HJNO Jul/Aug 2026

U.S. HEALTHCARE JOURNALS I  JUL / AUG 2026 21 INTRODUCTION Repetitive head impacts (RHI) incurred through American football play can result in symptomatic and asymptomatic trau- matic brain injuries (TBI). 1,2 Autopsy studies demonstrate that cumulative RHI exposure from American football can confer risk of the neurodegenerative disease chronic trau- matic encephalopathy, 3-6 alongside related neurodegenerative conditions 7-11 and other neuropathological conditions (eg, white matter degeneration). 12 In vivo neuroim- aging studies of living former American football players similarly show evidence of structural, 13-16 functional, 17,18 and molecu- lar 19,20 brain changes. Studies 21-27 have found associations between higher football exposure, as indexed by proxies (eg, age of first exposure and total years of play), and later-life cog- nitive and neuropsychiatric function (eg, depression, apathy, and neurobehavioral changes). Literature 5,28-31 is inconsistent on the presence, type, and severity of clini- cal symptoms, in addition to uncertainty regarding their association with RHI. These inconsistencies could partially stem from methodological differences, including var- ied definitions of RHI exposure. 25 Exposed groups in most studies 32-34 have consisted of small samples of elite football players at the exclusion of individuals who played at high school and youth levels. Use of adequately comparable, non–football-playing control groups has also been uncommon. Long- term cognitive and neuropsychiatric effects of RHI exposure from American football remain poorly understood, particularly in terms of how observed associations gener- alize to all football players. We examined cross-sectional associa- tion of priorAmerican football participation across all levels of play (youth, high school, college, and professional) with cognitive and neuropsychiatric function, leveraging a cohort of former American football players 40 years or older. Two substudies comprised this investigation. In the first, we evaluated differences in cognitive and neuropsychi- atric outcomes between a subset of the for- mer American football players and a demo- graphically well-matched group of men not exposed to RHI. In the second substudy, we used data solely from the football player cohort to evaluate RHI exposure proxies (years of play, age of first exposure, high- est level of play, and position) associated ABSTRACT Importance Repetitive head impacts (RHI) from American football have been associated with later-life cognitive and neuropsychiatric changes. Findings have been limited by small samples, focus on elite players, and lack of appropriate control groups. Objective To assess the association between American football participation and cognitive and neuropsychiatric function in men 40 years or older. Design, Setting, and Participants In this cross-sectional study, online data from male football players in the Head Impact & Trauma Surveillance Study (HITSS) were collected between March 7, 2022, andApril 9, 2025. In a subanalysis, football players were matched to Brain Health Registry controls without RHI. Exposure RHI proxies, including self-reported total years of football play, highest level of play, position, and age of first exposure. Main Outcomes and Measures Linear regression models with multiway cluster-robust SEs compared performance of players vs controls on computerized cognitive tests (Cambridge Automated Neuropsychological Battery Paired Associates Learning Test First Attempt Memory Score [PALFAMS] and Total Errors Adjusted [PALTEA]), subjective cognitive concerns (Everyday Cognition Scale [ECog]), and depressive symptoms (Geriatric Depression Scale 15 [GDS-15]). Multivariable linear regressions, analyses of covariance, and binary logistic regression models tested associations between RHI proxies and PALFAMS, PALTEA, ECog, GDS-15, and additional neuropsychiatric (Behavior Rating Inventory of Executive Function–Adult [BRIEF-A] Behavioral Regulation Index [BRI]) and cognitive (BRIEF-A Meta-Cognition Index [MI]) measures. Models were adjusted for age, race, educational level, and vascular risk. Results The study sample included 3970male former American football players (mean [SD] age, 55.93 [10.00] years) enrolled in HITSS. Two substudies were performed: (1) all 3970 football players and (2) 943 players and controls (mean [SD] age, 58.46 [10.37] years), including 661 football players and 282 BrainHealth Registry controls. Overall, all study participants were highly educated (561 [85%] had a ≥4-year degree). Compared with controls, players had worse scores on PALFAMS (B=−0.64; 95% CI, −1.23 to 0.05; β β=−0.15; P=.03), PALTEA (B=0.31; 95% CI, 0.07-0.54; β =0.18; P=.01), ECog (B=0.11; 95% CI, 0.07-0.15; β =0.38; P<.001), and GDS-15 (B=0.62; 95% CI, 0.39-0.86; β =0.37; P<.001). Among the 3970 total players (mean [SD] years of education, 16.11 [2.20]), professional players had worse scores than college and high school or youth players. Years of play was associated with higher ECog (B=0.006; 95%CI, 0.003-0.009; adjusted P <.001), MI (B=0.17; 95% CI, 0.02-0.32; adjusted P =.04), BRI (B=0.27; 95% CI, 0.16-0.37; adjusted P <.001), GDS-15 (B=0.03; 95% CI, 0.009-0.04; adjusted P =.003), and PALTEA (B=0.03; 95%CI, 0.004-0.06; adjusted P =.04) scores. Conclusions and Relevance In this cross-sectional study of former American football players, prior American football participation was associated with worse later-life cognitive and neuropsychiatric function. These findings support a dose-response association with years and level of play, providing context to help clinicians and researchers assess the risk of symptoms among former players. Cognitive and Neuropsychiatric Function in Former American Football Players Aaronson A, Badlam G, Mulayi SC, et al. Cognitive and Neuropsychiatric Function in Former American Football Players. JAMA Netw Open . 2026;9(2):e2560077. doi:10.1001/jamanetworkopen.2025.60077 © 2026 LLS. Printed with permission. https://creativecommons.org/licenses/by/4.0/ JAMA NETWORK OPEN ORIGINAL INVESTIGATION / NEUROLOGY