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Years of research have shown that athletes who play high-contact sports — like tackle football and soccer — and endure frequent hits to the head risk developing a neurodegenerative disease known as chronic traumatic encephalopathy (CTE). It’s not just the number of years a person plays that can predict the likelihood of developing CTE — it’s also the cumulative force of head trauma.
But a big remaining question is how, and if, CTE is connected to a range of cognitive, behavioral, and neurological symptoms. Since CTE can only be formally diagnosed after a person dies, it’s difficult to track how it impacts mental well-being during life.
Now, a new study from Boston University’s CTE Center edges experts closer to being able to diagnose the disease in the living. In a paper published in Molecular Neurodegeneration, researchers show a clear relationship between the amount of CTE pathology — meaning the accumulation of a protein called p-tau in specific regions of the brain — and the severity of a person’s cognitive and behavioral symptoms during their life. CTE is characterized by an accumulation of misfolded tau protein (p-tau is short for hyperphosphorylated tau) that is different from aging-related changes or any other neurodegenerative disease.
“For the first time, we were able to show a clear dose-response relationship between the amount of CTE pathology and the severity of cognitive and functional symptoms, including problems with memory and executive function,” says Jesse Mez, a CTE Center codirector of clinical research and coauthor on the study.
The research team measured the amount of p-tau pathology across 11 different brain regions in 364 brains with autopsy-confirmed CTE that were donated to BU’s UNITE Brain Bank. They also asked family and friends of the brain donors to complete several standardized assessments to shine a light on their loved one’s cognitive, functional, mood, and behavioral symptoms. The researchers then examined the relationship between the p-tau pathology and results of the behavior assessments.
They found that p-tau pathology across the brain, most predominantly in the frontal lobe, was associated with more reported cognitive functional symptoms, including difficulties in attention, memory, perception, and psychomotor abilities. P-tau in the frontal lobe was associated with some neurobehavioral symptoms, like the reduced ability to control impulses and self-monitor behavior, but overall there was a higher correlation between cognition than neurobehavior.
“A limitation of this study is the use of informants to describe the different symptoms their loved ones experienced,” says study coauthor Michael Alosco, a CTE Center codirector of clinical research and BU Chobanian & Avedisian School of Medicine associate professor of neurology. “This can offer valuable information, but we need to move toward a model where we objectively assess individuals during life and follow them until brain donation.”
Although the National Institute of Neurological Disorders and Stroke has published criteria for diagnosing CTE before death — flagging symptoms related to memory and executive function — they are only approved for use in research, not patients. But the BU team hopes their latest findings validate the symptom criteria, with the hope that they can eventually help living CTE patients obtain a diagnosis and treatment plan.
“These findings provide a clear step forward toward diagnosing CTE in life,” says Mez, who is also a BU Chobanian & Avedisian School of Medicine associate professor of neurology. “Diagnosis is crucial before we can test therapies. With validated in-life diagnostic criteria, we will be able to design clinical trials for therapies.”
Funding for this study came from the National Institutes of Health, National Center for Advancing Translational Sciences, Department of Veterans Affairs, and Department of Defense.