HJNO Jul/Aug 2026

U.S. HEALTHCARE JOURNALS I  JUL / AUG 2026 27 JAMA NETWORK OPEN ORIGINAL INVESTIGATION / NEUROLOGY and neuropsychiatric outcomes compared with controls and (2) in the entire football cohort there were associations consistent with a dose-response pattern between years of play and highest level played and cogni- tive and neuropsychiatric measures. Find- ings demonstrate associations between multiple RHI proxies and later-life cognitive, mood, and behavioral impairments, thereby advancing the existing literature. 21,22,49-52 Many previous studies examining cogni- tive and neuropsychiatric effects of football play failed to include players across all lev- els of play and well-matched control groups. When controls were included, sample sizes were small, and findings were mixed. One cohort study of men who played 1 season or more of high school football in the 1950s included matched controls and found no significant differences in later-life cognitive and depression-related outcomes between groups. 53 Conversely, another study com- paring neuropsychological and neuroim- aging measures across 34 former NFL play- ers and IQ-matched controls found higher rates of cognitive impairment and depres- sion in the football players. 54 Compared with controls, football players in our study performed worse on computerized cogni- tive tests and had more subjective cognitive concerns. They reported more depressive symptoms, aligning with previous findings tying football play to later-life depression, particularly in former elite players. 24,50,55,56 A longitudinal study of US men found that individuals who reported 1 year or more of football play during adolescence did not dis- play elevated depression risk and suicidality in their middle 30s to early 40s. 57 The associ- ation between football play and depression is uncertain and may vary by age and level and duration of play. Previous literature demonstrated a dose-response relationship between years of football play 58 and level of play 59 and chronic traumatic encephalopathy. How- ever, associations between RHI and clini- cal outcomes have been inconsistent. This is likely due to heterogeneity in RHI opera- tionalization, lack of validated tools for RHI quantification, limited range or variability due to focus on the upper end of exposure (ie, former professional players), selection biases in clinical and neuropathological brain bank studies, and lack of account- ing for confounding individual risk factors (eg, genetics and medical comorbidities). Nonetheless, numerous studies have shown dose-response relationships between RHI exposure and clinical outcomes, including