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Peer-reviewedCC BY-NC-NDJAMA Network Open

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

9 affiliations
  1. 1Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
  2. 2Departments of Anatomy & Neurobiology, Chobanian & Avedisian School of Medicine, Boston, Massachusetts
  3. 3Boston University Alzheimer’s Disease Research Center and CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
  4. 4Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
  5. 5Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
  6. 6Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts
  7. 7Department of Neurosurgery, Chobanian & Avedisian School of Medicine, Boston, Massachusetts
  8. 8Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, Massachusetts
  9. 9Concussion & CTE Foundation, Boston, Massachusetts

Abstract

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.

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BibTeX
@article{gallini2026biasadjusted,
  title = {{Bias-Adjusted Prevalence of Chronic Traumatic Encephalopathy Among Deceased National Football League Players}},
  author = {Julia Gallini and Michael L. Alosco and Bobak Abdolmohammadi and Jennifer Weuve and Ann C. McKee and Thor D. Stein and Robert A. Stern and Daniel H. Daneshvar and Jesse Mez and Christopher Nowinski and Yorghos Tripodis},
  journal = {JAMA Network Open},
  year = {2026},
  month = oct,
  doi = {10.1001/jamanetworkopen.2026.40884},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855918},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Bias-Adjusted Prevalence of Chronic Traumatic Encephalopathy Among Deceased National Football League Players
AU  - Julia Gallini
AU  - Michael L. Alosco
AU  - Bobak Abdolmohammadi
AU  - Jennifer Weuve
AU  - Ann C. McKee
AU  - Thor D. Stein
AU  - Robert A. Stern
AU  - Daniel H. Daneshvar
AU  - Jesse Mez
AU  - Christopher Nowinski
AU  - Yorghos Tripodis
PY  - 2026
DA  - 2026/10/01
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.40884
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855918
AB  - 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.
SN  - 2574-3805
ER  -