CTE Prevalence at Death in Former NFL Players

Key Takeaways

• Among former National Football League (NFL) players who died during 2008-21 in the post-1949 hard-shell helmet era, chronic traumatic encephalopathy (CTE) prevalence at death was estimated as a bounded range rather than a single definitive figure.
• During 2016-21, when brain donation was most frequent, the possible prevalence of CTE at death ranged from 24.5% to 97.7%.
• Dementia was common among donors, and stage IV CTE was significantly associated with clinician-adjudicated dementia.
• Only 40.6% of donors with clinician-adjudicated dementia had neurodegenerative disease listed as a primary or secondary cause of death.

Chronic traumatic encephalopathy can be definitively identified only after death, which makes disease burden difficult to estimate in people with long exposure to repetitive head impacts. Former NFL players are a clinically important group for this question because the authors sought to assemble a fully enumerated mortality cohort that could be compared with neuropathological findings in donated brains. The clinical uncertainty extends beyond prevalence because the relation between severe pathology, dementia documented before death, and death-certificate coding remains incomplete.

In a BMJ cohort study, investigators conducted a retrospective population-based analysis of US former NFL players from the post-1949 hard-shell helmet era. During 2008-21, 1,712 former NFL players died and 338 donated brains for neuropathological evaluation through the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) and University of California, San Francisco Alzheimer’s Disease Research Center (UCSF ADRC) brain banks. National Death Index (NDI) personal information and causes of death were obtained for all decedents. Neuropathologists were masked to clinical and playing histories, and clinicians were masked to neuropathological status when adjudicating dementia from medical records and informant-based histories. Investigators then estimated minimum and maximum prevalence at death by comparing donor findings with all deaths and used inverse probability weighting in the stage IV CTE-dementia analysis to address selection pressure from brain donation.

Among donors, 315 of 338 had CTE, or 93.2%, yielding a study-defined possible prevalence at death of 18.5% to 98.7% across all former NFL player deaths during 2008-21; the authors note the lower bound is conservative and could be higher because additional reported NFL CTE cases outside the included brain banks were not counted. In the later years when donation became more frequent, the lower bound rose and the prevalence interval narrowed, but the data still supported a bounded estimate rather than a single population value.

Within the donor group, 104 had stage IV CTE and 202 had clinician-adjudicated dementia. Stage IV CTE was associated with clinician-adjudicated dementia, with a risk ratio of 1.44, 95% CI 1.16 to 1.78; P<0.001. The donor-level clinical signal therefore linked the most severe neuropathology with dementia documented from premortem records.

Prevalence was reported as lower and upper bounds because brain donation was incomplete and non-random. Inverse probability weighting addressed differential donation but not differential mortality, and the stage IV CTE-dementia association was observational and restricted to donors. Dementia ascertainment relied partly on retrospective informant histories and record review, whereas CTE remained a postmortem diagnosis. These findings apply to deceased former NFL players with high exposure to repetitive head impacts and should not be generalized beyond that population.

The authors concluded that the later donation years placed the minimum prevalence at death near one quarter of deceased former NFL players. They also reported that dementia among donors tracked with severe CTE pathology, while death records captured only part of the neurodegenerative burden identified through combined clinical and neuropathological assessment.

Clinician Questions

Why did investigators report a range for CTE prevalence at death in former NFL players instead of a single prevalence estimate?

Only a subset of deceased former NFL players underwent neuropathological evaluation, so investigators bounded prevalence rather than claiming a single definitive population estimate. The minimum used donors with CTE divided by all NFL deaths in the period, whereas the maximum used one minus donors without CTE divided by all NFL deaths.

Do CTE-at-death findings in former NFL players apply to living players or to the broader football population?

These findings were limited to deceased former NFL players from the post-1949 hard-shell helmet era, and CTE cannot currently be definitively identified in living people. The authors said the cohort’s high exposure to repetitive head impacts limits generalizability beyond former NFL players and does not establish prevalence in the broader American football community.

What selection issue did inverse probability weighting address in the stage IV CTE and dementia analysis?

Inverse probability weighting was used to address unequal likelihood of brain donation when estimating the association between stage IV CTE and clinician-adjudicated dementia among donors. The weighting incorporated donor-status covariates including age at death, race, position, Hall of Fame status, Pro Bowl games, body mass index at NFL debut, years in the NFL, and cause of death, but the authors said it did not address differential mortality and that donor-only analyses may still be vulnerable to selection or collider bias.

Recommended Reading

• For more on concussion care in athletes: Breakthrough Technology Improves Concussion Assessment and Player Safety