APOE and Alzheimer disease: One possible mechanism for the effect of gender in AD is the role of sex hormones on brain and cognitive function, apparent in both animal and human studies investigating the role estrogen on risk of dementia and cognition in women (for review, Farrer et al., 1997) as well as the importance of APOE on evaluating estrogen replacement (Kang and Grodstein, 2012, Yaffe et al., 2000).