Abstract
This meta-analysis and systematic review synthesized data from 30 longitudinal diffusion tensor imaging (DTI) studies on the magnitude, direction, spatial patterns, and modifiers of naturally occurring within-person changes in healthy adult white matter (WM) microstructure. Results revealed: (1) significant within-person declines in fractional anisotropy (FA) in the whole WM (d = -0.12), genu (d = -0.16), and splenium (d = -0.13); (2) greater declines in FA associated with older age, longer follow-up times, and female sex; (3) a possible yet inconclusive vulnerability of late-myelinating WM (the "development-to-degeneration" gradient); and (4) factors decelerating (e.g., physical activity and social activities) and accelerating (e.g., vascular risk factors, biomarkers for Alzheimer's disease, and alcohol consumption) age-related FA changes. Our findings encourage the consideration of WM as a new target for treatments and interventions against cognitive decline and lay the foundation for studying the plastic and regenerative potential of adult WM in clinical trials. Individual differences in WM changes could aid in the preclinical diagnosis of dementia, opening a window for earlier, more effective treatments.