Abstract
Although the younger age of first exposure (AFE) to American football has not been associated with neurodegenerative pathology, AFE has been associated with clinical symptoms. However, the literature is mixed. We examined the association between AFE to football and clinical outcomes before and after age 60 at death, to isolate the potential role of decreased neuropathological resilience in older age. This study included 677 deceased male football players who donated their brains to the Understanding Neurologic Injury and Traumatic Encephalopathy Brain Bank. Informants completed modified scales assessing cognition, function, behavior, and neuropsychiatric features with dementia adjudicated through consensus conferences. Regressions tested the association between AFE and dementia, chronic traumatic encephalopathy (CTE) pathology, and each scale, adjusted for multiple testing. Analyses were stratified by age 60, adjusting for age at death, duration of play, and neuropathology. Most donors (mean age = 60.9, standard deviation = 19.8) played college or professional football (n = 509, 76%). CTE was the most prevalent neuropathology (n = 471, 70%). AFE was not associated with neurodegenerative disease pathology. Among those older than 60 at death, younger AFE was associated with cognitive composite score impairment (odds ratio: 0.897, 95% confidence interval [CI]: 0.814-0.988, p = 0.027) and worse cognitive (beta: 0.04, 95% CI: 0.01-0.069, p = 0.009), neurobehavioral (beta: 0.032, 95% CI: 0.002-0.062, p = 0.035), and neuropsychiatric (beta: 0.032, 95% CI: 0.00-0.064, p = 0.048) composite scores. Younger AFE was only associated with worse informant-reported clinical outcomes in older deceased football players, independent of neurodegeneration. Our findings offer a potential explanation for the mixed literature on AFE and clinical outcomes. The effects of AFE may only manifest in older adults when cognitive reserve is depleted, neuropathological resilience is reduced, or age-related vulnerabilities interact with prior head injury exposure, worsening clinical outcomes.