This anticipation effect was most apparent in the offspring of 2 affected parents, which is consistent with prior findings in first-degree relatives of individuals with late-onset AD.1,2,4,7,8 Beyond parental inheritance, more years of education and retrospective reporting of AAO were also associated with an earlier-than-expected intergenerational difference in AAO, while APOE ε4 heterozygosity, family history of early-onset dementia, and late-life hypertension were associated with later-than-expected intergenerational difference in AAO. This evidence concerns the gene APOE and hypertensive disorder.