The presence of the apolipoprotein E4 allele (APOE4) has been associated with an increased risk of Alzheimer's disease (AD). Moreover, APOE4 has been associated with greater hippocampal atrophy in women than in men with AD.
Studies demonstrating this relationship in patients with mild cognitive impairment (MCI), that is considered the prodromal phase for AD, are lacking. Fleisher and coll. evaluated the association among the number of
APOE4 alleles, memory performance, and hippocampal volume in 86 women and
107 men with MCI. Results showed that men with MCI require APOE4 homozygosis to show significant hippocampal volume loss and worsened memory performance, while women are vulnerable to the negative effects of even a single APOE4 allele. The Authors hypothesize that the combined effect of estrogen loss and the presence of the APOE4 genotype might explain the greater AD risk in women carrying the APOE4 allele than in men. Moreover, results of this study point to the need of evaluating differences by sex in future clinical trials using hippocampal volume as surrogate outcome of disease progression.