APOE genotype and cognitive decline: educational context as a moderator of genetic risk.

Objectives: The apolipoprotein E (APOE) ε4 allele is linked to increased risk of Alzheimer's disease and cognitive decline. While educational attainment appears to mitigate this risk, it is not a direct measure of the early-life environment. This study examined whether childhood exposure to well- versus poorly resourced educational contexts modified the association between APOE ε4 and cognitive decline, independent of parent and respondent educational attainment.

Methods: We used data from the Health and Retirement Study (2006-2018) linked with state-level data on public education systems. The sample included U.S.-born respondents who participated in the 2006-2012 genetic data collection, lived in one of the 48 contiguous states at age 10, and were born between 1914 and 1959 (n = 14,817 respondents, 76,806 person-period observations). To measure educational context, we created a standardized factor score representing state education resources, derived from indicators such as per-pupil spending, pupil-teacher ratios, and teacher salary. We used mixed effects models to estimate the interaction between APOE ε4 and state education resources, adjusting for parent and respondent education (measured in years of schooling).

Results: APOE ε4 carriers who grew up in states with low education resources experienced an accelerated rate of cognitive decline compared to carriers from states with high education resources. For noncarriers, the rate of cognitive decline was not statistically different across educational contexts.

Discussion: Ensuring access to high-quality education may serve as an effective social policy to slow cognitive decline among future cohorts of older adults at high genetic risk of dementia.