Repeated head impacts may quietly break the brain’s cleanup system

Sports-related traumatic brain injuries represent up to 30 percent of all brain injury cases, with boxing and mixed martial arts among the leading contributors. Sustained head impacts over time are known risk factors for both neurodegenerative and neuropsychiatric conditions.

How the Glymphatic System Removes Waste From the Brain

The glymphatic system consists of fluid-filled channels that help flush waste materials from the brain. Its function is somewhat similar to the lymphatic system that operates throughout the body.

"The recently discovered glymphatic system is like the brain's plumbing and garbage disposal system," said Dhanush Amin, M.D., the study's lead author and a researcher at the University of Alabama at Birmingham and Cleveland Clinic Nevada. "It's vital for helping the brain flush out metabolites and toxins."

To study this system, the researchers used diffusion tensor imaging along the perivascular space (DTI-ALPS), a specialized MRI method that measures how water moves in and around the channels linked to glymphatic flow. These pathways also help maintain fluid balance, deliver nutrients and immune cells, and provide protection against injury.

MRI Biomarkers Reveal Early Signs of Brain Decline

The DTI-derived ALPS index is a non-invasive marker of glymphatic function. Lower ALPS values can indicate cognitive decline and have been associated with the development of conditions such as Alzheimer's and Parkinson's disease.

"When this system doesn't work properly, damaging proteins can accumulate, which have been linked to Alzheimer's and other forms of dementia," said Dr. Amin, now an assistant professor of neuroradiology at the University of Arkansas for Medical Sciences. "Studying this system gives us a new window into understanding and possibly slowing memory loss."

Their analysis drew from baseline data in Cleveland Clinic's Professional Athletes Brain Health Study (PABHS), which tracks roughly 900 active fighters, about 300 of whom have been monitored for at least three years. For this study, the team evaluated information from 280 athletes. Among them, 95 showed cognitive impairment at the start of the study, and 20 healthy individuals served as demographically matched controls.

Higher Initial Glymphatic Activity Followed by Decline

Using the DTI-ALPS technique, the researchers evaluated glymphatic activity among all participants and examined how the DTI-derived ALPS index related to the number of knockouts each athlete had experienced. They also compared impaired fighters with those who showed no cognitive impairment.

"We thought repeated head impacts would cause lower ALPS in cognitively impaired fighters compared to non-impaired fighters," Dr. Amin said. "We also expected the ALPS measurement to be significantly correlated with the total number of knockouts in the impaired fighters."

Their results were unexpected. Impaired athletes showed significantly higher glymphatic index values at first, but those values fell sharply over time as the number of knockouts increased. Glymphatic function continued to drop in fighters who sustained ongoing head trauma.

"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. "After a certain point, the brain just gives up."

The study also noted that athletes without cognitive impairment had lower right-sided and overall glymphatic index values than impaired fighters. The pattern of how glymphatic activity related to knockout history differed significantly between the two groups.

Early Detection Could Protect the Long-Term Brain Health of Fighters

Dr. Amin emphasized that understanding how repeated head impacts affect the glymphatic system is essential for identifying neurodegenerative risk early in athletes who participate in contact sports.

"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," he said.

Co-authors on the study are Gaurav Nitin Rathi, M.S., Charles Bernick, M.D., and Virendra Mishra, Ph.D.