Assessing for interaction between APOE epsilon 4, sex, and lifestyle on cognitive abilities

Objective To test for interactions between APOE epsilon 4 genotype and lifestyle factors on worse cognitive abilities in UK Biobank. Methods Using UK Biobank cohort data, we tested for interactions between APOE epsilon 4 allele presence, lifestyle factors of alcohol intake, smoking, total physical activity and obesity, and sex, on cognitive tests of reasoning, information processing speed, and executive function (n range = 70,988-324,725 depending on the test). We statistically adjusted for potential confounders of age, sex, deprivation, cardiometabolic conditions, and educational attainment. Results There were significant associations between APOE epsilon 4 and worse cognitive abilities, independent of potential confounders, and between lifestyle risk factors and worse cognitive abilities; however, there were no interactions at multiple correction-adjusted p < 0.05, against our hypotheses. Conclusions Our results do not provide support for the idea that e4 genotype increases vulnerability to the negative effects of lifestyle risk factors on cognitive ability, but rather support a primarily outright association between APOE epsilon 4 genotype and worse cognitive ability.