Cumulative burden of mild TBI in Veterans: Accelerated age-related regional white matter deterioration along major white matter pathways.

Veterans experience mild traumatic brain injury (mTBI) at significantly higher rates than civilians, alongside high rates of comorbid conditions such as PTSD, mood disorders, and alcohol abuse. These conditions have documented impacts on brain health that compound with age. Prior work has demonstrated reduced white matter (WM) integrity and greater age-related trends in WM deterioration in Veterans with mTBI compared to Veterans without mTBI. These studies provide important insights, yet were limited in their ability to differentiate mTBI effects from those of common comorbid conditions. It remains unclear whether specific WM tracts are more vulnerable to mTBI overall or if effects are limited to specific portions of tracts. This study assessed the impact of cumulative mTBI burden on WM aging in U.S. Veterans [n = 710, ages = 19-80, mean age = 37]. Associations between age, mTBI burden, and WM integrity measured via fractional anisotropy, and mean, axial, and radial diffusivity were analyzed using multivariate regression of whole-tract means and along-tract effect clustering via Freesurfer's TRACULA package. Whole-tract interactions by mTBI on age-related deterioration were found in the ventral cingulate bundle and optic radiation. Along-tract analysis identified interactions clusters along these and five additional tracts. In all cases, higher mTBI burden was associated with steeper cross-sectional relationships between age and microstructural integrity. mTBI differentially impacted specific sections of affected WM tracts. These results suggest greater age-related WM deterioration with higher mTBI burden after acute injury recovery extending into later age.