Depressive symptoms modeled across the life‐course are associated with higher risk of dementia and cognitive decline: A pooled cohort analysis: Epidemiology / Risk and protective factors in MCI and dementia. (7th December 2020) - Brenowitz, Willa D
Abstract: Background: Depression may be an important risk factor for dementia, but findings are controversial, partially because depression may be an early symptom of dementia. Most studies have only assessed depression symptoms at mid or late‐life, although depression can be a lifelong illness and effects may differ over the life‐course, with important prevention implications. We pooled data from 4 prospective cohorts spanning the life‐course to assess associations between life‐course depressive symptoms and risk of mild cognitive impairment (MCI)/dementia and cognitive decline. Method: We analyzed repeated Center for Epidemiologic Studies Depression Scale‐10 (CESD‐10) assessments for 15, 001 adults spanning early adult to mid‐life (CARDIA; N=5, 115), mid to late‐life (MESA; N=4, 515), and late‐life (CHS; N=5, 888 and Health ABC; N=3, 075). Using linear mixed models (LMMs), we imputed expected depressive symptom levels from age 20 until the end of follow‐up, then summarized these exposures in early adulthood (ages 20‐49), mid‐life (50‐69), and late‐life (70‐89) by time‐weighted averages (TWAs). Among CHS and Health ABC participants, we used Cox models and LMMs to estimate the associations of higher depressive TWAs from imputed depressive symptoms with incidence of MCI/dementia as well as cognitive trajectories, adjusting for age, sex, race/ethnicity, education, cohort, and anti‐depressant use. In preliminary analyses, depressive symptoms were categorized as low (CESD‐10= 0‐3; reference group), middle (CESD‐10= 4‐10) and high (CESD‐10 >10). Result: Increased risk of MCI/dementia was associated with elevated depressive TWAs in each life stage: early adulthood HR=1.59 (95% CI: 1.35, 1.87); mid‐life HR=1.94 (95%CI: 1.16, 3.26); and late‐life HR=1.77 (95%CI:1.42, 2.21) (Table 1). Higher TWAs in each life‐stage were also associated with faster rates of cognitive decline (all, p<0.05). When adjusted for depressive TWAs in the other life stages, elevated depressive TWAs in early adulthood (HR=1.73; 95%CI: 1.42, 2.11) and late‐life (HR=1.43; 95%CI: 1.08, 1.89) remained significantly associated with MCI/dementia and faster cognitive decline. Conclusion: Depressive symptoms imputed across the life‐course were associated with worse cognition, faster rates of cognitive decline and higher risk of dementia in late‐life. These findings are among the first to suggest that depressive symptoms in early adulthood are associated with higher risk of dementia, independent of the effects of late‐life depression.