Mapping the aging brain: Insights into microstructural changes from free water-corrected fractional anisotropy

Aging has a significant impact on brain structure, demonstrated by numerous MRI studies using diffusion tensor imaging (DTI). While these studies reveal changes in fractional anisotropy (FA) across different brain regions, they tend to focus on white matter tracts and cognitive regions, often overlooking gray matter and motor areas. Additionally, traditional DTI metrics can be affected by partial volume effects. To address these limitations and gain a better understanding of microstructural changes across the whole brain, we utilized free water-corrected fractional anisotropy (FAt) to examine aging-related microstructural changes in a group of 20 young adults (YA) and 24 older adults (OA). A voxel-wise analysis revealed that YA had higher FAt values predominantly in white matter tracts associated with both motor and non-motor functions. In contrast, OA showed higher levels of FAt primarily in gray matter regions, including both subcortical and cortical motor areas, and occipital and temporal cortices. Complementing these cross-sectional results, correlation analyses within the OA group showed that many of these changes are further exacerbated with increasing age, underscoring the progressive nature of these microstructural alterations. In summary, the distinct patterns of FAt changes in gray versus white matter with aging suggest different underlying mechanisms. While white matter FAt values decrease, likely due to axonal degeneration, the increase in gray matter FAt could reflect either compensatory processes or pathological changes. Including behavioral data in future studies will be crucial for understanding the functional implications of these microstructural gray matter changes and their effects on cognitive and motor functions.