PHILADELPHIA—An international team of experts led by researchers in the Perelman School of Medicine at the University of Pennsylvania and University of Glasgow, has been awarded a $9.7 million, five-year grant from the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute for Aging (NIA) to establish CONNECT-TBI—a program spanning 12 institutions which will study traumatic brain injury (TBI) and related neurodegenerative diseases.
In the past decade, there has been increased concern and awareness regarding the late effects of TBI, specifically, the association between repetitive head impacts in contact sports and the risk of chronic traumatic encephalopathy (CTE) and related dementia. However, other forms of progressive neuropathologies have been observed after TBI, prompting the CONNECT-TBI team to coin an umbrella term, TBI-related neurodegeneration, or “TReND,” of which CTE is one subtype.
The progressive changes in TReND are found in the brains of people who have suffered repeated concussions and in some individuals with a history of a single severe traumatic brain injury. Symptoms of TReND are comparable to other neurodegenerative conditions such as Alzheimer’s disease (AD) and include memory loss, confusion, and depression. However, much about TReND remains unknown. While an estimated 5 to 10 percent of AD and AD-related dementias (ADRD) are thought to result from these types of brain injuries, the field’s understanding of the mechanisms and processes of TReND is still in its infancy.
To improve knowledge of TReND, CONNECT-TBI will form as a “center without walls”—a network of brain banks linked to comprehensive datasets of TBI and AD/ADRD cases. Penn serves as the home institution for the program, which combines expertise and archives from 12 institutions and 26 investigators.
“There’s massive confusion around the term ‘CTE’ and little awareness of other forms of TReND. Much of the general public is under the impression that one concussion will automatically lead to cognitive decline, but none of this has been shown yet,” said principal investigator Douglas H. Smith, MD, director of the Center for Brain Injury and Repair and a professor of Neurosurgery at Penn. “Right now, we’re only at the starting line with research on CTE and other forms of TReND. It’s time now to develop methods, with consensus and panels of experts, to identify all subtypes of TReND and their relative pathological progression.”
The team will analyze the clinical data from the TBI and AD/ADRD cases, including diagnoses of amnestic mild cognitive impairment and various forms of dementia. Furthermore, the program will establish tissue donation protocols for ongoing sample enrollment.
“With the confusion surrounding traumatic brain injury-associated neurodegeneration, we are taking a methodical approach to defining forms of TReND, including CTE. We want to get to the bottom of these pathologies and their implications for any neurocognitive changes,” Smith said.
Co-PI, William Stewart at the University of Glasgow and an adjunct associate professor of Neurosurgery at Penn, agrees, “We expect CONNECT-TBI to deliver an unparalleled research resource which will provide new insights for individuals who have suffered TBI, but have not previously had any information about their risk of developing TReND.”
Penn investigators also include Edward B. Lee, John Q. Trojanowski, Victoria E. Johnson, Douglas J. Wiebe, and Ramon R. Diaz-Arrastia and David F. Meaney. They are joined by experts at University of California San Francisco, Harvard University, Stanford University, Mount Sinai and New York University, Columbia University, University of Toronto, University of Washington, University of Pittsburgh, Uniformed Services University of Health Sciences, and the Department of Defense Medical Research and Materiel Command.
This study is supported by NINDS (U54NS115322-01).
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.