Midlife vs Late-Life Depressive Symptoms and Risk of Dementia

Context:
Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia.

Objective:
To clarify the timing and nature of the association between depression and dementia.

Design:
- We examined depressive symptoms assessed in midlife (1964-1973) and late life (1994-2000) and the risks of dementia, Alzheimer disease (AD), and vascular dementia (VaD) (2003-2009) in a retrospective cohort study.
- Depressive symptoms were categorized as none, midlife only, late life only, or both.
- Cox proportional hazards models (age as timescale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD, or VaD.

Participants:
Thirteen thousand five hundred thirty-five (13,535) long-term Kaiser Permanente members.

Main Outcome Measure:
Any medical record diagnosis of dementia or neurology clinic diagnosis of AD or VaD.

Results
- Subjects had a mean (SD) age of 81.1 (4.5) years in 2003, 57.9% were women, and 24.2% were nonwhite.
- Depressive symptoms were present in 14.1% of subjects in midlife only, 9.2% in late life only, and 4.2% in both.
- During 6 years of follow-up, 22.5% were diagnosed with dementia (5.5% with AD and 2.3% with VaD).
- The adjusted hazard of dementia was increased by approximately 20% for midlife depressive symptoms only (hazard ratio, 1.19 [95% CI, 1.07-1.32]), 70% for late-life symptoms only (1.72 [1.54-1.92]), and 80% for both (1.77 [1.52-2.06]).
- When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a 2-fold increase in AD risk (hazard ratio, 2.06 [95% CI, 1.67-2.55]), whereas subjects with midlife and late-life symptoms had more than a 3-fold increase in VaD risk (3.51 [2.44-5.05]).

Conclusions:
- Depressive symptoms in midlife or in late life are associated with an increased risk of developing dementia.
- Depression that begins in late life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.