doi.org/10.1212/WNL.0000000000000907

Kendler, K. S., Gatz, M., Gardner, C. O., & Pedersen, N. L. (2006). Personality and major depression: A Swedish longitudinal, population- based twin study. Archives of General Psychiatry, 63, 1113–1120. http://dx.doi.org/10.1001/archpsyc.63.10.1113

Kolanowski, A., Litaker, M., Buettner, L., Moeller, J., & Costa, P. T., Jr. (2011). A randomized clinical trial of theory-based activities for the behavioral symptoms of dementia in nursing home residents. Journal of the American Geriatrics Society, 59, 1032–1041. http://dx.doi.org/10 .1111/j.1532-5415.2011.03449.x

Kuzma, E., Sattler, C., Toro, P., Schonknecht, P., & Schroder, J. (2011). Premorbid personality traits and their course in mild cognitive impair- ment: Results from a prospective population-based study in Germany. Dementia and Geriatric Cognitive Disorders, 32, 171–177. http://dx.doi .org/10.1159/000332082

Lönnqvist, J. E., Paunonen, S., Verkasalo, M., Leikas, S., Tuulio- Henriksson, A., & Lönnqvist, J. (2007). Personality characteristics of research volunteers. European Journal of Personality, 21, 1017–1030. http://dx.doi.org/10.1002/per.655

Luchetti, M., Barkley, J. M., Stephan, Y., Terracciano, A., & Sutin, A. R. (2014). Five-factor model personality traits and inflammatory markers: New data and a meta-analysis. Psychoneuroendocrinology, 50, 181–193. http://dx.doi.org/10.1016/j.psyneuen.2014.08.014

Luchetti, M., Terracciano, A., Stephan, Y., & Sutin, A. R. (2016). Person- ality and cognitive decline in older adults: Data from a longitudinal sample and meta-analysis. The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 71, 591– 601. http://dx.doi .org/10.1093/geronb/gbu184

Lykou, E., Rankin, K. P., Chatziantoniou, L., Boulas, C., Papatriantafyllou, O., Tsaousis, I., . . . Papatriantafyllou, J. D. (2013). Big 5 personality changes in Greek bvFTD, AD, and MCI patients. Alzheimer Disease and Associated Disorders, 27, 258 –264. http://dx.doi.org/10.1097/WAD .0b013e31826e5504

Magidson, J. F., Roberts, B. W., Collado-Rodriguez, A., & Lejuez, C. W. (2014). Theory-driven intervention for changing personality: Expectancy

value theory, behavioral activation, and conscientiousness. Developmental Psychology, 50, 1442–1450. http://dx.doi.org/10.1037/a0030583

McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Jr., Kawas, C. H., . . . Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the Na- tional Institute on Aging-Alzheimer’s Association workgroups on diag- nostic guidelines for Alzheimer’s disease. Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, 7, 263–269. http://dx.doi .org/10.1016/j.jalz.2011.03.005

Nicholas, H., Moran, P., Foy, C., Brown, R. G., Lovestone, S., Bryant, S., & Boothby, H. (2010). Are abnormal premorbid personality traits asso- ciated with Alzheimer’s disease? A case-control study. International Journal of Geriatric Psychiatry, 25, 345–351. http://dx.doi.org/10.1002/ gps.2345

O’Leary-Barrett, M., Topper, L., Al-Khudhairy, N., Pihl, R. O., Castellanos-Ryan, N., Mackie, C. J., & Conrod, P. J. (2013). Two-year impact of personality-targeted, teacher-delivered interventions on youth internalizing and externalizing problems: A cluster-randomized trial. Journal of the American Academy of Child and Adolescent Psychiatry, 52, 911–920. http://dx.doi.org/10.1016/j.jaac.2013.05.020

Piedmont, R. L. (2001). Cracking the plaster cast: Big Five personality change during intensive outpatient counseling. Journal of Research in Personality, 35, 500 –520. http://dx.doi.org/10.1006/jrpe.2001.2326

