Exploring A Potential New Method to Evaluate CTE Progression in Living Patients

As Thanksgiving approaches, millions of people will settle in for a day filled with delicious food and America’s most popular sport, football. Professional football has aired on the holiday since 1953, with Thanksgiving matchups dating back more than a century. Today, the sport is synonymous with the celebration. Unfortunately, the sport has also become synonymous with a more troubling issue: chronic traumatic encephalopathy (CTE).

CTE is an irreversible, progressive neurodegenerative disease linked to repeated head trauma and is currently only diagnoseable postmortem. It is most commonly observed in athletes who participate in contact sports such as American football, boxing, and hockey. The exact prevalence of CTE is unknown, due in part to its postmortem-only diagnosis, overlapping symptoms with other conditions, and the fact that it is not typically listed as a direct cause of death. These factors can make it challenging for clinicians to identify and manage patients who may be affected.

Seeking to shed light on the disease, international researchers and NYU Langone Health developed a test aimed at analyzing the brains of living American football players in hopes of discovering new ways to assess the disease's progression. The study, titled Sulcal morphology in former American football players, evaluated the left superior frontal sulci of male football player’s brains to otherwise healthy male brains.

Led by Shae Datta, MD, co-director of the NYU Concussion Center, the data showed that football players with increasing years of playing experience had wider left occipitotemporal sulci than men not involved in contact sports. Published in Brain Communications, the findings could represent an important step toward identifying markers of CTE risk in living individuals. In an interview with NeurologyLive®, Datta discussed the significance and its potential implications for future approaches to diagnosing CTE during life. She also addressed the ongoing challenges clinicians face in assessing the disease and highlighted several common misconceptions surrounding CTE.

NeurologyLive: Why was it important to research a way to potentially identify CTE prior to death?

Shae Datta, MD: Researching a way to diagnose CTE before death is crucial for providing patients with a definitive diagnosis during their lifetime, allowing for earlier care, treatment, and a better quality of life. It is also important for understanding the disease's progression, identifying risk factors, and developing preventative measures and potential treatments, as well as addressing legal and insurance issues.

What are the biggest takeaways or highlights from this study?

Based on a 2025 study in Brain Communications, former American football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed individuals. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease.

The study also found that earlier age of first exposure to tackle football and longer careers correlated with wider left occipitotemporal sulci. This research helps scientists understand how repetitive head impacts affect the brain structurally, which could pave the way for better diagnostics and treatments for conditions like CTE.

What are some things that may stump neurologists or specialists when it comes to CTE?

As the disease progresses, the accumulation of tau pathology and neurodegeneration leads to cortical atrophy, potentially resulting in sulcal widening and shallowing where such structural alterations may serve as quantifiable markers of disease progression. We do not have a great way to target tau proteins (which are also present in Alzheimer disease).

What are some common misconceptions when it comes to CTE diagnosis, symptoms, or long-term effects?

One misconception is that CTE symptoms are identical to those of Alzheimer or depression. While CTE shares some symptoms with diseases like Alzheimer and depression, such as memory loss and mood changes, it is a distinct condition with overlapping symptoms. It can also present with impulsivity, aggression, and confusion.

Looking ahead at CTE research, what other studies do you think have to be done to advance CTE diagnosis prior to autopsies?Where do you see this kind of research heading in the next 5 years?

The findings in this study could lead to the development of new tools for identifying brain changes associated with repetitive head trauma in living athletes. The link between longer careers and specific brain changes highlights the cumulative impact of playing the sport. As clinicians, we can make decisions to advise athletes to retire when they start showing symptoms or have brain changes on imaging. I hope this type of advanced imaging would be available to patients outside of research capacity.

In the future, these findings could be adopted as early signs, or biomarkers, for CTE, advancing efforts to develop a diagnostic test, so that future therapies can be applied before the damage becomes irreversible.

Transcript edited for clarity.