A major NFL brain study puts new numbers on the burden of CTE

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Aug 26 2026

By tracking every identified former NFL player who died over 14 years and examining hundreds of donated brains, researchers sought to overcome a long-standing challenge in estimating the true burden of CTE.

Study: Prevalence of chronic traumatic encephalopathy at death in National Football League players: retrospective population based cohort study, 2008-21. Image Credit: Steeve Raye / Shutterstock

In a recent study published in The BMJ, researchers conducted a retrospective population-based investigation to evaluate the prevalence of chronic traumatic encephalopathy (CTE) at death and its clinicopathological association with dementia among former National Football League (NFL) players.

Researchers specifically analyzed postmortem neuropathology and National Death Index records from a fully enumerated cohort comprising all 1,712 identified former NFL players who died between 2008 and 2021. Study findings revealed that, under the most conservative epidemiological assumptions, the minimum prevalence of CTE at death was 18.5% across the entire study period, with the minimum reaching 24.5% during 2016–2021, when brain donation was most frequent.

The analysis further found that stage IV CTE was associated with a significantly increased risk of clinician-adjudicated dementia. The study consequently concluded that CTE neuropathology is common at death among former professional football players in this cohort and that greater CTE severity was associated with dementia among brain donors. The authors said the findings could inform future research and policy recommendations while emphasizing that further work is needed to clarify the relationship between CTE and dementia.

Background

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with high exposure to repetitive head impacts (RHIs). The condition is most often observed in contact sports, with previous epidemiological research indicating that people with repetitive head-impact exposure, including former contact sports athletes, face elevated mortality from neurodegenerative conditions (compared to the general population).

However, reviews from the field highlight that quantifying population-level CTE prevalence has remained challenging to date. CTE can currently be definitively diagnosed only by neuropathological examination after death, with a growing body of literature demonstrating that prior investigations relying on convenience brain bank samples have been subject to potential selection and ascertainment biases.

Consequently, researchers lacked an understanding of the true mathematical range of CTE prevalence at death within contact sports-specific cohorts and its association with neurodegenerative conditions such as dementia.

About the study

The present study aimed to address these uncertainties by estimating the possible range of CTE prevalence at death and examining the association between severe CTE pathology and dementia.

The study’s fully enumerated cohort comprised 1,712 former NFL players who died between 2008 and 2021, of whom 338 donated their brains for neuropathological assessment. The sample was restricted in the primary analysis to players who debuted after 1949 (when mandatory plastic helmet use was introduced) and died between 2008 and 2021.

Neuropathological assessments were conducted on 338 donated brains (19.7% of all decedents) through the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) and University of California, San Francisco Alzheimer's Disease Research Center (UCSF ADRC) brain banks, with investigating pathologists masked to donors’ athletic histories and clinical symptoms.

Researchers obtained informant-based clinical histories from brain donors and requested medical records for all cases, receiving records for 184 donors. Clinicians masked to neuropathological status adjudicated dementia diagnoses using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and available records from before death.

The study’s statistical analyses focused on three primary areas: 1. Minimum and maximum CTE prevalence at death across the cohort, 2. Multivariable associations between stage IV CTE and adjudicated dementia using inverse probability weighting (IPW) to adjust for potential bias associated with brain donation, and 3. Comparison of clinician-adjudicated dementia with neurodegenerative disease recorded on official death certificates.

Study findings

Neuropathological examination revealed that 315 of the 338 donated brains (93.2%) investigated demonstrated neuropathologically confirmed CTE. Using extreme assumptions about CTE status among players whose brains were not examined, the researchers calculated that the possible prevalence of CTE at death across all 1,712 decedents in the sample cohort ranged from a conservative minimum of 18.5% to a maximum of 98.7%.

During the 2016–2021 period, when donation rates reached 26.8% (235 of 878 decedents), the minimum possible CTE prevalence was 24.5% (maximum 97.7%). The higher minimum during this period largely reflected the greater proportion of decedents whose brains underwent neuropathological examination rather than evidence that CTE prevalence itself increased over time.

Furthermore, comparison of donors’ CTE status with their clinical records showed that 104 (30.8%) had stage IV CTE, while 202 (59.8%) met clinical criteria for dementia. After accounting for potential differences between brain donors and non-donors, donors with stage IV CTE had a 44% higher risk of dementia than those without stage IV disease, strengthening the evidence for an association between severe CTE pathology and cognitive decline.

Death certificates also substantially undercaptured clinician-adjudicated dementia: only 40.6% of donors with clinician-adjudicated dementia had a neurodegenerative disease recorded as either a primary or secondary cause of death.

Conclusions

The present study indicates that CTE neuropathology was common among deceased former NFL players, with at least one in four of those who died during 2016–2021 having confirmed CTE at death. The association between stage IV CTE and dementia among brain donors supports the clinical relevance of severe CTE pathology, although the observational study cannot establish that CTE directly caused dementia.

The authors also cautioned that brain donation was non-random, that prevalence at death cannot be equated with CTE prevalence among living players, and that the findings may not generalize to the broader American football population. Further research is needed to clarify the CTE-dementia relationship and to inform future prevention and policy recommendations.