New study estimates that nearly 75% of former NFL players had CTE at death

In August, a study published in the British Medical Journal estimated that at least 24.5% — roughly one in four — of former NFL players who died from 2016 to 2021 had chronic traumatic encephalopathy (CTE), a degenerative brain disease linked to repeated hits to the head that involves a buildup of abnormal proteins that damage brain tissue.

On Wednesday, a new study — authored by many of the same researchers — came out with even more "sobering" numbers.

A study in JAMA Network Open estimated that approximately 74.5% of former NFL players who died between 2008 and 2023 had CTE, after adjusting for selection bias in brain donation.

Most of what we know about CTE in NFL players comes from autopsy-based studies on voluntarily donated brains, the study pointed out. Players suspected of having CTE are believed to be more likely to donate their brains than those who don't have it.

So, the JAMA study's objective was to estimate the selection-bias-adjusted prevalence of CTE in deceased NFL players.

This study consisted of 2,362 former NFL players, including 396 who had donated their brains. It ultimately determined that, while selection bias certainly inflates donor-based estimates — 93.5% of players studied who were brain donors with neuropathologic evaluation had CTE — the adjusted rate of CTE occurrence that was estimated remained strikingly high (74.5%).

Even the study's "conservative lower-bound analysis" estimated a 63.7% bias-adjusted population prevalence of CTE at death.

All of the NFL players included in the JAMA study played in at least one regular or postseason game.

The study used data from the Understanding Neurologic Injury and Traumatic Encephalopathy brain bank, plus National Death Index records on former NFL players.

"We first quantified the association of a derived clear cognitive symptoms variable with brain donation status and used this estimate to derive a selection ratio representing the relative probability of brain donation by CTE status," the study reads. "We then used this ratio to estimate the prevalence of CTE neuropathology among all deceased NFL players."

"We first quantified the association of a derived clear cognitive symptoms variable with brain donation status and used this estimate to derive a selection ratio representing the relative probability of brain donation by CTE status," the study reads.

"We then used this ratio to estimate the prevalence of CTE neuropathology among all deceased NFL players."

When estimating the "selection ratio," those conducting the JAMA study assumed that brain bank selection was primarily driven by family members of a former NFL player noticing cognitive symptoms.

From there, they used a National Death Index-derived binary dementia cause of death variable to estimate how much more likely people with a dementia-related cause of death were to become donors.

Although the study employed dementia cause of death as a proxy for CTE — due to CTE neuropathology's "large magnitude of association with dementia and cognitive symptoms" — the study acknowledged that many individuals with dementia or mild cognitive impairment will have cognitive symptoms but will die from a non-dementia-related cause.

To compensate for the anticipated measurement error associated with that proxy variable, those conducting the study used population-level estimates of mild cognitive impairment and dementia in former NFL players older than 50 years that were reported in a 2022 study in order to expand their definition of "clear cognitive symptoms."

Notably, the JAMA study also estimated that the bias-adjusted population prevalence of all-cause dementia history during life among the former NFL players studied was 27.2%.

CTE is a condition that, at the moment, can be diagnosed only after death. Following the publication of the aforementioned BMJ study in August, the NFL issued a statement.

"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 wellbeing," an NFL spokesperson said at the time in a statement obtained by Yahoo Sports, in part. "We encourage former players to utilize these resources to identify and seek treatment when they are concerned about their health."

Although CTE risk in all levels of football appears difficult to substantially mitigate, researchers believe treating symptoms of repetitive brain injury during players' lives, particularly during the years between a player's retirement and death, could limit CTE's long-term impact.

Upgrading that health care could complement the league's safety initiatives, which have included helmet regulations, stricter concussion protocols and the dramatic transformation of the NFL kickoff.