Patients with late-onset depression have poor cognitive function at old age.

Abstract

To the Editor: It has been suggested that late-onset depression is an early manifestation of cognitive impairment.1 The “vascular depression” hypothesis2 argues that late-onset depression is caused by cardiovascular disease. Moreover, several studies have suggested that atherosclerosis causes subclinical, ischaemic events in the brain, which contributes to cognitive decline in old age.3–4 This could explain why late-onset depression is related to a poor cognitive function. In contrast, early-onset depression is not associated with cognitive impairment and is thought to be the result of a genetic predisposition.5 We explored whether late-onset depression is an early manifestation of cognitive impairment. If confirmed, this would support the idea that late-onset depression and cognitive impairment are outcomes of a similar disease mechanism. The study was approved by the medical ethical committee of the Free University Amsterdam. All subjects were admitted to the Psychiatric Centre Amsterdam, location Valerius Clinic, a general psychiatric hospital in the Netherlands, between 1990 and 1992. At that time, all had a primary diagnosis of major depressive disorder. Subjects were categorised as having late-onset depression (age of onset of first depression ≥55 years) or early-onset depression (age of onset of first depression <55 years). In 1999, all 62 subjects were approached for this study, 5 refused to participate and 4 were lost to follow-up. During a home visit in 1999, presence or absence of DSM-IV criteria for major depressive disorder was determined with the Composite International Diagnostic Interview.6 Cognitive function was assessed with the Mini-Mental State Examination (MMSE).7 History of cardiovascular disease, defined as myocardial infarction, cerebrovascular accident, or heart failure, was obtained from the participant's general practitioner. On reexamination in 1999, the mean age of subjects with late-onset depression (n = 34) was 76.7 years and the subjects with early-onset depression (n = 19) had a mean age of 72.4 years (P = .028). The proportion of men and women and the social economical status of the participants with late-onset depression and early-onset depression were similar (all P > .05, data not shown). The proportion of subjects with cardiovascular disease was significantly higher in subjects with a history of late-onset depression as compared with subjects with a history of early-onset depression (44% vs 16%, P = .037). A family history of depression was significantly more often present in patients with a history of early-onset depression as compared with subjects with a history of late-onset depression (63% vs 35%, P = .027). Table 1 shows that the MMSE score was significantly lower in subjects with a history of late-onset depression as compared to subjects with a history of early-onset depression (P = .004). Since there was an age difference between the groups, we stratified our analysis in different age bands. The difference in MMSE scores between subjects with a history of late-onset depression or a history of early-onset depression was present in all age bands. During the home visit, 4 out of 34 subjects with a history of late-onset depression and 3 out of 19 subjects with a history of early-onset depression were depressed. The difference in MMSE scores, between subjects with a history of late-onset depression and subjects with a history of early-onset depression was similar when we restricted our analysis to subjects who were not depressed during the home visit (25.5 points and 29 points respectively, P = .009). We explored whether late-onset depression is an early manifestation of cognitive impairment. Subjects with a history of late-onset depression had lower scores on the MMSE than subjects with a history of early-onset depression. As expected, we found that subjects with a history of late-onset depression had more cardiovascular disease than subjects with a history of early-onset depression.2 We also found that subjects with a history of late-onset depression were less likely to have a family history of depression, which is supported by earlier studies.5 These findings support the hypothesis that late-onset depression might be an early symptom of cognitive impairment, which could be caused by cardiovascular disease. Our data also support the hypothesis that late-onset depression is different from early-onset depression because of the difference in positive family history for depression. Taken together, these data show that late-onset depression and poor cognitive function are linked and suggest different biological mechanisms for late-onset versus early-onset depression. This is clinically important because it implies that distinct preventative and therapeutic interventions should be developed for late-onset depression.