A new study estimates about 3 in 4 former National Football League players who died between 2008 and 2023 had chronic traumatic encephalopathy — an even higher level than identified in another recent study of former players.

The new study, published Wednesday in the journal JAMA Network Open, aimed to provide a clearer view of how many former football players have the progressive neurodegenerative disease.

CTE has been linked to repetitive head impacts that often occur during contact sports such as football, soccer and hockey. CTE has also been detected in the brains of people who were in the military and exposed to traumatic explosions as well as victims of domestic violence. The brain trauma causes an abnormal buildup of the protein tau, and changes in the brain can begin years before symptoms are detected.

CTE can be definitively diagnosed only after death, but it has been associated with symptoms that overlap with dementia such as depression, anxiety, memory loss and lack of impulse control.

Previous studies detected the disease in as many as 99% of former NFL players whose brains had been donated for research. However, a significant limitation of these studies was in their potential bias: They were done in a group of people whose brains had been donated by family members who may have noticed symptoms while the person was still alive.

A study published in August found that at least 1 in 4 former NFL players who died between 2016 and 2021 had CTE. The study compared data from death certificates to determine the number of former professional players who had died against the number of brain donors confirmed to have CTE.

For this new study, Dr. Yorghos Tripodis and other researchers from Boston University’s CTE Center wanted to estimate the prevalence of CTE cases among an even broader group of former professional football players, including those who may not have noticed symptoms or donated their brains for research.

The researchers used data from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank combined with National Death Index records from former NFL players. They included brain donor and nondonor NFL players who died between January 2008 and December 2023.

Of 2,362 players who died during that time, 396 had donated their brains for research. Among those, 362 — 93.5% — had been diagnosed with CTE. Almost 70% of the players studied died at the age 70 years or older.

The researchers then looked at death certificates for the 2,362 people who died during the time period, finding that former players who had cognitive symptoms related to dementia were five times more likely to have their brains donated. Donations were more likely to come from families of players who had more symptoms or who died at a younger age.

The researchers adjusted the rate of disease among those who donated their brains to consider who was most likely to donate and applied that to the broader population of former players.

When asked about this newest study, the NFL referred to a statement sent in response to the August study: “The NFL continuously strives to make the game of football safer, including by implementing strategies to reduce concussions and head impacts.

“The NFL remains committed to ensuring that the NFL community has access to a robust – and expanding – set of resources to enhance their physical and mental well being. We encourage former players to utilize these resources to identify and seek treatment when they are concerned about their health.”Tripodis said there are limitations to the new research — no study can remove all selection bias and researchers cannot expand the number to populations other than former NFL players. Evidence of CTE in the brain doesn’t mean all players have symptoms.

“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,” he said. “The symptoms are high, but doesn’t mean that everybody will have symptoms, doesn’t even mean that everybody with symptoms will have the most severe symptoms at the end of their lives.”

Dr. Rachel Grashow, a senior research scientist at Harvard University who was not involved in the new research, said the one “tricky” part to the study is understanding why someone donates their brain. She said that if researchers didn’t account for other factors for brain donation, the math “may not be accurate.”It’s important to separate CTE from dementia, she said. CTE refers to the presence of the protein tau in specific regions in the brain and is measured in stages I through IV. Researchers have found higher rates of dementia among those with stages III and IV CTE only.

“We want to be careful to say that while there are no diagnostic symptoms linked to all of those found to have CTE at all stages, the ones with relatively the most tau protein aggregation show cognitive symptoms — issues with memory, concentration. Cognitive symptoms are different from mood symptoms — depression and anxiety,” Grashow said in an Dr. Julie Stamm, a clinical assistant professor at the University of Wisconsin-Madison, said she was surprised by the high number of presumed CTE cases found in the study after researchers adjusted for who was most likely to donate their brain.

“We talk a lot about the bias of brain banks and how you don’t tend to donate unless you think something’s wrong, and I think that’s been a critique of some of the papers that have come out,” said Stamm, who was not involved with the new research.

Stamm said the NFL can go “a lot farther” in regard to safety to encourage earlier levels of the game to do more, such as not tackling in practices.

“If the NFL says that, the youth levels, the younger levels, they’ll listen, and that will go a long way in decreasing the overall number of impacts over a lifetime that these individuals sustain, which is what we’ve seen increases the risk for CTE,” Stamm said.

Tripodis said that when researchers have a precise estimate of CTE cases from deceased football players, it will motivate them to invest more into research on the disease.

“We’re having significant progress of identifying diagnostic criteria for living patients, designing the clinical trials that will find a cure for the disease,” he said.