Multishell diffusion imaging reveals sex-specific trajectories of early white matter degeneration in normal aging

During aging, human white matter (WM) is subject to dynamic structural changes which have a deep impact on healthy and pathological evolution of the brain through the lifespan; characterizing this pattern is of key importance for understanding brain development, maturation, and aging as well as for studying its pathological alterations. Diffusion magnetic resonance imaging (MRI) can provide a quantitative assessment of the white-matter microstructural organization that characterizes these trajectories. Here, we use both conventional and advanced diffusion MRI in a cohort of 91 individuals (age range: 13-62 years) to study region- and sex-specific features of WM microstructural integrity in healthy aging. We focus on the age at which microstructural imaging parameters invert their development trend as the time point which marks the onset of microstructural decline in WM. Importantly, our results indicate that age-related brain changes begin earlier in males than females and affect more frontal regions-in accordance with evolutionary theories and numerous evidences across non-MRI domains. Advanced diffusion MRI reveals age-related WM modification patterns which cannot be detected using conventional diffusion tensor imaging.