Pocnet, C., Rossier, J., Antonietti, J. P., & von Gunten, A. (2011). Per- sonality changes in patients with beginning Alzheimer disease. The Canadian Journal of Psychiatry, 56, 408 – 417. http://dx.doi.org/10 .1177/070674371105600704

Rankin, K. P., Baldwin, E., Pace-Savitsky, C., Kramer, J. H., & Miller, B. L. (2005). Self awareness and personality change in dementia. Jour- nal of Neurology, Neurosurgery, and Psychiatry, 76, 632– 639. http:// dx.doi.org/10.1136/jnnp.2004.042879

Resnick, S. M., Bilgel, M., Moghekar, A., An, Y., Cai, Q., Wang, M. C., . . . Albert, M. S. (2015). Changes in A� biomarkers and associations with APOE genotype in 2 longitudinal cohorts. Neurobiol- ogy of Aging, 36, 2333–2339. http://dx.doi.org/10.1016/j.neurobiolaging .2015.04.001

Richman, M. D. (1989). Stability of personality traits in the demented elderly. Dissertation Abstracts International, 50, 5367.

Robins Wahlin, T. B., & Byrne, G. J. (2011). Personality changes in Alzhei- mer’s disease: A systematic review. International Journal of Geriatric Psychiatry, 26, 1019 –1029. http://dx.doi.org/10.1002/gps.2655

Rosenberg, P. B., Mielke, M. M., Han, D., Leoutsakos, J. S., Lyketsos, C. G., Rabins, P. V., . . . Tschanz, J. T. (2012). The association of psychotropic medication use with the cognitive, functional, and neuropsychiatric trajec- tory of Alzheimer’s disease. International Journal of Geriatric Psychiatry, 27, 1248 –1257. http://dx.doi.org/10.1002/gps.3769

Sander, J., Schmiedek, F., Brose, A., Wagner, G. G., & Specht, J. (2017). Long-term effects of an extensive cognitive training on personality development. Journal of Personality, 85, 454 – 463. http://dx.doi.org/10 .1111/jopy.12252

Sapkota, S., Wiebe, S. A., Small, B. J., & Dixon, R. A. (2016). Apolipo- protein E and Clusterin can magnify effects of personality vulnerability on declarative memory performance in non-demented older adults. In- ternational Journal of Geriatric Psychiatry, 31, 502–509. http://dx.doi .org/10.1002/gps.4355

Smith-Gamble, V., Baiyewu, O., Perkins, A. J., Gureje, O., Hall, K. S., Ogunniyi, A., . . . Hendrie, H. C. (2002). Informant reports of changes in personality predict dementia in a population-based study of elderly African Americans and Yoruba. The American Journal of Geriatric Psychiatry, 10, 724 –732. http://dx.doi.org/10.1097/00019442- 200211000-00011

Sollberger, M., Neuhaus, J., Ketelle, R., Stanley, C. M., Beckman, V., Growdon, M., . . . Rankin, K. P. (2011). Interpersonal traits change as a function of disease type and severity in degenerative brain diseases.

T hi

s do

cu m

en t

is co

py ri

gh te

d by

th e

A m

er ic

an P

sy ch

ol og

ic al

A ss

oc ia

ti on

or on

e of

it s

al li

ed pu

bl is

he rs

. T

hi s

ar ti

cl e

is in

te nd

ed so

le ly

fo r

th e

pe rs

on al

us e

of th

e in

di vi

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us er

an d

is no

t to

be di

ss em

in at

ed br

oa dl

y.

