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

Abstract

IntroductionIt is unclear how rates of white matter microstructural decline differ between normal aging and abnormal aging.MethodsDiffusion 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.ResultsWhile 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.ConclusionsThere 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.

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

“…11 Previous work has consistently found that association tracts are affected in the aging process 10,28 and these tracts show a greater decline in FA and FAFWcorr in individuals with cognitive impairment relative to cognitively unimpaired adults. 28,53 While some studies have shown that projection fibers are also associated with abnormal cognitive aging, these associations are less robust. 10,28,49 Given that females are disproportionately affected by AD, the observed sex differences in FAFWcorr in our study suggest that white matter integrity may contribute to this disparity.…”

“…Consistent with prior work, 28,[48][49][50][51] we used freely accessible tractography templates (https://github.com/VUMC-VMAC/Tractography_Templates) to assess the white matter microstructure in our cohort (Figure 1). In total, we used 48 tract templates from seven different tract types, including association, limbic, projection, motor transcallosal, occipital transcallosal, parietal transcallosal, and prefrontal transcallosal areas.…”

“…Importantly, FW metrics are considered more sensitive to abnormal brain aging. [28][29][30] While previous studies have found loss of white matter integrity in limbic, association, and transcallosal (TC) tracts 28,29,[31][32][33][34][35] associated with cognitive impairment and AD, there has yet to be a large-scale analysis leveraging FW measures to understand how sex, race, and APOE-ε4 carrier status are associated with longitudinal white matter integrity.…”

Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia

“…16,[23][24][25] Microstructural decline of WM and GM is a common finding in neurodegenerative conditions, including AD, 26 Parkinson's disease, 15 and aging. 27 Increased FW of widespread WM tracts has been reported in mild cognitive impairment (MCI) and AD compared to control brains. [28][29][30] Increased FW and decreased FAt values in medial temporal WM tracts at baseline were found to associate with more rapid longitudinal cognitive decline.…”

“…Microstructural decline of WM and GM is a common finding in neurodegenerative conditions, including AD, 26 Parkinson's disease, 15 and aging 27 . Increased FW of widespread WM tracts has been reported in mild cognitive impairment (MCI) and AD compared to control brains 28–30 .…”