Introduction: White matter microstructure may be abnormal along the Alzheimer's disease (AD) continuum.
Methods: Diffusion magnetic resonance imaging (dMRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 627), Baltimore Longitudinal Study of Aging (BLSA, n = 684), and Vanderbilt Memory & Aging Project (VMAP, n = 296) cohorts were free-water (FW) corrected and conventional, and FW-corrected microstructural metrics were quantified within 48 white matter tracts. Microstructural values were subsequently harmonized using the Longitudinal ComBat technique and inputted as independent variables to predict diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI], AD). Models were adjusted for age, sex, race/ethnicity, education, apolipoprotein E (APOE) ε4 carrier status, and APOE ε2 carrier status.
Results: Conventional dMRI metrics were associated globally with diagnostic status; following FW correction, the FW metric itself exhibited global associations with diagnostic status, but intracellular metric associations were diminished.
Discussion: White matter microstructure is altered along the AD continuum. FW correction may provide further understanding of the white matter neurodegenerative process in AD.
Highlights: Longitudinal ComBat successfully harmonized large-scale diffusion magnetic resonance imaging (dMRI) metrics.Conventional dMRI metrics were globally sensitive to diagnostic status.Free-water (FW) correction mitigated intracellular associations with diagnostic status.The FW metric itself was globally sensitive to diagnostic status. Multivariate conventional and FW-corrected models may provide complementary information.
Keywords: diagnosis; diffusion MRI; free‐water; harmonization; white matter.
© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.