At least 1 in 4 former NFL players who died between 2016 and 2021 may have had chronic traumatic encephalopathy (CTE), according to a new study published Monday in The BMJ.

Researchers from Mass General Brigham, Boston University, and the Concussion & CTE Foundation analyzed 1,712 former NFL players who died between 2008 and 2021 and found that 338 brains were donated for examination.

Among those donors, 315 of them, or 93.2%, had evidence of CTE, a degenerative brain disorder that can be caused by repeated head injuries.

“These repeated impacts are associated with an abnormal buildup of tau protein that damages brain cells and may eventually contribute to problems with memory, thinking, behavior and mood,” Dr. Leah Croll, a neurologist at Maimonides Medical Center and assistant professor of neurology at SUNY Downstate Health Sciences University, who was not involved in the study, told ABC News. “Right now, CTE can only be definitively diagnosed after death.”

Based on those findings, the authors estimated that the minimum prevalence of CTE among all former NFL players who died between 2016 and 2021 was 24.5%.

The study also examined whether more severe disease was linked to cognitive decline. Among brain donors, nearly 60% had dementia and 90.4% of those with the most severe form of CTE (stage IV) had dementia.

After accounting for differences between donors and non-donors, stage IV CTE was associated with a 44% higher risk of dementia.

Researchers noted that many cases of dementia were not captured on death certificates, suggesting the burden of neurodegenerative disease among former players may be underestimated.

“These findings are extremely concerning,” Croll noted. “The true number could be substantially higher, and even this minimum estimate suggests that CTE is not a rare outcome among former NFL players. It’s a sobering realization — neurodegenerative disease is a common occupational hazard for these players.”

According to Dr. Daniel Daneshvar, chair of physical medicine and Rehabilitation at Mass General Brigham, community brain bank studies have shown that CTE affects less than 1% of the general population.

“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,” Daneshvar said in a statement.

The researchers said that future studies should look at athletes who played more recently, and that prevention efforts need to focus on reducing repetitive head impacts that lead to CTE risk, not just concussions. 

In a statement to ESPN, the NFL said it “continuously strives to make the game of football safer, including by implementing strategies to reduce concussions and head impacts.”

The statement went on, “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.”

In a statement to ABC News, the NFL Players Association, the union that represents football players in matters including working conditions, said the study is “a sobering reminder that football carries real risks, and those risks can have lasting consequences for players and their families. It also reinforces one of the NFLPA’s core priorities: improving player safety and supporting players throughout their lives, both during and after their careers.”

The union said the study should serve as “a call to acton” to continue research, treatment development and improving access to care for those affected by long-term effects of the game.

ABC News’ Youri Benadjaoud and Dr. Jade Cobern contributed to this report.