The University of Glasgow has been jointly awarded $9.7m alongside the University of Pennsylvania to lead an international team of experts in the study of Chronic Traumatic Encephalopathy and neurodegenerative disease.

Dr Willie Stewart, consultant neuropathologist and honorary clinical associate Professor at the University of Glasgow, will be the co-principal investigator on the five year project, which will establish CONNECT-TBI – a program spanning 12 institutions which will study traumatic brain injury (TBI) and related neurodegenerative diseases.

The five-year funding is awarded by the US National Institute of Neurological Disorders and Stroke (NINDS) and National Institute for Aging (NIA), and will help establish diagnostic criteria for Chronic Traumatic Encephalopathy and other forms of traumatic brain injury-related neurodegeneration, termed “TReND”.

Dr Willie Stewart is also the lead author of the FIELD Study which this week published data in the New England Journal of Medicine showing that former professional footballers had an approximately three and a half times higher rate of death due to neurodegenerative disease than expected.

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.

Dr Willie Stewart said: “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.

“Understanding CTE and other forms of traumatic brain injury is crucial in the next steps of understanding the links between contact sports such as football, and neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease and Motor Neurone Disease.”

Co- principal investigator Douglas Smith, MD, director of the Penn Center for Brain Injury and Repair, said: “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.

“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, what these pathologies mean, and what their functions are.

“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.”

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.

Penn investigators also include David F. Meaney, Edward B. Lee, John Q. Trojanowski, Victoria E. Johnson, Douglas J. Wiebe, and Ramon R. Diaz-Arrastia. 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.

First published: 23 October 2019

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