Boxing, Brain Health and Biomarkers: Longitudinal Study Finds Volumetric MRI Changes Over Time

In one of the largest studies to follow MRI brain volumetrics among professional athletes exposed to repetitive head injury (RHI), active boxers were found to have progressive atrophy in regions that differed from those in their older, retired counterparts. In addition, fighters with significant caudate volume loss had measurable cognitive impairment.

The findings, from Cleveland Clinic’s longitudinal Professional Fighters Brain Health Study, were published in Neurology (2020;94:e232-e240).

“The differences in regional brain volumes may reflect distinct pathologic processes that occur at different stages of head injury,” says lead investigator Charles Bernick, MD, MPH, a staff physician with Cleveland Clinic’s Lou Ruvo Center for Brain Health in Las Vegas. “Identifying biomarkers of changing brain structure or function could contribute to understanding these processes and may one day prove to be a useful tool for research and clinical purposes.”

A quest to quantify cumulative head trauma

In recent years, interest in the neurological effects of repeated head trauma in athletes has abounded, but a clear understanding of underlying pathologic mechanisms has been lacking. The study sought to characterize MRI volumetric changes in people with RHI with the aim of identifying biomarkers potentially applicable to determining prognosis, developing risk-reduction strategies and defining cohorts and outcome measures for clinical trials.

Data were drawn from Cleveland Clinic’s Professional Fighters Brain Health Study, an ongoing longitudinal study of licensed mixed martial arts (MMA) fighters and boxers. Participants undergo annual MRI scanning and cognitive testing, as well as blood testing for neurofilament light (NfL) and tau levels.

Study design and results

The study group consisted of 204 participants from the following cohorts:

• 50 active boxers (median age 29; median of 5 fights)
• 23 retired boxers (median age 45; median of 38 fights)
• 100 MMA fighters (combined active and retired, as retired participants were too few to make a separate group) (median age 29; median of 8 fights)
• 31 controls (median age 31; no history of head trauma)

Each participant had completed at least two annual assessments; follow-up averaged 2.6 years, with the longest time between baseline and the last visit being six years.

Key findings included the following:

• Compared with controls, active boxers had average volumetric declines in areas that suggest injured nerve fibers as a result of acute injury:
• Left thalamus (102.3 mm3/y, P = 0.0004)
• Mid anterior corpus callosum (10.2 mm3/y, P = 0.018)
• Central corpus callosum (16.5 mm3/y, P < 0.0001)
• MMA fighters had a similar, but less pronounced, pattern of decline.
• Compared with controls, retired boxers had average declines in regions more typical of progressive neurodegenerative disease, i.e.:
• Left amygdala (32.1 mm3/y, P = 0.002)
• Right amygdala (30.6 mm3/y, P = 0.008)
• Right hippocampus (33.5 mm3/y, P = 0.01)
• Among active fighters, higher baseline NfL levels were associated with a higher rate of atrophy in the left hippocampus and mid anterior corpus callosum, whereas baseline tau showed no associations with volumetric changes.

Overall, no significant differences were found in cognitive testing between controls and active or retired fighters. However, among active fighters, processing speed (Trail-Making Test parts A and B) was poorer in those who had a more than 1.5% average yearly decline in caudate volumes compared with those who did not.

Clinical-volumetric links may emerge over time

“The significance of the different patterns of volumetric decline found in this study has yet to be determined,” Dr. Bernick points out. “However, the findings are intriguing and deserve further scrutiny.”

He explains that the study’s relatively short follow-up to date may be responsible for the paucity of association between volumetric declines and clinical measures, and that new and stronger links may reveal themselves as this longitudinal database grows and ages.

An accompanying editorial by two vascular neurologists from Harvard Medical School and Massachusetts General Hospital states that the study “represents an important advance in the study of athletes subjected to RHI.” The editorialists note: “[F]uture studies building on these results may identify clinically meaningful predictors of irreversible injury and long-term sequelae…permitting risk reduction before patients reach a point of no return.”