Education Moderates the Negative Effect of Apolipoprotein E ε4 on Response Inhibition in Older Adults

Background: Studies have reported that apolipoprotein E epsilon 4 (APOE epsilon 4) 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 epsilon 4 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 epsilon 4 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 genotypewas observed across the four EF components, the potentially adverse effects of epsilon 4 on inhibition were alleviated by high educational attainment. Amain 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 epsilon 4 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.

Automated summary

This study investigated the impact of APOE ε4 on executive functions in late adulthood, finding that high educational attainment can mitigate the negative effects of ε4 on inhibition, and education has a main effect on the reasoning component.