The effects of repetitive head impacts in former contact sport athletes: an examination of long-term health outcomes and a novel pattern of white matter hyperintensities
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Abstract
Repetitive head impacts (RHI) or recurrent hits and blows the head are the primary risk factor for developing chronic traumatic encephalopathy. However, the clinical manifestations and symptoms are not all explained by tau pathology in chronic traumatic encephalopathy (CTE). Exposure to RHI is associated with a host of other pathologies including white matter and vascular injury. This dissertation will specifically focus on long-term health outcomes associated with playing collegiate level contact and collision sports and neuroimaging metrics of white matter damage similarly associated with RHI exposure from contact and collision sports. The first study aims to examine the association between long term health outcomes and RHI from playing contact and collisions sports. We evaluated health outcomes in a diverse group of National Collegiate Athletic Association (NCAA) Division I athletes from Kent State University (KSU) in Kent, Ohio, including men and women, both contact and collision sport athletes along with non- or- limited contact sport athletes. All participants completed a health history questionnaire of demographics, sports history, current physical and mental health, as well as neuropsychiatric and cognitive complaints.
The second study aims to empirically test the hypothesis that RHI is associated with a distinct pattern of white matter hyperintensities (RHI-WMH) seen on T2 weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). RHI-WMH are visualized as small, punctate lesions at the depths of the sulci near the gray/white matter boundary. We created a novel visual rating system to evaluate FLAIR MRI scans to detect these unique features of WMH specific to RHI i.e., size, sphericity, volume, distance to the gray matter. We conducted these analyses in two distinct cohorts: (1) The Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE Research Project (DxCTE) cohort and (2) the Boston University Alzheimer’s Disease Research Center (BU ADRC) Clinical Core Cohort. The DxCTE cohort permitted comparisons of visual ratings of RHI-WMH between former elite American football players and asymptomatic men. In contrast, the BU ADRC Clinical Core cohort allowed for comparisons between participants with diverse sources of RHI and those without RHI who spanned the cognitive continuum. In the DxCTE sample, we examined plasma biomarkers and 18F-flortaucipir positron emission tomography (PET) correlates of RHI-WMH in former American football players. Finally, we examined the neuropathological correlates of RHI-WMH using ex vivo MRI and histopathological staining of tissue from two deceased American football players who donated their brain and had an antemortem MRI available.
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2025