Although both active and retired professional boxing and mixed martial arts (MMA) fighters experience brain volume loss after repetitive head impacts (RHIs), different brain regions are affected, a new study shows.

The distinction suggests that different pathways are at work in traumatic brain injury, the researchers conclude.

"The different regions that showed decline between active and retired fighters was one of the most important findings," lead author Charles Bernick, MD, MPH, of the Cleveland ClinicLou Ruvo Center for Brain Health in Las Vegas, Nevada, told Medscape Medical News.

"We speculate that the changes we saw in volumes of deep brain structures like the thalamus and corpus callosum in active fighters may represent the delayed effects of repeated axonal injury, whereas in the retired fighters, the volume changes in the hippocampus and amygdala may represent a neurodegenerative process," Bernick added.

The study was published online December 23, 2019, in Neurology.

Monitoring changes in regional brain volumes on MRI can be useful for following structural brain changes over time, prior research suggests.

The current study builds on previous investigations that linked RHIs to volume changes in specific brain regions. Those earlier studies, however, were cross-sectional, the authors note, and "less is known about using volumetric MRI techniques in a longitudinal manner in those exposed to RHI."

To learn more about the long-term effects of RHIs, the investigators assessed participants in the Professional Fighters Brain Health Study (PFBHS). The ongoing PFBHS started in 2011. Annual assessments include high-resolution T1-weighted anatomic MRI of boxers, MMA athletes, and age- and education-matched control persons. Participants also undergo computer-based cognitive testing, and they report RHI exposure history at each evaluation.

The study population of 204 participants included 50 active boxers, 100 active MMA fighters, 23 retired boxers, and 31 control persons. There were not enough retired MMA fighters to create that cohort.

The mean age of the active boxers was 29 years, and the mean number of fights was five. For active MMA athletes, the mean age was 29, and the mean number of fights was eight. For retired boxers, the mean age was 45 years, and the mean number of fights was 38. For the control group, the mean age was 31; none of the control persons had a history of head trauma.

Compared with control persons, active boxers experienced an average annual volume decrease of the left thalamus of 102.3 mm3/yr, a significant difference (P = .0004). They also displayed decreases in the mid anterior corpus callosum of 10.2 mm3/yr (P = .018) and in the central corpus callosum of 16.5 mm3/yr (P < .0001).

The active MMA fighters also experienced decreases over time, although these were less pronounced. The left thalamus decreased by 57.5 mm3/yr (P = .036), and the central corpus callosum decreased by 9.7 mm3/yr (P = .007).

The retired boxers experienced the most significant decreases in volume compared to control persons, but in different areas. For them, the left amygdala decreased by 32.1 mm3/year (P = .002); the right amygdala, by 30.6 mm3/yr (P = .008); and the right hippocampus, by 33.5 mm3/yr (P = .01).

Bernick and colleagues also assessed serum neurofilament light (NfL) levels. Higher NfL levels were found to be associated with significantly greater decreases in volumes of the left hippocampus, at 33.2 mm3/yr (P < .001), and of the mid anterior corpus callosum, at 7.68 mm3/yr (P = .015).

Among fighters with higher NfL levels, there was also a trend toward lower volumes of the left amygdala, the right thalamus, and the mid corpus callosum over time.

In contrast, higher baseline tau levels were not associated with regional volumetric changes.

Bernick and colleagues previously reported that active fighters have higher serum NfL levels in general compared to retired fighters or control persons. "Thus, the current finding that, within the active fighter group, those with higher baseline NfL levels were more likely to show regional volumetric decline suggests that this measure may have predictive properties in identifying individuals who may be at risk of ongoing structural brain injury," the researchers note.

"Whether cessation of exposure to RHI in those who have elevated NfL levels will halt this volume loss over time needs further investigation," they add.

The researchers found no significant differences in trajectory of cognitive test scores between control persons and active or retired fighters at a group level.

Potential limitations of the study include the fact that it included few women, making it difficult to assess for volume changes by sex. In addition, the average follow-up time was 2.6 years, which may limit the findings.

"Volumetric MRI brain imaging may be able to detect accumulating injury or disease progression in individuals who are exposed to extensive repetitive head impacts," Bernick said.

He added a caveat that the findings need to be validated in other populations in which repetitive head trauma occurs, such as military personnel or athletes who participate in other contact sports.

Going forward, the researchers also might explore whether a multimodal approach that combines volume measures with other potential biomarkers could improve detection of changes at an individual level. Furthermore, if the MRI volumetric measures are validated, they could serve as clinical trial outcomes in future studies of RHIs, Bernick said.

The differences in brain atrophy between active and retired fighters "is intriguing, suggesting that longitudinal MRIs may distinguish between injury responses triggered by recent and remote RHI exposures," Christopher D. Anderson, MD, and Jonathan Rosand, MD, write in an accompanying editorial.

"Atrophy over time in these brain regions could reflect the sequelae of ongoing axonal injury," they note. The decreases in amygdala and hippocampus volumes in the retired fighters could reflect a neurodegerative process, such as that described in Alzheimer disease and chronic traumatic encephalopathy.

They describe the study as "an important advance in the study of athletes subjected to RHI who are at risk for early and long-term neurologic complications." Strengths of the research include a relatively large population, inclusion of people with both recent and remote trauma, and a well-characterized control group, they add.

"Further imaging studies will be needed to replicate and extend these findings," conclude Anderson, who is affiliated with the Henry and Allison McCance Center for Brain Health, the Department of Neurology, and the Center for Genomic Medicine at Massachusetts General Hospital in Boston, and Rosand, who is affiliated with the Program in Medical and Population Genetics at the Broad Institute in Cambridge, Massachusetts.

Bernick received research funding from Ultimate Fighting Championship, Top Rank Promotions, Haymon Boxing, Bellator/Spike TV, and the UCLA Dream Fund. Anderson and Rosand have disclosed no relevant financial relationships.

Neurology. Published online December 23, 2019. Abstract, Editorial

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Repetitive Head Impacts: A One-Two Punch for Pro Fighters? - Medscape