Late Pathologies of Exposure to Repetitive Head Impacts from Contact Sports: White Matter and Vascular Contributions to Cognitive Impairment, Dementia, and Neuropsychiatric Symptoms

The project will conduct sophisticated in vivo and ex vivo assessments of white matter (WM) integrity and cerebrovascular disease (CBVD) in living and deceased former contact sport athletes. It will examine risk factors for, and the cognitive and neuropsychiatric effects of, WM degeneration and CBVD. Researchers will recruit 200 former contact sport athletes (>50 years, male and female from different sports) and 100 age- and race-matched controls without RHI or traumatic brain injury (TBI). Participants will undergo cognitive and neuropsychiatric tests, advanced MRI protocols of WM integrity and CBVD, and blood draws for plasma biomarker analysis. A subgroup will undergo lumbar puncture for CSF analysis. The project will also expand an existing U54 study by adding novel ELISA, multiplex immunofluorescence, and CLARITY pathological assessments of WM integrity and CBVD on 200 deceased contact sport athletes and 100 age-/race-matched non-RHI/TBI donors across 7 harmonized brain banks.