Leveraging longitudinal diffusion MRI data to quantify differences in white matter microstructural decline in normal and abnormal aging

Introduction: 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 Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study of Aging [BLSA], Vanderbilt Memory & Aging Project [VMAP]) were free-water corrected and harmonized. This dataset included 1723 participants (age at baseline: 72.8 ± 8.87 years, 49.5% male) and 4605 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 a 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 were free-water corrected and harmonized.Global effects of white matter decline were seen in normal and abnormal aging.The free-water metric was most vulnerable to abnormal aging.Cingulum free-water was the most vulnerable to abnormal aging.