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EDITORIAL

Dementias and depression late in life: Beyond observed associations to underlying mechanismpsyg_322 1..3

Hiromi SHIRAISHI

Faculty of Life Design, Toyo University, Tokyo, Japan

Correspondence: Dr Hiromi Shiraishi MD PhD, Faculty of Life Design, Toyo University, Tokyo, 48-1 Oka, Asaka-City, Saitama Prefecture 351-8510, Japan. Email: [email protected]

Pure Types Are Rare1 is the title of a book written by Irwin Silverman about the so-called anti-psychiatry movement that was around in the 1980s. In that book, Silverman insisted that mental illness was not the product of a damaged brain, but rather of social hazards or human prejudice. However, my interest here is not anti-psychiatry but geriatric psychiatry. I have often had difficulties making clinical diagnoses of people with dementia. Textbooks teach us that there are several types of dementias, such as Alzhe- imer’s disease (AD) and vascular dementia (VaD), and diagnostic criteria have been established for each type of dementia. So, it seems that for typical cases a trained psychiatrist shouldn’t usually have any prob- lems making a differential diagnosis. However, criteria or clinical symptoms sometimes betray us and we may find that the neuropathological diagnosis of a patient who had been diagnosed clinically as having AD in fact indicates Lewy body disease. Moreover, those of us who believed that AD and VaD were dif- ferent entities were bewildered when we first heard that multiple infarctions and ischemic lesions were often found in patients diagnosed clinically as AD and that senile plaques and neurofibrillary tangles were often found in patients diagnosed clinically as VaD. Since the publication of the Nun study,2 a longitudinal study of aging and AD, the relationship between AD and VaD has been thoroughly examined and it seems that AD lesions and vascular lesions independently and synergistically affect the brain to the point of dementia. Another finding has been the concept of

vascular cognitive impairment (VCI),3 which is similar to that of mild cognitive impairment (MCI). Although the concept of VCI still seems to require clarification,4

the promulgation of VCI and MCI has provided us with a new way of looking at patients in terms of clinical symptomatology. So, theoretically, it can be said that ‘pure types are rare’, but that does not mean that the situation is chaotic: there is the promise of a new discovery.

DEPRESSION IN LATE LIFE Depression is more complicated. Depression can occur at any age, for example in boys in elementary school as well as in very old residents in a nursing home. This wide age range suggests that there are different entities behind the similar clinical expression of depression. According to statistics compiled by the Japanese Government, the number of patients with depression has increased from 420 000 in 1999 to 900 000 in 2005.5 No one can deny that certain psy- chosocial factors have contributed significantly to this marked increase. However, it has long been recog- nized that depression is caused by brain dysfunction. For example, a recent survey of old community resi- dents that used the Geriatric Depression Scale revealed that the older the resident, the higher the incidence of a depressive state.6 This suggests that the brain itself is vulnerable in some aspects and that depression is not pure at all. Regardless, depression has attracted the attention of many researchers in geriatric psychiatry, as well as in other fields. I am

doi:10.1111/j.1479-8301.2010.00322.x PSYCHOGERIATRICS 2010; 10: 1–3

impressed by the number of papers on depression in later life that have been submitted to Psychogeriatrics in recent times.

In 1991, the National Institutes of Health held a Consensus Development Conference on Diagnosis and Treatment of Depression in Late Life to address the epidemiology, pathogenesis, pathophysiology, prevention, and treatment of depression in the elderly. The conclusions reached were as follows:7

1. Depression in late life occurs in the context of numerous social and physical problems that often obscure or complicate diagnosis and impede man- agement of the illness. 2. Because there is no specific diagnostic test for depression, an attentive and focused clinical assess- ment is essential for diagnosis. 3. Depressed elderly people should be treated vigor- ously with sufficient doses of antidepressants and for a sufficient length of time to maximize the likelihood of recovery. 4. Electroconvulsive therapy and psychosocial treat- ments also can be effective in the treatment of elderly depressed patients. 5. Estimates of the prevalence of depression vary widely, but the highest rates are in nursing homes and other residential settings and staff in many of these facilities are not equipped to recognize or treat depressed patients.

