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Comprehensive Psychiatry 52 (2011) 659–661 www.elsevier.com/locate/comppsych

Does late onset depression predispose to dementia? A retrospective, case-controlled study

Irit Ohanna, Hava Golander, Yoram Barak⁎

Sackler School of Medicine, Tel-Aviv University, 59100 Israel

Abstract

Background: Recent research suggests that there are clinical and biologic characteristics typical of late onset depression (LOD). Furthermore, evidence has been put forward that LOD may be a prodrome of dementia. Objective: This study aims to assess the association between LOD and the development of dementia. Setting: The study was conducted in a tertiary care, university-affiliated mental health center providing services for an urban catchment population of 800 000 subjects. Method: A retrospective, case-controlled study was used. Results: Fifty-one patients with LOD who developed dementia at least 1 year after diagnosis of LOD were defined as the index group: 18 males and 33 females, with a mean age of 75.4 ± 9.2 years. These were compared with 51 patients with LOD who did not develop dementia during a 10-year follow-up period. Dementia types were as follows: 73% Alzheimer disease, 24% vascular and mixed dementia, and 3% Parkinson dementia.

Patients with LOD who developed dementia were significantly characterized by having longer hospitalization for their first depressive episode (P = .048), having a family history of dementia (P = .022), and having been exposed to the Holocaust as young adults (P = .013). Conclusions: Patients with a history of significant traumatic experience in early life and a prolonged onset of depression may be at particular risk of developing dementia. This issue requires further long-term prospective studies. © 2011 Elsevier Inc. All rights reserved.

1. Introduction

Affective disorders, particularly depression and cognitive dysfunction, are among the mental health problems adverse- ly impacting the lives of elderly people. Both have severe consequences, including decreased quality of life, functional disability, increased use of general medical as well as mental health services, and associated direct and indirect mortality. Late onset depression (LOD) is closely associated with cognitive impairment. However, it is not known whether depression leads to cognitive decline or, in more severe cases, to dementia [1].

Conflict of interest declaration: none Description of authors' roles: I Ohanna designed the study, collected the

data, and helped in writing the paper. H Golander supervised the designing of this study and assisted with writing the article. Y Barak was responsible for the statistical design of the study and wrote the paper.

⁎ Corresponding author. Abarbanel Mental Health Center, Bat-Yam, Israel. Tel.: +972 3 5552738; fax: +972 3 5552738.

E-mail address: [email protected] (Y. Barak).

0010-440X/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.comppsych.2010.10.016

Although studies have shown that depression and dementia frequently coexist [2], causality remains contro- versial. Several case-control studies have tested the associ- ation between dementia and depression as early as 1986. Speck et al reported that patients with Alzheimer disease (AD) were more likely than nondemented patients to have a history of depression, with later reports suggesting doubling of dementia risk for patients with a history of depression [3].

Despite the published studies reporting a higher risk of dementia for patients with a history of LOD, there are several observations that do not complement this hypothesis. First, only depressive episodes developing for the first time in close temporal proximity to dementia onset were positively associated with dementia risk [4,5]. Thus, depression may be only a prodromal feature of dementia rather than a risk factor. Other studies, however, have found the opposite [6], reporting that the length of the interval between the diagnoses of depression and AD was positively associated with an increased risk of developing AD, concluding that depression was a risk factor rather than a prodrome of

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dementia. Because these contrasting views are not reconciled in the literature, we aimed to approach this question using a unique database of all tertiary care patients in a specific urban catchment area in Israel.

2. Method

The present work was designed as a retrospective, case- controlled study based on medical charts review. All medical charts are computerized at the Abarbanel Mental Health Center, Bat-Yam, Israel, and these served as the sample source. This tertiary care center is a large, urban, university- affiliated psychiatric hospital. The hospital has no selective admission policy and is the only tertiary care psychogeriatric facility in the area. At our center, there are 330 inpatient beds and 60 day patients as well as a large outpatient clinic. The center serves an urban catchment area of approximately 850 000 people of which 14.3% are 65 years or older and possibly includes most potential incidence cases in our area.

The study was approved by the local institutional review board.

The index group was defined as that encompassing patients who were 50 years or older at the first-ever diagnosis of a major depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria) as well as being diagnosed as having dementia [7]. Dementia had to be diagnosed a minimum of 12 months after onset of the depressive episode. The comparison group was that of patients with LOD (onset of first-ever depressive episode after the age of 50 years) who were followed up for a period of 10 years during which no dementia had developed. The groups were matched for year of birth, sex, and education. The study covered the period from January 1990 to December 2001.

Each medical record was assessed for the following parameters: (a) sociodemographic (age, sex, country of birth, year of immigration, education, marital status, no. of children, family history of any neuropsychiatric disorder, and history of Holocaust experience), (b) health (physical disorders, current medication regimen, and history of head trauma), (c) depression (age at onset, duration of episodes, hospitalizations, cognitive status, and treatment) and (d) dementia ( age at onset, type, and treatment).

2.1. Statistical analysis

Data were analyzed using the independent-samples approach. The 2-tailed t and nonparametric (Wilcoxon) tests were undertaken to test for differences between the evaluations for quantitative parameters. Examination of differences between the categorical parameters was based on the Pearson and Fisher exact tests. The analyses were a test of univariate association of independent variables. All tests applied were 2-tailed, and a P value of 5% or less was considered statistically significant.

