More NFL Players Have CTE Than Previously Thought, Study Suggests

At least one in four former National Football League (NFL) players who died from 2016 to 2021 had chronic traumatic encephalopathy (CTE), a retrospective study suggested.

Among all NFL players who died from 2008 to 2021, the possible prevalence of CTE, a disorder associated with repetitive head impacts, ranged between 18.5% and 98.7%, reported Daniel Daneshvar, MD, PhD, of Massachusetts General Hospital in Boston, and co-authors.

Among those who died from 2016 to 2021 — when brain donation was most frequent — possible CTE prevalence was between 24.5% and 97.7%.

Stage IV CTE pathology, indicating the most severe form of the disease, was associated with symptoms of dementia (risk ratio 1.44, 95% CI 1.16-1.78, P<0.001), the researchers wrote in The BMJ.

“Community brain bank studies have shown that CTE affects less than 1% of the general population,” Daneshvar said in a news release. “To find that somewhere between 24.5% and 97.7% of NFL players from that time period had this progressive brain disease is a wake-up call for the NFL and scientific communities,” he noted.

CTE can be detected only at autopsy. In stage IV CTE, phosphorylated tau pathology is widespread across cortical and subcortical structures.

“Previous brain bank studies have reported a high proportion of CTE among former contact sport athletes, including 110 of the first 111 former NFL players examined at Boston University’s UNITE Brain Bank,” noted Tobias Kurth, MD, ScD, of Charité-University Medical Center Berlin in Germany, and Richard Riley, PhD, of the University of Birmingham in England, in an accompanying editorial.

However, brain donation is not random and may be more likely for players who had neurologic symptoms when they were alive, Kurth and Riley pointed out.

“Daneshvar and colleagues recognize this limitation, and their work advances the evidence base in several important ways,” they wrote. “Rather than reporting only the prevalence of CTE among brain donors, they identified a well defined source population comprising all former NFL players who died between 2008 and 2021 and linked this population with data from brain banks. This allowed the investigators to estimate plausible lower and upper bounds for CTE prevalence at death in all NFL players.”

The analysis included 1,712 former NFL players who died from 2008 to 2021, of whom 338 donated their brains and 315 had a diagnosis of CTE.

Brain donations were from American football players who had played at least one NFL game after 1949, the first year hard-shell plastic helmets were mandatory. Most donations (333 brains) were to the UNITE brain banks at the Boston University CTE Center; one was to Mount Sinai in New York City, and four were to the University of California San Francisco Alzheimer’s Disease Research Center brain bank.

Personal information and causes of death according to the National Death Index were obtained for all NFL players who died during the study period. Neuropathologists who were masked to clinical and repetitive head impact histories assessed postmortem CTE diagnosis and stage IV CTE. Clinicians who were masked to neuropathology status reviewed brain donors’ medical records and clinical histories from family members and others to determine a dementia diagnosis.

To account for selection pressure of brain donation status, inverse probability weighting was used to estimate the association between stage IV CTE and study clinician-diagnosed dementia.

Among brain donors, 30.8% had stage IV CTE; 59.8% had dementia according to a study clinician, and 18.6% had neurodegenerative disease listed as primary cause of death. Those with dementia had onset at age 63 and died at age 73.

“Only 40.6% of donors (n=82) with study clinician-diagnosed dementia had neurodegenerative disease listed as the primary or secondary cause of death,” Daneshvar and co-authors observed.

The researchers acknowledged several limitations to their analysis. Not all former NFL players who died during the study window were included; at least 11 other cases of CTE in NFL players who died were reported in the literature or by family members but were not incorporated into the study to maintain consistent methodology. In addition, some family members or other informants may have inaccurately recalled symptoms.

“These data provide insight into the extent to which the higher proportions of death due to neurodegenerative disease are associated with CTE pathology and provide targets for future research studies and policy recommendations,” Daneshvar and colleagues wrote.

More work is needed to clarify the possible effects of high lifetime exposure to repetitive head impacts, especially in other populations, they added.