11PERSONALITY AND ALZHEIMER’S DISEASE

Journal of Neurology, Neurosurgery, and Psychiatry, 82, 732–739. http://dx.doi.org/10.1136/jnnp.2010.205047

Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., . . . Phelps, C. H. (2011). 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. Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, 7, 280 –292. http://dx.doi.org/ 10.1016/j.jalz.2011.03.003

Steinberg, S. I., Negash, S., Sammel, M. D., Bogner, H., Harel, B. T., Livney, M. G., . . . Arnold, S. E. (2013). Subjective memory complaints, cognitive performance, and psychological factors in healthy older adults. American Journal of Alzheimer’s Disease and Other Dementias, 28, 776 –783. http://dx.doi.org/10.1177/1533317513504817

Stephan, Y., Sutin, A. R., & Terracciano, A. (2014). Physical activity and personality development across adulthood and old age: Evidence from two longitudinal studies. Journal of Research in Personality, 49, 1–7. http://dx.doi.org/10.1016/j.jrp.2013.12.003

Strauss, M. E., & Pasupathi, M. (1994). Primary caregivers’ descriptions of Alzheimer patients’ personality traits: Temporal stability and sensitivity to change. Alzheimer Disease and Associated Disorders, 8, 166 –176. http://dx.doi.org/10.1097/00002093-199408030-00003

Strauss, M. E., Pasupathi, M., & Chatterjee, A. (1993). Concordance between observers in descriptions of personality change in Alzheimer’s disease. Psychology and Aging, 8, 475– 480. http://dx.doi.org/10.1037/ 0882-7974.8.4.475

Sutin, A. R., Stephan, Y., Luchetti, M., Artese, A., Oshio, A., & Terrac- ciano, A. (2016). The five-factor model of personality and physical inactivity: A meta-analysis of 16 samples. Journal of Research in Personality, 63, 22–28. http://dx.doi.org/10.1016/j.jrp.2016.05.001

Sutin, A. R., Stephan, Y., Luchetti, M., & Terracciano, A. (2017). Self- reported personality traits are prospectively associated with proxy- reported behavioral and psychological symptoms of dementia at the end of life. International Journal of Geriatric Psychiatry. Advance online publication. http://dx.doi.org/10.1002/gps.4782

Sutin, A. R., Stephan, Y., & Terracciano, A. (2017). Facets of Conscien- tiousness and risk of dementia. Psychological Medicine. Advance online publication. http://dx.doi.org/10.1017/S0033291717002306

Tang, T. Z., DeRubeis, R. J., Hollon, S. D., Amsterdam, J., Shelton, R., & Schalet, B. (2009). Personality change during depression treatment: A placebo-controlled trial. Archives of General Psychiatry, 66, 1322–1330. http://dx.doi.org/10.1001/archgenpsychiatry.2009.166

Terracciano, A., An, Y., Sutin, A. R., Thambisetty, M., & Resnick, S. M. (2017a). Personality change in the pre-clinical phase of Alzheimer’s disease. Journal of the American Medical Association Psychiatry. Advance online publication. http://dx.doi.org/10.1001/jamapsychiatry.2017.2816

Terracciano, A., Costa, P. T., Jr., & McCrae, R. R. (2006). Personality plasticity after age 30. Personality and Social Psychology Bulletin, 32, 999 –1009. http://dx.doi.org/10.1177/0146167206288599

Terracciano, A., Iacono, D., O’Brien, R. J., Troncoso, J. C., An, Y., Sutin, A. R., . . . Resnick, S. M. (2013). Personality and resilience to Alzhei- mer’s disease neuropathology: A prospective autopsy study. Neurobiol- ogy of Aging, 34, 1045–1050. http://dx.doi.org/10.1016/j.neurobiolaging .2012.08.008

Terracciano, A., Lobina, M., Piras, M. G., Mulas, A., Cannas, A., Meire- lles, O., . . . Schlessinger, D. (2011). Neuroticism, depressive symptoms, and serum BDNF. Psychosomatic Medicine, 73, 638 – 642. http://dx.doi .org/10.1097/PSY.0b013e3182306a4f

Terracciano, A., McCrae, R. R., Brant, L. J., & Costa, P. T., Jr. (2005). Hierarchical linear modeling analyses of the NEO-PI-R scales in the Baltimore Longitudinal Study of Aging. Psychology and Aging, 20, 493–506. http://dx.doi.org/10.1037/0882-7974.20.3.493

