In a sub-cohort of women and men with +APOE4, engaging in physical activity was more beneficial to men’s brain aging than women’s. In a sub-cohort of women with those risk factors, higher BMI was associated with less brain aging whereas lower BMI was not. An elastic net regression model found that women with a family history of AD and +APOE4 genotype had more advanced brain aging than their male counterparts. We undertook a cross-sectional study of structural MRIs from 1067 cognitively normal adults across four neuroimaging datasets. Using BAG, we investigated whether there were sex differences in the brain effects of AD risk factors (i.e., family history of AD, and carrying an apolipoprotein E ε4 allele ) in cognitively intact adults as well as the role of modifiable factors in moderating this relationship. Brain Age Gap (BAG) is a concept used increasingly as a measure of brain health BAG is defined as the difference between predicted age (based on structural MRI) and chronological age, with negative values reflecting preserved brain health in the face of aging. Determining the effect of AD risk factors on brain aging in women, compared to men, is critical for understanding whether there are sex differences in the pathways towards AD in cognitively intact but at-risk adults. Emerging evidence suggest that Alzheimer’s Disease (AD) risk factors may differentially contribute to disease trajectory in women than men.
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