New research adds to the growing body of evidence that collision sports involving repeated blows to the head may result in dementia and other forms of cognitive disorders. Researchers from Johns Hopkins Medicine discovered high levels of a repair protein in the brains of former NFL players in a new study using brain scans.
The new findings suggest that brain injury and repair processes persist for years after players end collision sports careers and lead to long-term cognitive problems such as memory loss. The repair protein, 18 kDa translocator protein (TSPO), is known to be present at high levels in the brain in the immediate aftermath of brain injury as part of the inflammatory response and to facilitate repair.
“The findings show that participating in repeated collision sports like football may have a direct link to long-term inflammation in the brain,”
said Jennifer Coughlin, associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
She explains that ongoing research, such as the present one, provide additional information regarding the dynamics of brain healing and the potential long-term effects on cognitive abilities of repetitive brain injuries, even those of a mild nature that are easily recovered from by athletes.
Elevated TSPO Levels
Coughlin describes TSPO as a protein associated with immune cells known as microglia in the brain. This protein is usually present in low concentrations. When a person suffers from any type of traumatic brain injury (TBI), TSPO levels skyrocket as part of the immunological response.
Previous research has found elevated levels of TSPO up to 17 years after damage, indicating that the brain stays in a heightened state of injury and healing long after the traumatic event. In the new study, researchers examined MRI and PET scans that were completed between April 2018 and February 2023 of 27 former NFL players.
They compared these brain scans to those obtained from 27 non-collision sport athletes (swimmers) who had all competed in National Collegiate Athletic Association Division I, II, or III level competition for at least two years. All of the athletes were males between the ages of 24 and 45. Both groups’ participants completed cognitive examinations, including memory tests.
Monitoring, Not Drugs
Former NFL players did worse on learning and memory tests than swimmers, according to the results. Furthermore, scientists discovered that former NFL players had greater levels of TSPO on average than swimmers, particularly in areas of the brain involved with memory and concentration.
“These findings are relevant to both collision sport athletes and other populations that suffer from single or reoccurring mild TBIs, including those experienced during military training and repeated head banging behaviors in children. Since TSPO is associated with repair, we don’t recommend the use of drugs or other interventions at this time. Instead, we will continue to monitor TSPO levels through more research, in order to test for sign of resolution of the injury with more time away from the game,”
said Coughlin.
Coughlin emphasizes that if TSPO continues high, researchers will investigate the factors associated with a sensitivity to long-term injury after a professional career in American football. Finally, they hope to lead techniques for using immunomodulating therapy (perhaps anti-inflammatory medicines) to heal the brain as necessary.
Research Continues
The researchers said they intend to continue tracking TSPO levels in the study’s cohort of former NFL players over time to determine who’s brain heals and who doesn’t. The goal is to inform the creation of drugs and tailored rest periods following repeated brain traumas.
The new research contributes to an expanding body of evidence suggesting that collision sports, such as boxing, soccer, and football, which involve repeated, even low-level blows to the head, may increase the risk of dementia and other cognitive disorders.
Additional researchers from Johns Hopkins; the Concussion Legacy Foundation; Boston University; and the University of Sydney contributed to the work. Support for the research came from the National Institutes of Health.
Abstract
Importance: Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.
Objective: To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.
Design, Setting, and Participants: This cross-sectional study used carbon 11–labeled N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide positron emission tomography ([11C]DPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023.
Main outcomes and measures: Regional [11C]DPA-713 total distribution volume from [11C]DPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains.
Results: This study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized β coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52; P < .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference [MD], −0.70; 95% CI, −1.14 to −0.25; P = .003) and memory (MD, −0.77; 95% CI, −1.24 to −0.30; P = .002), with no correlation between total gray matter TSPO and these cognitive domains.
Conclusions and relevance: In this cross-sectional study using [11C]DPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal [11C]DPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.
Reference:
- Rubin LH, Du Y, Sweeney SE, et al. Imaging Brain Injury in Former National Football League Players. JAMA Netw Open. 2023; 6(10):e2340580. doi:10.1001/jamanetworkopen.2023.40580