While our focus was on participant sex, gender may further clarify the relationships between CMRs, APOE4 status, and brain age over time.44 Gender-related factors, such as the increased caregiving responsibilities often shouldered by womales, might be linked to higher stress levels and increased risk of hypertension, compounded by other lifestyle and psychosocial challenges.45 Our samples predominantly consisted of White participants from the United Kingdom, restricting the generalizability of our results to more diverse cohorts. This evidence concerns the gene APOE and hypertensive disorder.