A new imaging study of professional boxers and mixed martial arts fighters finds that repeated head trauma appears to push the brain’s glymphatic “cleanup” system into overdrive at first, before its function declines with increasing knockouts. The MRI-detected changes, to be presented at the Radiological Society of North America’s annual meeting, could offer early warning signs of future neurodegenerative risk.
Professional fighters face significant risks from repeated head impacts. According to the Radiological Society of North America (RSNA), sports-related traumatic brain injuries account for up to 30 percent of all traumatic brain injury cases, with boxing and mixed martial arts among the leading contributors.
The new research, drawn from Cleveland Clinic’s Professional Athletes Brain Health Study (PABHS), examined how these impacts might affect the brain’s glymphatic system — a network of fluid-filled channels that helps flush out waste materials such as metabolites and toxins.
The glymphatic system operates through channels surrounding blood vessels and functions somewhat like the body’s lymphatic system. It helps maintain fluid balance, deliver nutrients and immune cells, and protect brain tissue from injury. To evaluate this system, researchers used diffusion tensor imaging along the perivascular space (DTI-ALPS), a specialized MRI technique that measures water movement along pathways linked to glymphatic flow. The DTI-derived ALPS index serves as a non-invasive marker of glymphatic function; lower values have been associated in prior studies with cognitive decline and conditions such as Alzheimer’s and Parkinson’s disease.
"The recently discovered glymphatic system is like the brain’s plumbing and garbage disposal system," said lead author Dhanush Amin, M.D., a researcher with the University of Alabama at Birmingham and Cleveland Clinic Nevada at the time of the study. "It’s vital for helping the brain flush out metabolites and toxins."
In the analysis, the team drew on baseline data from PABHS, which tracks roughly 900 active fighters, about 300 of whom have been monitored for at least three years. For this project, the researchers evaluated 280 athletes. Of these, 95 showed cognitive impairment at the start of the study, while 20 demographically matched healthy individuals served as controls.
Using the DTI-ALPS method, the researchers assessed glymphatic activity and examined how the ALPS index related to each athlete’s history of knockouts. They also compared cognitively impaired fighters with those without measurable impairment.
Their expectations did not fully match the results. The investigators initially hypothesized that repeated head impacts would cause lower ALPS values in cognitively impaired fighters compared with non-impaired fighters, and that ALPS would be closely and negatively correlated with total knockouts in the impaired group. Instead, cognitively impaired fighters showed significantly higher glymphatic index values at baseline, suggesting that the brain’s cleaning system may be working harder in response to trauma. However, in these fighters, ALPS values fell sharply as the number of knockouts increased, indicating a decline in glymphatic function with accumulating head injury.
"We believe that the glymphatic index was initially high in the impaired athlete group because the brain initially responds to repeated head injuries by ramping up its cleaning mechanism, but eventually, it becomes overwhelmed," Dr. Amin said in materials released by RSNA. "After a certain point, the brain just gives up."
The study also found that fighters without cognitive impairment had lower right-sided and overall glymphatic index values than impaired fighters, and the pattern of how glymphatic activity related to knockout history differed significantly between the two groups. According to RSNA’s summary of the findings, glymphatic decline in the presence of ongoing head trauma may occur years before clinical symptoms emerge, raising the possibility of earlier detection of risk.
"If we can spot glymphatic changes in the fighters before they develop symptoms, then we might be able to recommend rest or medical care or help them make career decisions to protect their future brain health," Dr. Amin said.
Co-authors on the study include Gaurav Nitin Rathi, M.S., Charles Bernick, M.D., and Virendra Mishra, Ph.D., according to the RSNA release.