Normal-appearing cerebral white matter in healthy adults: mean change over 2 years and individual differences in change

Diffusion tensor imaging studies show age-related differences in cerebral white matter (WM). However, few have studied WM changes over time, and none evaluated individual differences in change across a wide age range. Here, we examined 2-year WM change in 96 healthy adults (baseline age, 19-78 years), individual differences in change, and the influence of vascular and metabolic risk thereon. Fractional anisotropy (FA), axial diffusivity, and radial diffusivity (RD) represented microstructural properties of normal-appearing WM within 13 regions. Cross-sectional analyses revealed age-related differences in all WM indices across the regions. In contrast, latent change score analyses showed longitudinal declines in axial diffusivity in association and projection fibers and increases in anterior commissural fibers. FA and RD evidenced a less consistent pattern of change. Metabolic risk mediated the effects of age on FA and RD change in corpus callosum body and dorsal cingulum. These findings underscore the importance of longitudinal studies in evaluating individual differences in change and the role of metabolic factors in shaping trajectories of brain aging.