About 3 in 4 former National Football League players who died between 2008 and 2023 may have had chronic traumatic encephalopathy, according to a new study. The estimate is even higher than the level identified in another recent analysis of former players.

The study, published Wednesday in JAMA Network Open, sought to provide a clearer picture of CTE prevalence among former professional football players. Researchers examined a broader population that included players whose families did not donate their brains for research.

CTE is a progressive neurodegenerative disease linked to repetitive head impacts, including those sustained in contact sports such as football, soccer and hockey. It has also been detected in military personnel exposed to traumatic explosions and in victims of domestic violence.

The trauma leads to an abnormal accumulation of the protein tau in the brain. Brain changes can begin years before symptoms are detected, although CTE can be definitively diagnosed only after death.

The disease has been associated with symptoms that overlap with dementia, including depression, anxiety, memory loss and poor impulse control. However, evidence of CTE in the brain does not mean that every affected person experienced symptoms.

Previous research detected CTE in as many as 99% of former NFL players whose brains were donated for study. Those findings carried a major limitation because families who noticed symptoms during a player’s life may have been more likely to donate the brain.

A study published in August estimated that at least 1 in 4 former NFL players who died between 2016 and 2021 had CTE. That research compared death certificate data on deceased former professional players with the number of brain donors confirmed to have the disease.

For the new study, Dr. Yorghos Tripodis and researchers from Boston University’s CTE Center combined data from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank with National Death Index records. They included NFL players who died between January 2008 and December 2023, whether or not their brains were donated.

Among 2,362 players who died during that period, 396 donated their brains for research. Of those donors, 362, or 93.5%, were diagnosed with CTE, while almost 70% of all players studied died at age 70 or older.

The researchers also reviewed death certificates for all 2,362 players. Former players with cognitive symptoms related to dementia were five times more likely to have their brains donated, while donations were also more common among players with more symptoms or those who died younger.

Researchers adjusted the disease rate among brain donors to account for which players were most likely to become donors. They then applied the adjusted rate to the wider population of deceased former players, producing the estimate of about 3 in 4.

The NFL referred questions about the research to a statement issued in response to the August study. The league said it continuously works to make football safer by introducing strategies intended to reduce concussions and head impacts.

The league also said it remains committed to giving the NFL community access to resources supporting physical and mental well being. It encouraged former players who have health concerns to use those resources to identify problems and seek treatment.

Tripodis cautioned that the new research still has limitations because no study can eliminate all selection bias. The estimate also cannot be extended to populations other than former NFL players.

“Our numbers suggest that the prevalence of dementia, which is the most severe type of cognitive symptoms, is four times higher than the general population among the NFL players,” Tripodis said. He added that the high level of symptoms does not mean everyone with CTE will experience symptoms or develop the most severe symptoms.

Dr. Rachel Grashow, a senior research scientist at Harvard University who was not involved in the study, said understanding why families donate brains remains difficult. She also stressed that CTE, which involves tau protein in specific brain regions, must be distinguished from dementia.

CTE is measured in stages I through IV, and researchers have found higher dementia rates only among people with stages III and IV. Grashow said those with relatively more tau accumulation show cognitive problems involving memory and concentration, which differ from mood symptoms such as depression and anxiety.

Dr. Julie Stamm, a clinical assistant professor at the University of Wisconsin-Madison who was not involved in the research, said the adjusted estimate surprised her. She said the NFL could go “a lot farther” on safety by encouraging younger levels of football to reduce impacts, including by eliminating tackling during practices.

Tripodis said a more precise estimate of CTE among deceased football players could encourage greater investment in research. He said researchers are making significant progress toward diagnostic criteria for living patients and clinical trials aimed at finding a cure.

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