Brain pathologies including chronic traumatic encephalopathy (CTE), a neurodegenerative disease, were identified in young deceased athletes, autopsy data showed.
Among 152 contact sports players under age 30 at the time of death, CTE was diagnosed in 41.4%, reported Ann McKee, MD, of the Veterans Affairs Boston Healthcare System and Boston University, and co-authors.
The mean age at death for players with evidence of autopsy-confirmed CTE was 25, the researchers reported in .
Athletes with CTE had other evidence of brain injury, including the presence of a cavum septum pellucidum, enlargement of the ventricles, and more perivascular macrophages in white matter. One player with CTE was female.
Cognitive and neurobehavioral symptoms were frequent among all brain donors, whether or not they had CTE. Suicide was the most common cause of death (57.2%), followed by unintentional overdose (14.5%).
"There is a common misperception that CTE only affects male, elite, professional, contact-sport athletes," McKee told .
"This study shows that CTE can begin very early -- during the teenage years and young adulthood -- in amateur athletes who played only high school or college football, soccer, rugby, or ice hockey, or were wrestlers," she said. "It also shows that it can affect women."
"We know that in over 97% of reported CTE cases, it is caused by repetitive hits to the head," McKee continued. "There is a pressing need to reduce brain injuries, and reduce how many times and how hard athletes who play contact sports are hit in the head. It is imperative that these changes be made at all levels, including amateur and youth sports."
CTE is diagnosed at autopsy by the presence of hyperphosphorylated tau (p-tau) in a unique pattern. Consensus criteria for a clinical syndrome associated with CTE known as traumatic encephalopathy syndrome (TES) were proposed in 2021. Under the criteria, a person diagnosed with TES must have both substantial exposure to repetitive head impacts (RHIs) and core clinical features that include cognitive impairment, impulsivity, explosivity, and emotional dysregulation.
McKee and colleagues studied data from 152 deceased young athletes who donated their brain to the from February 2008 to September 2022. Inclusion criteria were based on the presence of a history of RHIs, regardless of symptoms. Age at death ranged from 13 to 29.
CTE p-tau pathologic findings were classified into four stages using the for CTE. Clinical evaluations with next of kin were conducted for 143 brain donors using online surveys or postmortem telephone interviews. Informants answered questions about cognitive symptoms, mood disturbances, and neurobehavioral dysregulation.
Of the 63 brain donors diagnosed with CTE, 95.2% were diagnosed with mild CTE (stage I or stage II). Three donors had CTE stage III, including one former National Football League player, one college football player, and one professional rugby player.
Brain donors diagnosed with CTE were older by about 4 years than those without CTE. Most players with CTE were men who played amateur sports including American football, ice hockey, soccer, rugby, and wrestling. The sample included one female athlete diagnosed with CTE, a 28-year-old college soccer player.
CTE was often accompanied by other pathologic abnormalities. Cavum septum pellucidum was present more often in the CTE group. Donors with CTE also had more ventricular dilatation, thalamic notching, and perivascular pigment-laden macrophages in the frontal white matter than those without CTE.
In the overall sample, clinical symptoms included depression (70.0%), apathy (71.3%), difficulty controlling behaviors (56.8%), and problems with decision-making (54.5%). Alcohol abuse was reported in 42.9% and drug abuse in 38.3%. There were no differences in cause of death or clinical symptoms based on CTE status.
The findings confirmed that CTE and other brain pathologies can be found in young athletes, but how these pathologies correlated with clinical symptoms was uncertain, McKee and co-authors pointed out. The study suggests some symptoms were not caused by the early tau pathology of CTE, they added.
The case series had several limitations, the researchers acknowledged. It lacked a comparison group, and incidence or prevalence cannot be implied from the findings. Ascertainment bias is a factor in studies that involve brain donations.
Future studies comparing young brain donors with and without RHI may help isolate clinical and neuropathologic effects of RHIs independent of CTE, McKee and colleagues noted.
Disclosures
This work was supported by the Andlinger Foundation, National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, the Nick and Lynn Buoniconti Foundation, the Alzheimer's Association, the Concussion Legacy Foundation, World Wrestling Entertainment, the National Center for Advancing Translational Medicine, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the U.S. Department of Defense, and the U.S. 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 National Institutes of Health and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study. Co-authors reported relationships with the National Institutes of Health, Department of Defense, Alzheimer's Association, and Concussion Legacy Foundation, Oxeia Biopharmaceuticals, National Football League Head Neck and Spine Committee, National Operating Committee on Standards for Athletic Equipment, Houghton Mifflin Harcourt, National Collegiate Athletic Association, National Hockey League, Mackey-White Health and Safety Committee of the National Football League Players Association, Biogen, Psychological Assessment Resources Inc, King-Devick Technologies, Janssen Research & Development, Johnson & Johnson, Rebiscan, World Wrestling Entertainment, Ivivi Health Sciences, Springer/Demos Publishing, Encompass Health, and the National Institute on Neurological Disorders and Stroke.
Primary Source
JAMA Neurology
McKee AC, et al "Neuropathologic and clinical findings in young contact sport athletes exposed to repetitive head impacts" JAMA Neurol 2023; DOI: 10.1001/jamaneurol.2023.2907.