An estimated 75% of professional football players who died over a 15-year span had signs of chronic traumatic encephalopathy, or CTE, a study published Wednesday found.

It’s the highest estimation to date. Most recently, a study published in August by the same group estimated that one-quarter of NFL players who died in a five-year span had CTE. The new study, published in JAMA Network Open, put the figure at three times higher.

Not all people with signs of CTE in the brain go on to experience cognitive decline or dementia, and some people may never experience symptoms at all. A smaller proportion of the former players in the analysis were estimated to have dementia, about 27%, the study found.

The results were surprising, said study leader Yorghos Tripodis, the director of statistics and data management at the Boston University Alzheimer’s Disease and CTE Center. Boston University houses the UNITE Brain Bank, which studies the effects of repetitive head trauma in donated brains, including the brains of athletes, military personnel and others.

“I had to double-check the numbers,” Tripodis said. Still, he said, the number is a best guess. “Right now we don’t know how to diagnose CTE when people are alive, so we are trying to estimate.”

In an emailed statement, an NFL spokesperson said, in part, that the league “continuously strives to make the game of football safer, including by implementing strategies to reduce concussions and head impacts.”

Repeated blows and bias

When a person’s head jolts during an impact, the brain — which is suspended in fluid inside the skull — can slam into the skull or twist, said Dr. Julian Bailes, chair of the neurosurgery department at Endeavor Health in the Chicago area. Each blow is an opportunity for proteins called tau to build up in the brain.

“If that happens over and over again, that damage accrues,” said Bailes, who wasn’t involved with the new research.

The disease can affect parts of the brain involved with regulating behavior and emotions, which can lead to memory loss, depression, violent mood swings and other symptoms. Those symptoms can also be linked to other illnesses.

Although CTE can cause symptoms similar to those of other neurodegenerative diseases, such as dementia and Parkinson’s disease, the signature it leaves on the brain is unique, Bailes said.

One huge hurdle in studying the prevalence of CTE is that the microscopic changes don’t show up on brain scans. That means the condition can be diagnosed only during an autopsy.

Past research has been criticized for bias, since people with cognitive decline and their families are much likelier to either donate their brains to brain banks after they die or ask for autopsies — a previous study by Boston University researchers found that 99% of the brains donated to research by former NFL players had signs of CTE.

In the new study, Tripodis and his team tried to remove as much of that bias as possible to determine a more accurate estimate of CTE rates in former NFL players. They combined data from the UNITE Brain Bank with national death records of other former NFL players who died from 2008 to 2023.

In total, the researchers looked at data from 396 donated brains, plus information from 1,966 other deceased former NFL players. They factored in the ages of death along with estimated rates of mild cognitive impairment and dementia in former NFL players older than 50.

About 93% of the donated brains had signs of CTE, which shows up as structural damage in the brain. The research team calculated that the families of players with symptoms of cognitive decline were about five times likelier to donate brains than the families of players without symptoms and then performed a statistical analysis to correct for that bias.

From there, they estimated that among the roughly 2,360 former players who died during the 15-year time frame, about 1,760, or nearly 75%, had CTE. In comparison, only about 1% of brains donated to banks in the U.S., Austria and Brazil have signs of the disease, the researchers said.

But plenty of people with signs of CTE never develop symptoms, Tripodis said.

The researchers estimated that 27% of the 2,360 players studied had dementia.

The dementia “can be from all causes,” Tripodis said. “But it is very likely that in this specific population that CTE is causing dementia.”

Reducing impacts

Until doctors figure out a way to diagnose CTE while people are still alive, any studies quantifying how many people have the condition will be estimations, said Dr. Jim Kelly, a professor emeritus of neurology at the University of Colorado Anschutz.

“These are all estimates. They had no autopsies on five times as many players who died as they did have autopsies for,” said Kelly, who wasn’t involved in the research.

Some of the autopsies may also have revealed just one or a couple of lesions associated with CTE, “and it seems unlikely that that would lead to anything in terms of a behavior change or dementia,” he said.

Those are difficult studies to do, Bailes agreed. They seek to determine “how many people out there have a condition when not all of them are symptomatic,” he said, adding that the findings are a call for more research into diagnosing CTE in people who are still living.

“If you can’t tell if someone has a certain disease until they’re dead, you really can’t help them,” he said.

In the meantime, prevention is key, Tripodis said: “If you reduce the number of brain injuries, brain impacts, you substantially decrease the risk.”

The NFL has already implemented measures to try to reduce the number of high-impact hits players face. They include redesigned helmets — such as the Guardian Cap — and the dynamic kickoff rule, which leads to lower collision speeds.