APOE and Alzheimer disease: In addition to sex differences in associations between CMRs and brain health across different life phases, the risk of neurodegeneration conferred by the APOE4+ genotype is also known to differ between males and females5,18 and may interact with markers of cardiometabolic health.19 For example, in our previous work using the North American PREVENT-AD cohort of cognitively normal participants, we observed that the presence of a family history of AD and the APOE4+ genetic risk was associated with older brain age in females than in males with similar risk levels.