Archer, Derek B.Schilling, KurtShashikumar, NiranjanaJasodanand, VarunaMoore, Elizabeth E.Pechman, Kimberly R.Bilgel, MuratBeason-Held, Lori L.An, YangShafer, AndreaFerrucci, LuigiRisacher, Shannon L.Gifford, Katherine A.Landman, Bennett A.Jefferson, Angela L.Saykin, Andrew J.Resnick, Susan M.Hohman, Timothy J.Alzheimer’s Disease Neuroimaging Initiative2024-01-252024-01-252023-05-18Archer DB, Schilling K, Shashikumar N, et al. Leveraging longitudinal diffusion MRI data to quantify differences in white matter microstructural decline in normal and abnormal aging. Preprint. bioRxiv. 2023;2023.05.17.541182. Published 2023 May 18. doi:10.1101/2023.05.17.541182https://hdl.handle.net/1805/38182Introduction: It is unclear how rates of white matter microstructural decline differ between normal aging and abnormal aging. Methods: Diffusion MRI data from several well-established longitudinal cohorts of aging [Alzheimer's Neuroimaging Initiative (ADNI), Baltimore Longitudinal Study of Aging (BLSA), Vanderbilt Memory & Aging Project (VMAP)] was free-water corrected and harmonized. This dataset included 1,723 participants (age at baseline: 72.8±8.87 years, 49.5% male) and 4,605 imaging sessions (follow-up time: 2.97±2.09 years, follow-up range: 1-13 years, mean number of visits: 4.42±1.98). Differences in white matter microstructural decline in normal and abnormal agers was assessed. Results: While we found global decline in white matter in normal/abnormal aging, we found that several white matter tracts (e.g., cingulum bundle) were vulnerable to abnormal aging. Conclusions: There is a prevalent role of white matter microstructural decline in aging, and future large-scale studies in this area may further refine our understanding of the underlying neurodegenerative processes. Highlights: Longitudinal data was free-water corrected and harmonizedGlobal effects of white matter decline were seen in normal and abnormal agingThe free-water metric was most vulnerable to abnormal agingCingulum free-water was the most vulnerable to abnormal aging.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalWhite matterDiffusion MRIHarmonizationFree-waterAgingArticle