Depressive Symptoms and Cognitive Decline in Community‐Dwelling Older Adults

OBJECTIVES: To examine the temporal association between depressive symptoms and cognitive functioning and estimate the effect measure modification of the apolipoprotein E (APOE) ?4 allele on this relationship. DESIGN: Prospective cohort study. SETTING: General community. PARTICIPANTS: Population‐based sample of 598 cognitively intact older adults aged 60 and older, with re‐assessments after 3 (N=479) and 6 years (N=412). MEASUREMENTS: Depressive symptoms (Symptom Checklist) and neurocognitive functioning (memory, Visual Verbal Learning Test; attention, Stroop Color–Word Test; processing speed, Letter Digit Substitution Test; general cognition, Mini‐Mental State Examination). Longitudinal associations were assessed using linear mixed models. The risk for cognitive impairment, no dementia (CIND) was examined using logistic regression. RESULTS: Adjusting for age, sex, education, and baseline cognition, the rate of change in memory z‐scores was 0.00, ?0.11, ?0.20, and ?0.37 for those in the lowest (reference group), second, third, and highest depressive symptom quartiles at baseline, respectively (P<.001 for highest vs lowest quartile). The odds ratios for developing CIND with amnestic features were 1.00, 0.87, 0.69, and 2.98 for the four severity groups (P=.05 for highest vs lowest quartile). Associations were strongest for those with persistent depressive symptoms, defined as high depressive symptoms at baseline and at least one follow‐up visit. Results were similar for processing speed and global cognitive function but were not as strong for attention. No APOE interaction was observed. CONCLUSION: Depression and APOE act independently to increase the risk for cognitive decline and may provide targets for prevention and early treatment.