Terracciano, A., Stephan, Y., Luchetti, M., Albanese, E., & Sutin, A. R. (2017). Personality traits and risk of cognitive impairment and dementia. Journal of Psychiatric Research, 89, 22–27. http://dx.doi.org/10.1016/j .jpsychires.2017.01.011

Terracciano, A., Stephan, Y., Luchetti, M., & Sutin, A. R. (2017). Cogni- tive impairment, dementia, and personality stability among older adults. Assessment. Advance online publication. http://dx.doi.org/10.1177/ 1073191117691844

Terracciano, A., Sutin, A. R., An, Y., O’Brien, R. J., Ferrucci, L., Zon- derman, A. B., & Resnick, S. M. (2014). Personality and risk of Alz- heimer’s disease: New data and meta-analysis. Alzheimer’s and Demen- tia: The Journal of the Alzheimer’s Association, 10, 179 –186. http://dx .doi.org/10.1016/j.jalz.2013.03.002

Torrente, F., Pose, M., Gleichgerrcht, E., Torralva, T., López, P., Cetkovich-Bakmas, M., & Manes, F. (2014). Personality changes in dementia: Are they disease specific and universal? Alzheimer Disease and Associated Disorders, 28, 261–268. http://dx.doi.org/10.1097/WAD .0000000000000030

Wang, H. X., Karp, A., Herlitz, A., Crowe, M., Kåreholt, I., Winblad, B., & Fratiglioni, L. (2009). Personality and lifestyle in relation to dementia incidence. Neurology, 72, 253–259. http://dx.doi.org/10.1212/01.wnl .0000339485.39246.87

Whitmer, R. A., Sidney, S., Selby, J., Johnston, S. C., & Yaffe, K. (2005). Midlife cardiovascular risk factors and risk of dementia in late life. Neurology, 64, 277–281. http://dx.doi.org/10.1212/01.WNL.000014 9519.47454.F2

Wilson, R. S., Arnold, S. E., Schneider, J. A., Kelly, J. F., Tang, Y., & Bennett, D. A. (2006). Chronic psychological distress and risk of Alz- heimer’s disease in old age. Neuroepidemiology, 27, 143–153. http://dx .doi.org/10.1159/000095761

Wilson, R. S., Barnes, L. L., Bennett, D. A., Li, Y., Bienias, J. L., Mendes de Leon, C. F., & Evans, D. A. (2005). Proneness to psychological distress and risk of Alzheimer disease in a biracial community. Neurol- ogy, 64, 380 –382. http://dx.doi.org/10.1212/01.WNL.0000149525 .53525.E7

Wilson, R. S., Begeny, C. T., Boyle, P. A., Schneider, J. A., & Bennett, D. A. (2011). Vulnerability to stress, anxiety, and development of dementia in old age. The American Journal of Geriatric Psychiatry, 19, 327–334. http://dx.doi.org/10.1097/JGP.0b013e31820119da

Wilson, R. S., Boyle, P. A., Yu, L., Segawa, E., Sytsma, J., & Bennett, D. A. (2015). Conscientiousness, dementia related pathology, and tra- jectories of cognitive aging. Psychology and Aging, 30, 74 – 82. http:// dx.doi.org/10.1037/pag0000013

Wilson, R. S., Evans, D. A., Bienias, J. L., Mendes de Leon, C. F., Schneider, J. A., & Bennett, D. A. (2003). Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology, 61, 1479 –1485. http://dx.doi.org/10.1212/01.WNL.0000096167.56734.59

Wilson, R. S., Schneider, J. A., Arnold, S. E., Bienias, J. L., & Bennett, D. A. (2007). Conscientiousness and the incidence of Alzheimer disease and mild cognitive impairment. Archives of General Psychiatry, 64, 1204 –1212. http://dx.doi.org/10.1001/archpsyc.64.10.1204

Yoneda, T., Rush, J., Berg, A. I., Johansson, B., & Piccinin, A. M. (2016). Trajectories of personality traits preceding dementia diagnosis. The Journals of Gerontology. Advance online publication. http://dx.doi.org/ 10.1093/geronb/gbw006

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12 TERRACCIANO AND SUTIN