The Contribution of Repetitive Head Impacts and Social Determinants of Health to Alzheimer's Disease and Related Dementia in Older Adult Black Men

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ABSTRACT. Black Americans face nearly double the risk of Alzheimer’s disease (AD) and related compared to Whites. Black American men may be at increased risk for late-life neurological disorders associated with exposure to repetitive head impacts (RHI) and traumatic brain injury (TBI) from contact sports participation and other risk factors. Exposure to RHI/TBI is linked with late-life cognitive impairment, neuropsychiatric disturbances, and structural brain changes. Black racial identity and exposure to RHI/TBI has been shown to have an additive effect on MRI metrics of atrophy and cerebrospinal fluid neurodegenerative disease proteins. These neurological disparities might be explained by social determinants of health (SDOH) (e.g., education access and quality, health care access and quality, neighborhood environment), which might affect resistance and resilience to other neurological disorders from RHI/TBI. SDOH factors might indeed contribute to neurological outcomes in adult Black men irrespective of RHI/TBI. Yet, there has been persistent under- representation of Blacks in biomedical and health research, including among studies of the late effects of RHI from American football play. The overarching goal of this study is to examine the impact of RHI/TBI from American football and the contribution of early-life SDOH to later-life cognitive function, neuropsychiatric symptoms, structural MRI features, and plasma biomarkers in Black male former American football athletes and non-RHI/TBI exposed Black men. We will recruit 100 Black male former American football athletes (across all levels of play and cognitive continuum, 50+ years) and 100 age-matched Black males without RHI/TBI. Participants will enroll to complete harmonized cognitive and neuropsychiatric tests, MRI, and blood draw to assess neurodegenerative disease proteins. A battery of questionnaires (e.g., Adverse Childhood Experiences, Childhood-Experiences Survey, SHARELIFE survey) will be administered to assess SDOH. In Aim 1, we will investigate the association between RHI/TBI and later-life cognitive and neuropsychiatric symptoms in Black male former American football athletes. Aim 2 will investigate the association between RHI/TBI and later-life biomarkers of Aß, p-tau, and neurodegeneration outcomes in Black male former American football athletes. Aim 3 will examine the contribution of SDOH to later-life cognitive and neuropsychiatric symptoms and later-life biomarkers of Aß, p-tau, and neurodegeneration outcomes. Our hypotheses are that (1) RHI/TBI will be associated with worse cognitive and neuropsychiatric function and compromised structural gray/white matter in Black former football players; (2) impoverished SDOH will increase risk and reduce resilience to the late-life effects of RHI/TBI; and (3) impoverished SDOH will mediate the effects of RHI on late-life neurological outcomes. This R01 will discover the role of RHI/TBI and SDOH in older Black men. We will address racial disparities present in data on late life neurological outcomes from RHI/TBI to facilitate accurate disease detection and diagnosis at the individual-level.