DEPRESSIVE STATES AMONG PEOPLE WITH DEMENTIA The consensus statement summarized the newest knowledge from all research areas and recognized that depression is a serious mental health problem that the older generation faces; however, in terms of a relationship between depression and dementia, the only comment was the following: ‘In elderly people, the co-occurrence of physical conditions (e.g., stroke, cancer, dementia) and depression has been con- firmed in numerous studies’.7 In 1997, when an update was published,8 very little was written regard- ing this issue. However, soon after, many began to point out that the relationship between dementia and depression late in life was not weak. For example, Boland (2000)9 summarized research that had been published up to 2000 and concluded that comorbid depression is common in all types of dementia. Thorpe et al.10 reviewed Medline articles and found

that the prevalence of depressive syndromes was increased in dementia. Both groups noted that the depressive symptoms seen in dementia were often a little different to ‘classic’ depression. Many have also noted this difference and a various names have been given to the depressive state in dementia, including subsyndromal symptomatic depression, subclinical depression, mild depression, subthreshold depres- sion, minor depressive disorder, or subdysthymic dis- order.8 Although treatment designed for ‘classic type’ depression is often anecdotally said to be less effica- cious in the treatment of depression associated with dementia, a trial of antidepressant therapy should be considered. According to Tune,11 the ‘rules’ for the treatment of depression in dementia are: (i) start low, go slower; (ii) pay attention to the cognitive toxicity of all medication combinations; and (iii) depressive symptoms do not persist as long as in cognitively intact patients. Tune11 recommends that selective serotonin reuptake inhibitors (SSRIs) that have cognitive-enhancing effects, such as fluoxetine and sertraline, be used as ‘first-line’ antidepressants.

RELATIONSHIP BETWEEN DEMENTIA AND DEPRESSION LATE IN LIFE It is true that depression often follows dementia, but there is also the possibility that it enhances a person’s vulnerability to dementia. Jorm12 reviewed the litera- ture and found six hypotheses that may explain the association between depression and dementia: (i) depression treatments are a risk factor for dementia; (ii) dementia and depression share common risk factors; (iii) depression is a prodrome of dementia; (iv) depression is an early reaction to cognitive decline; (v) depression affects the threshold for manifesting dementia; and (vi) depression is a causal factor in dementia. Jorm12 conducted a meta-analysis and found that depression was associated with an increased risk of subsequent dementia in both case control and prospective studies (95% confidence intervals for relative risk 1.16–3.50 and 1.08–3.20, respectively). He concluded that there is sufficient evidence to take seriously the possibility that depres- sion is a risk factor for dementia and cognitive decline.12 There have been other reports that support the notion that depression heightens the risk of dementia. For example, Nakano et al.13 examined the executive function in the medicated, remitted state of major depression as a part of their comprehensive

Editorial

clinical research into mood disorders ( Juntendo Uni- versity Mood Disorder Project) and found that there certain cognitive dysfunction remained even in remit- ted patients. Nakano et al.13 reported that this dys- function seemed to be associated with vascular lesions in the white matter. They also discussed the notion that the vulnerability resulting from the brain dysfunction in depressed patients in late life acts as a risk factor for dementia.

Depression in late life is not pure at all, and the relationship between depression and dementia is not simple either, but behind the apparent diversity and complexity I believe there will be a pure and simple relationship between depression and dementia.

REFERENCES 1 Silverman I. Pure Types Are Rare: Myths and Meanings of

Madness. New York: Praeger Publishers, 1983. 2 Snowdon DA, Greiner LH, Mortimer JA et al. Brain infarction and

the clinical expression of Alzheimer’s disease. The Nun study. JAMA 1997; 277: 813–817.

3 Sachdev P. Vascular cognitive disorder. Int J Geriatr Psychiatry 1999; 14: 402–403.

4 Selnes OA, Vinters HV. Vascular cognitive impairment. Nat Clin Pract Neurol 2006; 2: 538–547.

5 Ministry of Health, Labour and Welfare. Patient Survey 2005. http://www.mhlw.go.jp/english/database/db-hss/ps.html

6 Paísson SP, Ostling S, Skoog I. The incidence of first-onset depression in a population followed from the age of 70 to 85. Psychol Med 2001 Oct; 31 (7): 1159–1168.

7 National Institutes of Health. Diagnosis and Treatment of Depression in Late Life. http://www.nlm.nih.gov/medlineplus/. (This statement was originally published as: Diagnosis and Treatment of Depression in Late Life. NIH Consensus Statement 1991 Nov 4–6; 9 (3): 1–27.)

8 Lebowittz BD, Pearson JL, Schneider LS et al. Diagnosis and treatment of depression in late life. Consensus statement update. JAMA 1997; 278: 1186–1190.

9 Boland RJ. Depression in Alzheimer’s Disease and Other Dementias. Curr Psychiatry Rep 2000 Oct; 2 (5): 427–433.

10 Thorpe L, Groulx B. Depressive syndromes in dementia. Can J Neurol Sci 2001; 28 (Suppl. 1): S83–S95.

11 Tune LE. Depression and Alzheimer’s disease. Depress Anxiety 1998; 8 (Suppl. 1): 91–95.

12 Jorm AF. Is depression a risk factor for dementia or cognitive decline? A review. Gerontology 2000; 46: 219–227.

13 Nakano Y, Baba H, Maeshima H et al. Executive dysfunction in medicated, remitted state of major depression. J Affect Disord 2005; 111: 46–51.

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