Exercise is associated with reduced risk of depressive symptoms at older ages, while recent work suggests that the apolipoprotein E type 4 allele (APOE-e4) may increase risk. There are no studies of whether APOE-e4 moderates the relationship between exercise and later life depressive symptoms. This study aimed to explore whether the prospective associations between exercise and subsequent depressive symptoms were distinct between APOE-e4 carriers and non-carriers using nationwide data.
Data from 639 participants (mean age = 66.14, SD = 7.26) in 2000 with 6 years of follow-up were studied. Depressive symptoms were assessed using the Center for Epidemiologic Studies–Depression Scale. Exercise and the APOE genotype were also assessed at baseline. Negative binomial regression models were conducted to examine the combined effects of exercise and APOE-e4 status on subsequent depressive symptoms when controlling for baseline depressive symptoms and other covariates. Sensitivity analyses to test for confounding, reverse causality, and attrition were conducted.
Among APOE-e4 carriers, there was no significant difference in depressive symptoms between high active and low active groups. In contrast, high active APOE-e4 non-carriers had fewer depressive symptoms than low active APOE-e4 non-carriers. The beneficial effect of exercise on depressive symptoms is restricted to APOE-e4 non-carriers. Sensitivity analyses provided further support for the robustness of these findings.
This is the first prospective study investigating whether APOE-e4 moderates the association between exercise and depressive symptoms. It proposes that genetic variation in APOE may influence the effect of exercise on depressive symptoms.