Researchers from Boston University, the Cleveland Clinic, Banner Alzheimer’s Institute, and Brigham and Women’s Hospital in Boston have been awarded a $16 million grant from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) to develop methods for diagnosing chronic traumatic encephalopathy (CTE) during life. CTE, a neurodegenerative disease often found in professional football players, boxers, and other athletes who have a history of brain trauma, can currently be diagnosed only by autopsy.
“Diagnosis during life—that’s it,” says lead principal investigator Robert Stern, professor of neurology, neurosurgery, and anatomy and neurobiology at BU School of Medicine (MED), where he is a clinical core director of the NIH-funded Alzheimer’s Disease and CTE Center. “We will be able to truly study issues of incidence and prevalence, examine risk factors, and develop methods to treat and prevent the disease.”
The hallmarks of CTE are changes in behavior, mood, and cognition, including the development of dementia. Doctors diagnose it, postmortem, by examining an abnormal form of tau protein in the brain, and have confirmed cases in people as young as 17 and in athletes who played sports only through high school or college. CTE has also been found in non-athletes—including military service members—who experienced repetitive head impacts.
The new grant will fund a seven-year, multi-center longitudinal study of 240 people: 120 former NFL players (with and without CTE symptoms), 60 former college football players (with and without CTE symptoms), and 60 control subjects who never played contact sports or experienced any type of brain trauma. Researchers will examine the participants at MED and three other centers: Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas; Mayo Clinic in Scottsdale, Arizona; and New York University Langone Medical Center in New York City. In addition to extensive clinical examinations, participants will undergo PET imaging, MRI scans, blood work, and other tests with the potential to detect changes in the brain associated with CTE. Data will be shared with researchers worldwide.
Stern describes the project as “the biggest study of CTE in living subjects to date, in terms of the scope of the science, the number of participants, the breadth and depth and size of the group of investigators, and the amount of the grant.”
And because CTE shares certain features of Alzheimer’s and other neurodegenerative diseases, says Stern, the study will benefit research beyond the field of CTE. “We expect what we learn from this project will have a tremendous impact on the understanding of those other diseases,” he notes.
All confirmed cases of CTE involve some history of repetitive brain trauma, says Stern, but some people are far more susceptible to developing the disease than others. The study will seek to answer why. Do genetic factors put some people at greater risk? How important are the types of hit, the severity of brain trauma, and age of first exposure?
The project involves some 50 investigators from 17 research institutions around the country. The other principal investigators are: Jeffrey Cummings, MD, director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas and Cleveland, Camille and Larry Ruvo Chair of the Neurological Institute of Cleveland Clinic, and professor of medicine at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University; Eric Reiman, MD, executive director of the Banner Alzheimer’s Institute, Phoenix; and Martha Shenton, director of the Psychiatry Neuroimaging Laboratory and senior scientist, Brigham and Women’s Hospital, and professor of psychiatry and radiology at Harvard Medical School.
“There is an urgent need to clarify the clinical and biological consequences of repetitive head impacts in athletics and to use this information to find the best ways to treat and prevent those consequences,” says Reiman.
The new work will expand upon Stern’s recently completed DETECT (Diagnosing and Evaluating Traumatic Encephalopathy Using Clinical Tests) study. “We’re thrilled to receive this incredible grant that will allow us to do so many critically important things,” he adds. “It’s taking a lot of things we’ve been doing and expanding them tremendously.”