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

Introduction: The effects of sex, race, and Apolipoprotein E ( APOE ) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized.
Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FA _FWcorr ) were used to assess differences in white matter microstructure by sex, race, and APOE -ε4 carrier status.
Results: Sex differences in FA _FWcorr in association and projection tracts, racial 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, race, 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.
Competing Interests: SCJ has served on advisory boards for Enigma Biomedical and ALZPath in the past two years. AJS receives support from multiple NIH grants (P30 AG010133, P30 AG072976, R01 AG019771, R01 AG057739, U19 AG024904, R01 LM013463, R01 AG068193, T32 AG071444, U01 AG068057, U01 AG072177, U19 AG074879, and U24 AG074855). He has also received support from Avid Radiopharmaceuticals, a subsidiary of Eli Lilly (in kind contribution of PET tracer precursor) and participated in Scientific Advisory Boards (Bayer Oncology, Eisai, Novo Nordisk, and Siemens Medical Solutions USA, Inc) and an Observational Study Monitoring Board (MESA, NIH NHLBI), as well as External Advisory Committees for multiple NIA grants. He also serves as Editor-in-Chief of Brain Imaging and Behavior, a Springer-Nature Journal.