Education and Cardiovascular Health as Effect Modifiers of APOE ε4 on Dementia: The Atherosclerosis Risk in Communities Study

Abstract Background Both education and cardiovascular risk factors are strongly associated with dementia risk. However, it is not clear whether these associations persist or vary among individuals with high genetic risk for Alzheimer’s disease. We examined the interactive relationship between lifestyle and genetic dementia risk factors in a prospective cohort study. Methods Our data came from the Atherosclerosis Risk in Communities study participants (n = 13 715; baseline age 45–64; 25% Black; 55% female), who were followed for incident dementia from 1987 through 2017. We used Cox proportional hazard models to estimate the risk of dementia (ascertained through in-person examination, telephone cognitive screeners, and/or hospital and death records) associated with baseline education and cardiovascular risk factors (measured using the American Heart Association’s “Life Simple 7”) among ε4 carriers and non-carriers separately. We also examined differences by race and sex. Results Two thousand two hundred and twenty-six incident dementia cases occurred over a median 25 years of follow-up. Lower educational attainment and poorer cardiovascular health were associated with greater risk of incident dementia. There was an education by apolipoprotein E (APOE) status interaction (p = .005) whereby the association of education and dementia was weaker for ε4 carriers (HR college graduates vs less than high school: 0.71 [0.59–0.84] than non-carriers (0.54 [0.47–0.63]). There was no interaction between APOE status and cardiovascular health on dementia risk. These relationships did not vary significantly by race or sex. Conclusions Education and cardiovascular health were associated with lower dementia risk regardless of APOE genotype, though the protective effects of education were somewhat diminished among ε4 carriers.