Years of dedicated research have consistently highlighted the elevated risk of chronic traumatic encephalopathy (CTE) among athletes engaged in high-impact sports. These sports, including football and soccer, are characterized by frequent head impacts, leading to concerns about long-term neurological health. It’s not merely the duration of participation in these sports, but crucially, the cumulative force of repeated head trauma that significantly increases the likelihood of developing this debilitating neurodegenerative disease.
However, a critical challenge in CTE research has been understanding the intricate connection between CTE pathology and the array of cognitive, behavioral, and neurological symptoms experienced by individuals during their lifetime. Historically, definitive CTE diagnosis has only been possible through post-mortem examination of brain tissue, limiting the ability to study its impact on mental well-being in living individuals and hindering the development of effective treatments.
Groundbreaking work from the Boston University (BU) CTE Center is now bringing experts significantly closer to achieving Cte Diagnosis In Living individuals. A newly published study in Molecular Neurodegeneration unveils a compelling correlation between the extent of CTE pathology, specifically the accumulation of phosphorylated tau protein (p-tau) in specific brain regions, and the severity of cognitive and behavioral symptoms observed during life. This p-tau accumulation is a hallmark characteristic differentiating CTE from age-related changes and other neurodegenerative conditions.
According to Dr. Jesse Mez, a co-director of clinical research at the BU CTE Center and coauthor of the study, “For the first time, we have established a clear dose-response relationship. This means that as the amount of CTE pathology increases, so does the severity of cognitive and functional symptoms, notably impacting memory and executive function.”
To conduct this research, the team meticulously analyzed 364 brains with autopsy-confirmed CTE, all donated to the BU UNITE Brain Bank. Crucially, they also gathered comprehensive information on the donors’ cognitive, functional, mood, and behavioral symptoms during life through standardized assessments completed by family and friends. By correlating the p-tau pathology levels with these detailed behavioral assessments, the researchers were able to identify significant patterns.
The findings revealed that widespread p-tau pathology across the brain, with a particular concentration in the frontal lobe, was strongly associated with a greater incidence of reported cognitive functional symptoms. These included impairments in attention, memory, perception, and psychomotor skills. Furthermore, p-tau accumulation in the frontal lobe also showed links to certain neurobehavioral symptoms, such as reduced impulse control and difficulties with self-monitoring. Interestingly, the correlation was stronger between p-tau pathology and cognitive symptoms compared to neurobehavioral symptoms.
Dr. Michael Alosco, another co-director of clinical research at the CTE Center and associate professor of neurology at BU Chobanian & Avedisian School of Medicine, acknowledges a limitation of the study. “Relying on informants to retrospectively describe symptoms has inherent limitations,” he states. “While valuable, the next critical step is to develop models for objectively assessing individuals while they are living and longitudinally following them until brain donation to confirm diagnosis.”
While the National Institute of Neurological Disorders and Stroke has proposed research criteria for diagnosing CTE in living individuals based on symptoms affecting memory and executive function, these criteria are not yet approved for clinical diagnosis in patients. The BU research team is optimistic that their latest findings will provide crucial validation for these symptom-based criteria. Their hope is that this validation will pave the way for living CTE patients to receive accurate diagnoses, enabling the development of targeted treatment plans and interventions.
“These findings represent a significant stride forward in our ability to diagnose CTE during life,” emphasizes Dr. Mez. “Accurate diagnosis is paramount for the development and testing of potential therapies. With validated in-life diagnostic criteria, we can finally design robust clinical trials to evaluate the effectiveness of these therapies.”
Funding for this vital research was provided by the National Institutes of Health, National Center for Advancing Translational Sciences, Department of Veterans Affairs, and Department of Defense.
