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,  = 627), Baltimore Longitudinal Study of Aging (BLSA,  = 684), and Vanderbilt Memory & Aging Project (VMAP,  = 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 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 () ε4 carrier status, and 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: 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10192723PMC
http://dx.doi.org/10.1002/dad2.12425DOI Listing

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