Sex, Apolipoprotein E 4 Status, and Hippocampal Volume in Mild Cognitive Impairment

Design: This study evaluated MCI in 193 subjects (86 women and 107 men) participating in a multicenter clinical trial, all of whom underwent magnetic resonance imaging at their baseline visit. We evaluated the association among the number of APOE*E4 alleles, memory performance, and hippocampal volume in men and women with tests of means and multiple linear regressions. Results: Compared with MCI subjects with no APOE*E4 alleles, women with 1 or 2 APOE*E4 alleles were found to have significantly reduced hippocampal volume, whereas men only showed a significant reduction in hippocampal volume when carrying 2 APOE*E4 alleles. Worsening of performance on a delayed word recall task (Alzheimer’s Disease Assessment Scale cognitive subscale) showed an identical pattern in association with APOE*E4 allele dose and sex. Furthermore, when controlling for memory performance on delayed word recall, the APOE*E4 effect on hippocampal volumes was attenuated in men, but remained significant in women.