Education as a Modifier of Genetic Influence on Cognitive Ability in Older Adults

Whether education modifies genetic influences on cognition has not been fully explored, especially in non-European populations. Using the older adult cohort from the Taiwan Biobank of East Asian populations, this study aimed to investigate the modifying effect of education on the association of the apolipoprotein E (APOE) ε4 allele and polygenic scores (PGS) for Alzheimer's disease (PGS_AD), cognitive performance (PGS_CP), education attainment (PGS_EA), and schizophrenia (PGS_SCZ) with cognitive ability. Participants aged > 60 years were included in this cohort study. The Mini-Mental State Examination (MMSE) was used for cognitive assessment of 27,343 individuals at baseline (mean age: 63.57 years), and follow-up data were available for 6,273 participants. Linear regression models were employed to examine the association between genetic factors and baseline MMSE scores and MMSE decline and further stratified by education to test the modifying effect. The APOE ε4 allele, PGS_AD, PGS_CP, PGS_EA, and PGS_SCZ were associated with baseline MMSE but not MMSE decline. The positive effects of the PGS_CP and PGS_EA on baseline MMSE, and negative effect of the PGS_SCZ on baseline MMSE and MMSE decline were higher for individuals with lower education. This study demonstrated the transferability of European-derived PGSs to older community samples of East Asian populations. Education mitigates specific genetic effects on cognition, which supports and extends cognitive reserve theory. Promoting cognitive health in older adults by extending education is of importance, especially for populations with higher genetic predispositions and lower education attainment.