Depressive symptoms and multiple markers of brain aging in community-dwelling older adults

Late-life depressive symptoms have been associated with structural brain changes and cognitive impairment, but prior studies have typically examined individual markers of brain aging in isolation. This study examined the associations between depressive symptoms and multiple markers of brain aging in a population-based cohort of community-dwelling older adults. Baseline data from 2,746 participants with complete data on depressive symptoms, neuroimaging measures, cognitive assessment, and covariates were analyzed cross-sectionally. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). White matter hyperintensity (WMH) volume and hippocampal volume were derived from structural magnetic resonance imaging, and global cognitive performance was assessed using the Seoul Neuropsychological Screening Battery-Core (SNSB-C). Multivariable linear regression models were used to evaluate associations after adjustment for demographic, cardio-metabolic, and lifestyle factors. Higher depressive symptom burden was associated with greater WMH burden, smaller hippocampal volume, and poorer global cognitive performance. Associations with WMH burden and cognitive performance remained consistent after additional adjustment for vascular comorbidities and in sensitivity analyses modeling depressive symptoms as a dichotomous exposure using a CES-D cutoff of ≥16, whereas associations with hippocampal volume were more modest. These findings suggest that depressive symptoms in later life are related to multiple domains of brain aging, with the most consistent associations observed for WMH burden and cognitive performance. Further longitudinal studies are needed to clarify temporal relationships underlying these associations.