The risk of brain damage from a career in the National Football League (NFL) is well known, but a study published yesterday made headlines with an estimate of just how serious that risk may be. Based on an analysis of donated brains, researchers concluded at least one in four NFL players who died between 2016 and ’21 had developed chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with repeated impacts to the head that can cause a host of emotional, physical, and cognitive symptoms.
Although the study, published in The BMJ, provides an indication of the scope of the problem, the condition’s true prevalence among former players remains unknown. Here’s what researchers understand about CTE’s physical effects on the brain—and why it’s been so hard to diagnose in living people.
What’s new about the findings in this study?
A 2017 study of the brains of deceased college and professional football players showed nearly all had died with CTE. (By comparison, in brain bank studies not limited to football players, the condition has been seen in up to 6% of autopsy brains.) But athletes who develop severe cognitive or psychiatric symptoms could be more likely to end up having their brains autopsied, which led to charges of selection bias. “People pooh-poohed [the finding] as exaggerating or alarmist,” says Boston University neuropathologist Ann McKee, a co-author on that paper.
For the new study, McKee and her colleagues, part of a group led by Daniel Daneshvar of Harvard University, looked at data from 878 former NFL players who died between 2016 and ’21, 235 of whom donated their brains for study. By including the broader group of players who died, not just those who had autopsies, the team could avoid selection bias, McKee says. As in the previous study, the lion’s share of brain autopsies showed signs of CTE. That allowed researchers to determine at least one-quarter of the players had the disease when they died. (The team did not report health outcomes from the nonbrain donors in this study.) The true CTE prevalence among former players was likely much higher, they say.
How does CTE harm the brain?
CTE occurs when an abnormal form of the protein tau, similar to that seen in Alzheimer’s and other neurodegenerative diseases, is released from neurons at the site of a head injury and clusters around nearby blood vessels. Over the years, the tau protein spreads beyond the area of impact, eventually reaching brain regions that affect cognition and emotional processing. Patients in the later stages of CTE often have dementia. An autopsy can detect CTE’s signature pathology—accumulations of lesions concentrated in the deep grooves of the cortex—and is for now the only reliable means of diagnosis.
Why can’t CTE be diagnosed while people are alive, like with Alzheimer’s?
The accumulation and distribution of tau protein in Alzheimer’s can be accurately mapped with advanced brain imaging techniques. But imaging does not work as well in CTE, perhaps because tau takes on a different molecular structure. Current blood tests cannot distinguish CTE from Alzheimer’s. Last year, researchers at Washington University in St. Louis published a small study suggesting one experimental blood test, called eMTBR-tau243, could pick up tau in people with CTE—but more research is needed to show how this test could be used clinically.
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Many of the symptoms linked to CTE, such as personality changes, are associated with a broad range of psychiatric and neurodegenerative disorders, making CTE hard to discern, especially in older patients. Complicating matters further, CTE can also co-occur with other brain diseases, including Alzheimer’s and Parkinson’s.
In recent years, scientists have attempted to create clinical criteria for diagnosing CTE. But a study this year found the criteria perform poorly when compared with autopsy diagnosis, prompting fears of false positives and psychological harm to athletes and former athletes. Newer data should help improve the criteria, experts predict.
Can CTE be prevented or treated?
Efforts are ongoing to make football helmets safer, but brain researchers say preventing CTE requires not sustaining repetitive head impacts in the first place.
Suspected CTE symptoms are currently treated off-label with some of the same drugs used in dementia and psychiatric disorders, says neurologist Gil Rabinovici of the University of California San Francisco. But the hope is for disease-modifying drugs that can ward off progression.
Rabinovici helps lead an ongoing study in hundreds of living former professional and college players that aims to identify key features of CTE using a variety of techniques, including MRI and PET scans and neurological exams. He says a consortium of CTE researchers that includes both him and McKee is coming close to publishing the first biomarker in living people, though neither will say what it is.
If a new biomarker is validated, he says, “it will be a game changer,” not only for diagnosis, but also for treatment. It might, for example, allow researchers to test whether an experimental antitau therapy, such as the antisense oligonucleotide that recently showed promise in people with Alzheimer’s, will also work for people with CTE. That, Rabinovici says, is “the million-dollar question.”