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Active professional fighters showed different patterns of brain volume loss than fighters who have retired from the ring, researchers found, and these differences may lead to biomarkers to track changes in people with repetitive head impacts (RHI).

Current boxers and mixed martial artists showed yearly rates of decline in the left thalamus, mid anterior corpus callosum, and central corpus callosum compared with controls (non-fighters), reported Charles Bernick, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and colleagues.

Retired fighters had the most significant volumetric declines in the right hippocampus and in the left and right amygdala compared with controls, which could be the result of a progressive neurodegenerative process like chronic traumatic encephalopathy (CTE) or Alzheimer's disease, they wrote in .

There are no known biomarkers to track changes in brain structure or function over time for people exposed to RHI, Bernick noted.

"Our study suggests that measuring the volumes of certain brain regions using MRI imaging may be such a biomarker, though the findings need validation in other cohorts," he told MedPage Today.

"MRI volumetric measures have been used in the clinic and in clinical trials for a number of years in Alzheimer's disease as an adjunct for diagnosis and following disease progression," Bernick added. "If our findings can be validated in other cohorts such as military servicemen or other contact sports, perhaps MRI volumetrics could be used in a similar way among those exposed to repetitive head impacts."

The findings come from the , a cohort of active professional boxers and mixed martial art (MMA) fighters, retired professional fighters, and controls. from this cohort showed that current boxers and MMA fighters had higher levels of plasma neurofilament light (NfL) and tau than retired fighters or non-fighters.

To participate in the study, active fighters were required to have at least one professional fight within 2 years of enrollment and be training with the intent to compete. Retired fighters were limited to boxers who had a minimum of 10 professional bouts with no sanctioned fights for at least 2 years and who did not intend to return to fighting (there were too few retired MMA fighters to form a separate group, the researchers noted).

Enrollment began in 2011 and is ongoing. Each participant was seen annually; active fighters were seen not sooner than 45 days from a sanctioned fight.

A total of 204 participants who had at least two assessments were evaluated, including:

• 50 current boxers who were about age 29 and had a median of five fights
• 23 retired boxers who were about age 45, with a median of 38 fights
• 100 MMA fighters who were about age 29, with a median of 7.5 fights
• 31 controls who were about age 31, with no history of head injury or military service and did not participate in sports involving head trauma like football or soccer in high school or beyond

In the left thalamus, current boxers lost an average annual volume of 144.8 mm³ (P=0.001 vs controls), compared with a loss of 100 mm³ among MMA fighters (P=0.036 vs controls) and a gain of 42.5 mm³ among controls. In the right hippocampus, retired boxers lost an average of 43.2 mm³ per year, compared with a gain of 9.7 mm³ for controls (P=0.010).

Higher baseline NfL levels were tied to greater volume decline in the left hippocampus and mid anterior corpus callosum.

Cognitive tests showed no significant differences between controls and active or retired fighters at the group level. The subgroup of current fighters with yearly caudate loss, however, showed significant yearly worsening on two processing speed tests (Trails A: P=0.004; Trails B: P=0.015), but no difference on symbol digit or reaction time tests.

"The difference in patterns of longitudinal atrophy between active and retired fighters in this study is intriguing, suggesting that longitudinal MRIs may distinguish between injury responses triggered by recent and remote RHI exposures," observed Christopher Anderson, MD, MMSc, and Jonathan Rosand, MD, MSc, both of the Broad Institute in Cambridge, Massachusetts, in an .

The lack of association between MRI changes and cognitive performance could suggest the brain atrophy seen in this study was not clinically meaningful, or maybe because the test battery was limited and follow-up was only 2.6 years, they noted.

"Future studies linking longitudinal declines in regional brain volumes with significant cognitive performance changes would build a case for the utility of longitudinal MRI as a clinically relevant prognostic tool in RHI populations," they wrote.

The study was voluntary and may be biased toward fighters with concerns about cognitive performance, Anderson and Rosand added. And measuring regional brain volumes over time has inherent retest variability: while the researchers performed several quality control procedures, some random variation may have occurred.

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