How Well Can We Detect CTE Risk in Living People?

Repetitive head injuries from sports like football or boxing, military service, and intimate partner violence increase the risk of developing chronic traumatic encephalopathy (CTE), a degenerative brain disease only diagnosable after death. 

In 2019, the National Institute of Neurological Disorders and Stroke assembled a panel of experts to develop criteria that include a history of repetitive head injury and clinical symptoms to help researchers determine who’s at risk of CTE. 

These criteria allowed for the diagnosis of traumatic encephalopathy syndrome (TES), which refers to changes in behavior and mood that might be spotted by a doctor in someone who is still living. Scientists believe that TES is a potential precursor to CTE, which is defined by the abnormal aggregation of tau in the brain in those with previous head injuries. CTE currently requires a postmortem exam of the brain to diagnose. 

Dr. John D. Arena, a neurosurgeon and researcher at the University of Pennsylvania, wanted to test how well TES criteria matched up to CTE in post-mortem evaluations. In his recent study published in Nature Medicine, 75 percent of people who fit the TES criteria did not have CTE.

The clinical features that included cognitive and behavioral changes, “did not improve the performance,” Arena told Being Patient, in predicting CTE beyond repetitive head injury alone. 

But other experts who were involved in developing the latest criteria, who are conducting their own study in a CTE-specific brain bank, point to key limitations in the study.

Does TES predict CTE?

To diagnose CTE, pathologists examine the brain post-mortem, looking for toxic tau proteins. In Alzheimer’s and other neurodegenerative conditions, tau forms toxic tangles. Unfortunately, the tools used to detect tau for Alzheimer’s don’t work for CTE, because of differences in shape and location of the tau. If TES could reliably predict CTE, it would open the door to more observational studies tracking the disease and trials attempting to intervene. 

This was the first published study assessing the validity of this criteria. 

Arena and his colleagues analyzed the brains and medical histories of 1,038 donors to the Penn Brain Bank. Of those, 162 had a history of repetitive head injury or traumatic brain injury. In 32, the injury was linked to sports like boxing, soccer, and football. To fit the criteria for TES, the researchers also checked to see whether the donors had a history of cognitive or behavioural problems, in the absence of other diseases and neurodegenerative conditions that might better explain the symptoms. 

Only 25 met the criteria for TES, and six, or 24 percent, showed signs of CTE in the brain — deposits of toxic tau proteins inside brain cells. Seven other donors in the brain bank had CTE but didn’t fit the clinical criteria for TES. 

In fact, TES criteria performed about as well as using a history of repetitive head injury in predicting who had CTE. For Arena, the results suggested that the cognitive and behavioral problems which are assessed as part of TES criteria did not improve the accuracy of detecting CTE.

Michael Alosco, co-director of Boston University’s CTE Center, who wasn’t involved in the study and one of the experts who contributed to the latest TES guidelines, told Being Patient that researchers didn’t have data tracking how long each individual played contact sports, which Alosco said would be key to fulfilling the criteria. Instead, they estimated the exposure based on the highest level of sports play. 

What’s next for TES and CTE?

Since the researchers used a neurodegenerative disease brain bank rather than one focused on CTE, few of the donors had the disease. “As the prevalence of the disease is low,” said Alosco, “the probability that the disease is present if you test positive also goes down,” deflating the accuracy of TES.

Alosco and other researchers are evaluating TES from CTE-specific brain banks in donors where they have data on repetitive head injury exposures. The preliminary findings assessing 193 donors were presented in 2025, finding that TES criteria was 79 percent accurate at predicting who had CTE and 84 percent accurate at ruling it out. The research has not been published in a peer-reviewed scientific journal.

Researchers are also working on developing blood, cerebrospinal fluid, and PET imaging biomarkers to more accurately detect CTE in living individuals.

“The goal is always to find ways to improve our ability to predict who has CTE,” said Alosco. “When you can add in more information, particularly biomarkers, that’s what’s going to get us to that place.”