Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease

INTRODUCTION The effects of sex and apolipoprotein E ( APOE )—Alzheimer's disease (AD) risk factors—on white matter microstructure are not well characterized. METHODS Diffusion magnetic resonance imaging data from nine well‐established longitudinal cohorts of aging were free water (FW)–corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW‐corrected fractional anisotropy (FA FWcorr ) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status. RESULTS Sex differences in FA FWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION There are prominent differences in white matter microstructure by sex and APOE ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted. Highlights Sex and apolipoprotein E ( APOE ) ε4 carrier status relate to white matter microstructural integrity. Females generally have lower free water–corrected fractional anisotropy compared to males. APOE ε4 carriers tended to have higher free water than non‐carriers.