The data were analyzed using the Statistical Analysis System software (SAS Institute, Cary, NC) [8].

3. Results

The Abarbanel Mental Health Center computerized files provided a preliminary database of 1500 patients having their first-ever major depressive episode after the age of 50 years. Of these, 51 fulfilled the inclusion criteria for the index group. Fifty-one age-, sex-, and education-matched subjects were randomly selected as the comparison group.

For the index group, the mean age was 75.5 ± 9.2 years (range, 54-96 years); there were 33 female (65%) and 18 male (35%) patients. The mean years of education for the group was 8.9 ± 3.2. Duration of first episode of depression was 5.8 ± 11.1 months, and mean severity of the depressive episode as reflected by the Clinical Global Impression– Severity scale was 5.2 ± 1.4. Most patients, 46 (90%), had intact cognitive functioning during the depressive episode. There were 24 (47%) Holocaust survivors in this group. Family history of dementia was established in 5 (10%) of the patients. The minority of patients in the index group, 2 (4%), was born in Israel.

The distribution of dementias in this group was as follows: 37 (73%) cases, AD; 12 (24%), vascular and mixed dementia; and 2 (3%), Parkinson disease dementia. Duration of time elapsed between diagnosis of LOD and dementia was 6.2 ± 4.8 years (range, 1-25 years).

For the comparison group, the mean age was 74.8 ± 9.8 years (range, 52-96 years); there were 33 female (65%) and 18 male (35%) patients. The mean years of education for the group was 9.1 ± 3.6. Duration of first episode of depression was 2.8 ± 2.9 months, and mean severity of the depressive episode as reflected by the Clinical Global Impression– Severity scale was 5.3 ± 1.0. Most patients, 50 (98%), had intact cognitive functioning during the depressive episode. There were 14 (28%) Holocaust survivors in this group. Family history of dementia was negative for all patients. The minority of patients in the comparison group, 9 (18%), was born in Israel.

There are 3 statistically significant differences between the index and comparison groups: (a) family history of dementia, χ21 = 53, P = .022; (b) duration of first-ever LOD episode, χ2101 = 1.8, P = .048; and (c) exposure to the Holocaust, χ22 = 8.6, P = .013.

4. Discussion

A meta-analysis of the data on history of depression as a risk factor for dementia as well as the available evidence on the hypotheses proposed to explain the association between history of depression and dementia was undertaken by Jorm [3] in 2001. The meta-analysis found evidence to support an association from both case-control (relative risk, 2.01) and

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prospective (relative risk, 1.87) studies. However, the evidence did not clearly support any one hypothesis explaining the association. The 2 most likely hypotheses were that (1) depression may be a prodrome of dementia and (2) depression brings forward the clinical manifestation of dementing diseases. The possibility that history of depres- sion is a risk factor for dementia need be considered seriously, and explanations of the association need be researched [3]. More specifically, close relationship between the depressions of late life (LOD) and dementia has been postulated. Schweitzer et al [9] argue that studies of LOD and dementia offer persuasive evidence that LOD is often a prodromal disorder for dementia.

The present study was a retrospective, case-control attempt to add to the growing evidence on the possible relationship between LOD and the development of dementia. Our findings are that family history of dementia in patients with LOD was associated with greater risk of developing dementia. This is in line with many well-established publications. However, 2 findings are novel; the duration of the first LOD episode was associated with dementia development and exposure to the Holocaust. We may tentatively suggest that the duration of the first LOD episode may indirectly reflect a more severe onset of depression— especially because we analyzed cases from a tertiary care psychiatric service. Severity of this episode may have been more likely to bring forward the clinical manifestation of dementing diseases as put forward by Jorm [3]. The exposure to the Holocaust is a unique finding in this specific sample that has many possible explanations such as lack of protective factors (education, nutrition, and more), head injuries, infections, and the traumatic experience developing into posttraumatic stress disorder (PTSD). Recent evidence suggests that PTSD adversely affects memory [10]. Furthermore, Yaffe et al [11] found that older veterans with PTSD had nearly a 2-fold increased risk for dementia compared with their counterparts without PTSD. This did not appear to be associated with a particular dementia type but rather had an “across-the-board effect” for all dementias, including vascular dementia and AD. To examine the question of whether PTSD might carry an increased risk for dementia, these researchers used data from the Department of Veterans Affairs National Patient Care Database. The retrospective cohort study included 181 093 veterans 55 years and older without dementia at baseline and compared rates of newly diagnosed dementia or cognitive

impairment in 53 155 subjects with a diagnosis of PTSD and 127 938 subjects without PTSD. The subjects' mean age at baseline was 68.8 years, and most were males. After adjustment for demographics and medical and psychiatric comorbidities, patients with PTSD were still nearly twice as likely to develop incident dementia (hazard ratio, 1.77; 95% confidence interval, 1.7-1.9). The results were similar when investigators excluded subjects with a history of traumatic brain injury, substance abuse, or depression [11].

In conclusion, despite the limitations inherent in a retrospective analysis of a small and specific sample, the present study offers further support to the association between LOD and risk of developing dementia. We also tentatively suggest that traumatic experiences need be studied as confounders in the complex interplay between depression and dementia.

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