CTE Common Among Young Athletes in Largest Brain Donor Study

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood–brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, told Medscape Medical News.

The findings were published online today in JAMA Neurology.

A Rare Look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke.  

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, McKee said. In this study, females comprised only about 7% of the entire cohort and tended to be younger and play fewer years of a sport than their male counterparts. All of that could lower their risk for CTE, McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”

Early Stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood–brain barrier which could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”

A Message for Clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, McKee said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, MacParkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, US Department of Defense and the US Department of Veterans Affairs. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and MacParkman Foundation during the conduct of the study.

JAMA Neurol. Published online August 28, 2023. Full text

Kelli Whitlock Burton is a reporter for Medscape Medical News covering neurology and psychiatry.

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