Moderate‐Severe Traumatic Brain Injury History and Chronic Traumatic Encephalopathy Neuropathology in Brain Donors Exposed to Repetitive Head Impacts

Background Repetitive head impacts (RHI) from American football and other sources are associated with the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). Moderate‐to‐severe traumatic brain injury (msTBI) has been suggested to be sufficient to precipitate CTE. Yet, this evidence is based on small case series of msTBI and the interplay between msTBI and RHI on CTE risk is unknown. We modeled the associations between msTBI history and years of American football play (proxy for RHI exposure duration) on CTE neuropathology among deceased American football players. Methods The sample included 471 deceased male football players from the UNITE brain bank, all 40+ years old. Informants of donors were administered the Ohio State University TBI Identification Method to assess TBI history. Loss of consciousness (LOC) for 30+ minutes defined msTBI. CTE was neuropathologically diagnosed and staged using published criteria. Outcomes included CTE status, CTE severity (low vs high), and cumulative p‐tau burden—summary of semi‐quantitative ratings of p‐tau severity across 11 brain regions (n = 402). Binary or linear regressions tested the association between msTBI and each outcome, controlling for age and years of football. A years of play x msTBI history interaction term was examined. Results Tables 1‐2 shows sample characteristics (mean age = 67.89, SD = 12.70; 15.7% Black). Of the sample, 114 (24.2%) had a msTBI history. Years since last TBI with LOC was 37.16 (SD = 18.66) years. 344 (73.0%) had autopsy‐confirmed CTE. There was no association between msTBI and CTE status (OR = 1.38, 95% CI = 0.81,2.33, p = 0.24), CTE severity (OR = 0.77, CI = 0.41,1.44, p = 0.41), or cumulative p‐tau burden (beta = ‐1.03, 95% CI = ‐2.77,0.71, p = 0.25). In contrast, years of football play was associated with CTE status (OR = 1.15, 95% CI = 1.10,1.21, p<0.01), CTE severity (OR = 1.14, 95% CI = 1.08,1.21, p<0.01), and cumulative p‐tau burden (beta = 0.44, 95% CI = 0.32,0.56, p<0.01). There were no years of play x msTBI interaction effects (ps>0.05). Conclusions msTBI history was not associated with CTE neuropathology, nor did it modify the effect of years of football play on CTE status and severity. These findings argue against msTBI as a contributor to CTE in the setting of RHI. Examination of age at msTBI and msTBI frequency, as well as non‐CTE neuropathological correlates of msTBI are next steps.