Aging of gray matter microstructure: A brain-wide characterization of age group differences using NODDI

This study aimed to provide a complete characterization of age group differences in cortical lobar, hippocampal, and subcortical gray matter microstructure using a multi-compartment diffusion-weighted MRI (DWI) approach with parameters optimized for gray matter (Neurite Orientation Dispersion and Density Imaging, NODDI). 76 younger (undergraduate students) and 64 older (surrounding communities) adults underwent diffusion-, T1-, and susceptibility-weighted MRI. Results revealed eight unique patterns across the 12 regions of interest in the relative direction and magnitude of age effects across NODDI metrics, which were grouped into three prominent patterns: cortical gray matter had predominantly higher free diffusion in older than younger adults, the hippocampus and amygdala had predominantly higher dispersion of diffusion and intracellular diffusion in older than younger adults, and the putamen and globus pallidus had lower dispersion of diffusion in older than younger adults. Results remained largely unchanged after controlling for normalized regional volume, suggesting that higher free diffusion in older than younger adults in cortical gray matter was not driven by macrostructural atrophy. Results also remained largely unchanged after controlling for iron content (QSM, R₂*), even in iron-rich subcortical regions. Taken together, these patterns of age effects across NODDI metrics provide evidence of region-specific neurobiological substrates of aging of gray matter microstructure.