Abstract
Late-life depression, as a potential marker of pre-dementia, has seldom been explored by symptom dimension and sex, despite sexual dimorphic differences. This study aimed to examine whether specific depressive dimensions were associated with pre-Alzheimer’s disease dementia (pre-AD), separately for women and men. Data were drawn from 5617 (58% women) community-dwellers aged 65+ recruited in 1999–2000 and followed at 2-year intervals for 12 years. We used Cox proportional hazard models to study associations between time-dependent Centre for Epidemiologic Studies-Depression Scale (CES-D) symptom dimensions (namely somatic, depressed, positive affect, and interpersonal challenge) and pre-AD, defined retrospectively from validated diagnoses established 3.5 (IQR: 3.2–4.0) years onwards. Analyses were performed according to overall depressive symptomatology (DS+: CES-D score ≥ 16) and antidepressant/anxiolytic medication use (AA). Results indicated that in DS+ women only, all four dimensions were significantly associated with pre-AD in the AA- group, in particular somatic item ‘Mind’ and depressed affect items ‘Depressed’ and ‘Blues’. The most depression-specific dimension, depressed affect, was also significantly associated with pre-AD in the DS– AA- women (HR:1.28, 95%CI: 1.12;1.47). In both sexes, in the DS– groups somatic affect was the most robust pre-AD marker, irrespective of treatment (women: HR = 1.22, 95%CI: 1.08;1.38; men: HR = 1.30, 95%CI: 1.14;1.48). Our findings highlight sex-specific associations between depressive symptom dimensions and pre-AD, modulated by depressive symptomatology and treatment. Assessment of specific symptom dimensions taking into account overall symptomatology and treatment could help identify and target high-risk AD-dementia profiles for interventions.
Highlights
Depressive symptoms are common in elderly people and depression is known to affect up to 50% of persons with Alzheimer’s disease (AD) dementia[1,2]
The somatic and depressed affect dimensions were significantly associated with pre-Alzheimer’s disease dementia (pre-AD) irrespective of depressive symptomatology (DS), whereas the remaining two dimensions were associated in the DS+ group only (Table 3)
In the DS+ group, the four dimensions were significantly associated with pre-AD in the untreated women only
Summary
Depressive symptoms are common in elderly people and depression is known to affect up to 50% of persons with Alzheimer’s disease (AD) dementia[1,2]. Findings suggest that depression acts as a marker of pre-dementia rather than as a risk factor per se, potentially sharing common underlying causes such as vascular disease or inflammatory processes[5,6,7,9,10]. Several prospective studies suggest that late-life depressive symptoms assessed mostly using the Centre for Epidemiologic Studies-Depression Scale (CES-D) may be associated with an increased dementia risk within a narrow time-frame (between 5 and 10 years) preceding dementia onset[6,9,11,12,13].
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