Nearly 3 in 4 Former NFL Players Likely Had CTE at Death

Nearly 3 in 4 former National Football League (NFL) players who died between 2008 and 2023 likely had chronic traumatic encephalopathy (CTE), a new study suggested.The population-based cross-sectional analysis included more than 2300 former NFL athletes who played an average of 5 years and died during the 16-year study period, nearly 400 of whom were brain donors.Among donated brains with a determined CTE status, 93.5% showed evidence of the CTE neuropathology. That isn’t necessarily surprising, researchers said, since players with symptoms of CTE during life were about five times more likely to be brain donors.To estimate overall CTE rates for all deceased players, researchers used brain bank data, national death records, dementia and mild cognitive impairment (MCI) data from the 2022 NFL-Long study, and player characteristics, such as years and positions played. That analysis yielded a CTE rate of 74.5%.Researchers also found that more than one quarter of all players had dementia during life, although they noted that the condition may not have been linked to CTE.“The key takeaway is that CTE neuropathology is common, not rare, among former NFL players,” study investigator Yorghos Tripodis, PhD, research associate professor of biostatistics at Boston University School of Public Health in Boston, told Medscape Medical News. “Even after correcting for brain donation bias, about 3 in 4 deceased former players had CTE.”The study was published online on October 28 in JAMA Network Open.Beyond the Brain BankCTE is a neurodegenerative disease associated with repetitive head impacts that can only be definitively diagnosed after death. Most research on CTE in former professional football players has relied on donated brains.Yorghos Tripodis, PhDThis has raised concerns that estimates may overstate how common the condition is because families may be more likely to donate the brains of players who experienced cognitive or behavioral symptoms.In a previous study published in The BMJ, researchers estimated that 24.5%-97.7% of former NFL players who died between 2016 and 2021 had CTE. The wide range reflected uncertainty about how well brain donors represented the broader population of former players.For the new study, researchers examined how differences between brain donors and other former players might affect CTE prevalence results.They used data from the Understanding Neurologic Injury and Traumatic Encephalopathy Brain Bank and National Death Index records to identify 2362 former NFL players who died between 2008 and 2023. Of these, 396 were brain donors and 1966 were nondonors.To account for potential donation bias, researchers compared donors and nondonors using dementia-related causes of death and estimated rates of MCI. They also considered age at death, race, playing position, years in the NFL, Pro Bowl appearances, and Pro Football Hall of Fame status.CTE Remains CommonOf the 387 donors whose CTE status was determined, 362 had CTE neuropathology.After adjusting for differences between brain donors and nondonors, researchers estimated that 74.5% of all former NFL players who died during the study period had CTE neuropathology. Even a conservative sensitivity analysis, designed to yield the lowest plausible estimate, put the CTE prevalence at 63.7%.The findings were broadly consistent across additional analyses using different age limits and methods for estimating MCI. In these analyses, estimated CTE prevalence ranged from 70.3% to 86.1%.The researchers also compared characteristics associated with brain donation. Donors died at a younger mean age than nondonors (67.0 vs 74.7 years) and had played in the NFL for more years on average (7.1 vs 4.7 years). They were also more likely to have a dementia-related cause of death (19.3% vs 11.2%).In the adjusted model, younger age at death, more years played, and White race were associated with a greater likelihood of brain donation.Researchers estimated that 27.2% of deceased former NFL players had a history of all-cause dementia during life, although researchers said that estimate is likely low. They also noted that the study couldn’t determine if the dementia was caused by CTE.The study had several limitations, including reliance on dementia-related causes of death and population-level estimates of MCI to assess cognitive symptoms among nondonors, rather than direct clinical assessments.The findings apply only to deceased former players because CTE cannot yet be definitely diagnosed in living patients, Tripodis said.“We still need a reliable biomarker that accurately differentiates CTE from other neurodegenerative disorders. That would let us follow people over time and learn why some people with CTE pathology develop symptoms while others do not,” he said.In the meantime, cognitive or mood changes in former players should be evaluated clinically, with consideration given to potentially treatable causes such as depression, sleep disorders, and substance use, Tripodis advised, rather than automatically attributing symptoms to CTE.Implications Beyond the NFLIn a statement to Medscape Medical News, the NFL Players Association (NFLPA) stressed the importance of research on football’s long-term health effects and reiterated its commitment to supporting players during and after their careers.“Studies like this are critical to improving our understanding of football’s long-term impacts,” the organization said. “The NFLPA remains committed to supporting scientific research, investing in resources that aid players’ physical and mental well-being, and expanding access to care so that they can experience improved health outcomes during and after their playing careers.”Chris Nowinski, PhDBeyond its implications for former NFL players, the study may also inform efforts to better understand CTE prevalence in other athletes, said Chris Nowinski, PhD, co-founder and CEO of the Concussion & CTE Foundation, who was not involved in the research.“The high rate of CTE seen in the donated brains of former NFL players thus far has been mostly ignored by the football industry because we haven’t been able to quantify selection bias,” Nowinski told Medscape Medical News.He hopes the estimated 75% prevalence will shift the conversation beyond concerns about brain donation bias and spur greater efforts to support former players with suspected CTE and prevent the condition in current players.Additional analyses are needed to estimate CTE prevalence among youth, high school, and college football players, Nowinski said. He added that comparable estimates for athletes in other contact sports are also difficult to establish because brain-bank samples are smaller, limiting researchers’ ability to account for selection bias.“Every brain bank around the world is finding CTE in the majority of professional football, soccer, ice hockey, and rugby players they study,” he said. “But those are all smaller sample sizes, so it’s impossible to calculate selection bias in those communities with the same level of confidence.”Disclosure information for study authors is available in the original study publication. Nowinski reported having no relevant financial disclosures.