POSTED BY GINA DIGRAVIO-BOSTON
A new discovery brings researchers one step closer to diagnosing chronic traumatic encephalopathy in living patients, rather than after death.
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 chronic traumatic encephalopathy (CTE), a neurodegenerative disease.
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 it has only been possible to formally diagnose CTE after a person dies, it has been difficult to track how it affects mental well-being during life.
Now, as reported in the journal Molecular Neurodegeneration, researchers have found 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 coauthor Jesse Mez, codirector of clinical research at Boston University’s CTE Center.
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 coauthor Michael Alosco, associate professor of neurology and a CTE Center codirector of clinical research. “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 Boston University 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’s also an 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.”
The National Institutes of Health, the National Center for Advancing Translational Sciences, the Department of Veterans Affairs, and the Department of Defense funded the work.
Source: Boston University
Original Study DOI: 10.1186/s13024-023-00697-2
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