Uncovering patterns of white matter degeneration in normal aging: Links between morphometry and microstructure.

While tract-wise differences in volume and microstructure are common targets of investigation in age-related changes in the white matter (WM), there has been relatively little exploration into other attributes of tract morphometry or its relation to microstructure in vivo, and limited understanding on how they jointly inform the understanding of the WM aging trajectory. This study examines 10 WM tracts for tract-wise differences in morphometry (i.e., volume, length, and volume-to-length ratio) and microstructural integrity (i.e., fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity) using diffusion MRI data from the Human Connectome Project in Aging (HCP-A) with the goal of laying the foundation for a more comprehensive model of age-related WM microstructure-morphometry trajectories with a special focus on age-shifted correlations and sex differences. Results indicated that degeneration in microstructure was detectable at younger ages than changes in morphometry, with widely heterogeneous patterns of interrelation and morphometry-microstructural associations in aging both across tracts and between sexes. Multi-parametric signatures of decline suggest differing stages or mechanisms of degeneration across tracts, with female subjects exhibiting a higher proportion of tracts in later stages of decline than males. This work highlights the value of integrating microstructural and morphometric measures of WM health, and encourages the integration of yet more modalities in improving our mechanistic understanding of WM aging.