Bias-Adjusted Prevalence of Chronic Traumatic Encephalopathy Among Deceased National Football League Players

Importance: The majority of knowledge regarding chronic traumatic encephalopathy (CTE) in National Football League (NFL) players is derived from autopsy-based studies on voluntarily donated brains. Because these cohorts are highly vulnerable to selection bias (specifically registry bias), population-level prevalence of CTE among former NFL players is unknown, limiting understanding of the impact of this disease. Objective: To estimate the selection-bias adjusted prevalence of CTE neuropathology in deceased NFL players. Design, Setting, and Participants: This population-based cross-sectional study used Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) brain bank data combined with National Death Index records on former NFL players. Both brain donor and nondonor NFL players who died between January 2008 and December 2023 were included. Data were analyzed from November 2025 to April 2026. Exposure: Playing in at least 1 regular or postseason NFL game. Main Outcomes and Measures: The main outcomes of this study were bias-adjusted prevalence of CTE neuropathology and all-cause dementia among the target population, both of which were measured in donors prior to this study. A cognitive symptom-related brain donation selection ratio (probability of donation given CTE divided by the probability of donation given no CTE) was estimated using Poisson regression and was applied to adjust donor-observed prevalence of CTE neuropathology at death and all-cause dementia during life. The prevalence estimates were adjusted for bias using the estimated selection ratio. Results: The cohort consisted of 2362 deceased former NFL players (mean [SD] years played, 5.1 [3.9]; 971 [41.1%] aged ≥80 years at death), of whom 396 were brain donors and 1966 were nondonors. Of 387 donors, 362 (93.5%) had CTE. The median selection ratio was 4.97 (95% CI, 4.72-5.26). Bias-adjusted population prevalence of CTE at death was 74.5% (95% CI, 69.6%-78.3%), with a conservative lower-bound analysis estimating 63.7% (57.2%-68.9%). Bias-adjusted population prevalence of all-cause dementia history during life was 27.2% (95% CI, 22.6%-31.6%). Conclusions and Relevance: The findings of this cross-sectional study suggest that selection bias materially inflates donor-based prevalence estimates but is unlikely to fully explain the high burden of CTE neuropathology among this population. Further research is required to understand the clinical impact of this disease.