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

Abstract

Structured AbstractINTRODUCTIONThe effects of sex, race, and Apolipoprotein E (APOE) – Alzheimer’s disease (AD) risk factors – on white matter integrity are not well characterized.METHODSDiffusion 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 (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, andAPOE-ε4 carrier status.RESULTSSex differences in FAFWcorrin association and projection tracts, racial differences in FAFWcorrin projection tracts, andAPOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.DISCUSSIONThere are prominent differences in white matter microstructure by sex, race, andAPOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.HighlightsSex, race, andAPOE-ε4 carrier status relate to white matter microstructural integrityFemales generally have lower FAFWcorrcompared to malesNon-Hispanic Black adults generally have lower FAFWcorrthan non-Hispanic White adultsAPOE-ε4 carriers tended to have higher FW than non-carriersResearch in ContextSystematic ReviewThe authors used PubMed and Google Scholar to review literature that used conventional and free-water (FW)-corrected microstructural metrics to evaluate sex, race, andAPOE-ε4 differences in white matter microstructure. While studies have previously explored differences by sex andAPOE-ε4 status, less is known about racial differences and no large-scale FW-corrected analysis has been performed.InterpretationSex and race were more associated with FAFWcorrwhileAPOE-ε4 status was associated with FW metrics. Association, projection, limbic, and occipital transcallosal tracts showed the greatest differences.Future DirectionFuture studies to determine the biological and social pathways that lead to sex, racial, andAPOE-ε4 differences are warranted.Consent StatementAll participants provided informed consent in their respective cohort studies.