Characterizing white matter and vascular pathologies in brain donors exposed to repetitive head impacts.

Chronic traumatic encephalopathy (CTE) is a progressive brain disease linked to repetitive head impacts (RHI), often incurred from contact sports, and can lead to dementia. Here, we investigated the association between RHI and white matter/vascular neuropathologies and their relative contribution to dementia status in deceased men 50 + years old with and without exposure to RHI from various types of contact and collision sports. Our sample included two RHI groups from the UNITE brain bank: (1) American Football players (RHI-AF, n = 79), and (2) non-AF contact and collision sport athletes (e.g., boxing, rugby; RHI-CCS, n = 49). Controls included similarly aged (± 5 years) male brain donors without RHI. A modified ischemic injury scale (mIIS) served as a global measure of white matter and vascular neuropathologies, encompassing nine subcomponents. Dementia was determined through diagnostic consensus conference based on interviews with families. Using linear regression models controlling for age at death, mIIS was different in RHI-AF versus non-RHI only (p = 0.036). Subsequent logistic regression of each mIIS subcomponent, controlling for age at death, demonstrated that worse white matter rarefaction (RHI-AF; Beta = 1.42, [95% CI 2.03-8.43]; RHI-CCS; Beta = 1.93, [95% CI 2.35-20.17]) and hippocampal sclerosis (RHI-AF; Beta = 2.01, [95% CI 2.69-20.81]; RHI-CCS; Beta = 2.19, [95% CI 2.49-32.10]) was more common in RHI groups from their controls. Further, logistic regressions found that higher global mIIS correlated with increased odds of dementia in only the RHI-AF group (p = 0.02), driven by white matter rarefaction (β = 0.94, [95% CI 1.66-4.00]) and hippocampal sclerosis (β = 1.08, [95% CI 1.35-6.42]). There were similar findings in RHI-CCS group for odds of dementia (p = 0.048), including white matter rarefaction (β = 0.68, [95% CI 1.22-3.21], p = 0.05). Overall, these results demonstrate that white matter  rarefaction and hippocampal sclerosis are linked to RHI exposure across all types of contact sports. Further, these pathologies contribute to dementia independent of p-tau pathology in American football players.