Abstract
BACKGROUND: The precise relationship between depression and cognitive decline in older adults is unclear. We investigated the influence of apolipoprotein E (APOE)-epsilon4 genotype in modulating the effect of depressive symptoms on cognitive decline. METHODS: Prospective cohort study of 1,487 cognitively high-functioning Chinese older adults. Depressive symptoms (Geriatric Depression Scale score >/=5) and Mini-Mental State Examination (MMSE) were assessed at baseline, and cognitive decline (at least 1-point drop in MMSE) at 1-2 years after baseline. RESULTS: There was no significant difference in cognitive decline between depressed (32.9%) and nondepressed (31.5%) participants in the whole sample or among non-APOE-epsilon4 carriers. Among APOE-epsilon4 carriers, depressed participants showed more cognitive decline (40.0%) than their nondepressed counterparts (28.6%), odds ratio = 2.89, 95% confidence interval: 1.03-8.12; p = .04, after controlling for age, gender, education, vascular risk factors/events, smoking, alcohol drinking, physical functioning, subjective memory complaint, length of follow-up, and baseline MMSE scores (p for interaction = .03). CONCLUSIONS: Our study suggests that the presence of the APOE-epsilon4 allele significantly enhanced the risk of cognitive decline associated with depressive symptoms. This finding should be independently replicated in future studies.