Independent Effects of Apolipoprotein E and Cerebrovascular Burden on Later-Life Depression: The Wisconsin Longitudinal Study

Objective: Studies evaluating the effect of apolipoprotein E (APOE) on vascular depression are sparse, employ heterogeneous methods, and yield inconsistent results. One possibility is that APOE is a moderator of another predictor such as cerebrovascular burden. This longitudinal study examines the relationships between APOE, cerebrovascular burden, and depressive symptomatology in a large cohort sample from midlife to later life.

Methods: Data include 3,203 participants across 18 years (1993-2011) from the Wisconsin Longitudinal Study (baseline mean age = 53 years). Depressive symptomatology was measured using the Center for Epidemiologic Studies Depression scale. Cerebrovascular burden was operationalized as hypertension, high blood sugar or diabetes, and other heart problems. APOE genotyping was completed using saliva samples. Hypotheses were examined via a moderated path model and binary logistic regression.

Results: Results supported the hypothesized path model (root mean square error of approximation = 0.041; comparative fit index = 0.959); however, APOE-conferred risk was not a significant moderator of the 2004 or 2011 vascular depression effect and only approached significance as a predictor of depression in 2011 (P = .079). The logistic regression yielded APOE as a significant predictor of clinically significant depressive symptoms in 2011 (P = .02, Exp(B) = 1.197).

Conclusions: The present findings suggest that APOE may influence expression of depressive symptomatology as adults age into and beyond their mid-70s but do not indicate APOE as a moderator of vascular depression. Results posit a potential explanation for inconsistent past findings.