Education Moderates the Negative Effect of Apolipoprotein E ɛ4 on Response Inhibition in Older Adults

Abstract

Background: Studies have reported that apolipoprotein E epsilon 4 (APOE ɛ4) has adverse effects on executive functions (EFs) in late adulthood. However, the results have been inconsistent. Insufficient measurements of executive functioning, uncontrolled clinical and demographic confounders, and moderation effects from other environmental factors are suspected to account for the inconsistency. Objective: This study used aggregate measures to examine the effects of APOE ɛ4 on four components of EFs, namely switching, working memory, inhibition, and reasoning. We further investigated whether high educational attainment, a proxy measure for cognitive reserve, moderates the adverse effects of ɛ4 on EFs. Methods: Cognitively unimpaired older participants were divided into groups based on APOE genotype and into subgroups based on educational attainment level. The demographic and clinical variables were matched between the groups. Four core components of the EFs were measured using a relatively comprehensive battery. Results: The results revealed that although no main effect of the APOE genotype was observed across the four EF components, the potentially adverse effects of ɛ4 on inhibition were alleviated by high educational attainment. A main effect of education on the reasoning component was also observed. The moderation analysis revealed that for older adults with 12 years of education or fewer, the relationship between the APOE ɛ4 genotype and inhibition performance became increasingly negative. Conclusion: This study highlights the distinctive role of response inhibition in the gene–environment interaction and underlines the importance of considering factors of both nature and nurture to understand the complex process of cognitive aging.