Early-life educational attainment, APOE ε4 alleles, and incident dementia risk in late life.

We examined the interactions between educational attainment and genetic susceptibility on dementia risk among adults over 60 years old. A total of 174,161 participants were free of dementia at baseline. The APOE ε4-related genetic risk was evaluated by the number of APOE ε4 alleles. The overall genetic susceptibility of dementia was evaluated by polygenetic risk score (PRS). Cox proportional hazards models were used to estimate the association between educational attainment and incident dementia. During a median of 8.9 years of follow-up, a total of 1482 incident cases of dementia were documented. After adjustment for covariates, we found that low education attainment was significantly associated with higher dementia risk in the APOE ε4 carriers, and such relation appeared to be stronger with the increasing number of ε4 alleles. In contrast, educational attainment was not associated with dementia risk in non-APOE ε4 carriers (P for multiplicative interaction = 0.006). In addition, we observed that the dementia risk associated with a combination of low educational attainment and high APOE ε4-related genetic risk was more than the addition of the risk associated with each of these factors (P for additive interaction < 0.001). We found similar significant interactions between educational attainment and PRS on both the multiplicative and additive scales on the dementia risk, mainly driven by the APOE genotype. These data indicate that higher educational attainment in early life may attenuate the risk for dementia, particularly among people with high genetic predisposition.