Narrative review: Plasma and MRI biomarkers capture neuronal damage in former professional boxers

Why this study matters

Boxing involves repeated blows to the head. The authors describe it as a risk factor for neurodegenerative disease, in which nerve cells are gradually lost. One such disease is chronic traumatic encephalopathy (CTE), which can be diagnosed only by examining the brain after death. Researchers are looking for biomarkers, measurable signs in blood or on brain scans, that could show damage during life. The authors state that few studies have measured several biomarkers together in people exposed to repetitive head impacts.

What the researchers did

At the memory clinic of Amsterdam UMC in the Netherlands, nine male former boxers aged 46 to 70 were assessed 6 to 30 years after their last professional bout. Eight had boxed professionally, and one had competed only as an amateur. They were compared with male patients who had no history of head injury: 15 with Alzheimer’s disease and 14 with subjective cognitive decline (SCD). The SCD patients had no cognitive impairment on testing and served as healthy controls.

Blood plasma, the liquid part of blood, was tested for six measures. They included GFAP, which the authors describe as a marker of activated astrocytes (support cells in the brain), and neurofilament light (NfL), a marker of damage to nerve fibres. The others were two forms of the tau protein, p-tau181 and p-tau217, and two measures of amyloid beta. MRI scans measured the volume of three sets of brain regions linked in earlier research to Alzheimer’s disease, frontotemporal dementia and CTE. Memory and executive function (skills such as planning) were tested. Five boxers were measured again after an average of 6.8 years.

What they found

Compared with the SCD patients, the boxers had higher blood levels of GFAP, p-tau181 and p-tau217. NfL also tended to be higher, but the difference was not statistically significant (p = .053). GFAP separated boxers from SCD patients best. Compared with the Alzheimer’s patients, the boxers had lower GFAP, NfL and p-tau217, and their amyloid measures did not differ from the SCD patients.

On MRI, the boxers had smaller volumes than the SCD patients in all three sets of regions. The smaller areas included the thalamus and the orbitofrontal cortex on both sides of the brain. Memory and executive function scores did not differ significantly between these two groups. Brain volumes did not differ significantly between the boxers and the Alzheimer’s patients.

At the first visit, four of the nine boxers had mild cognitive impairment on testing. Five were classified as having no traumatic encephalopathy syndrome (TES) under 2021 consensus criteria. The authors describe memory and executive function as the core cognitive criteria of TES. Among the five boxers measured again, NfL and p-tau181 rose over time, all but one scored lower on memory tests, and three progressed in their TES classification. The authors treat these follow-up results as exploratory.

Strengths and limits

Professional career details came from a public record of boxing statistics. Blood markers, MRI and cognitive tests were measured in the same people, and the analyses were repeated with adjustment for age, body mass index and education.

The authors list several limits. Only nine boxers took part, all of them men, which reduces statistical power and means the results cannot be generalized to women. The boxers had less education on average than the SCD patients, and the Alzheimer’s patients were on average seven years older than the boxers. Different MRI scanners were used. The study had no brain tissue data, so the authors cannot tell whether CTE or Alzheimer’s disease lies behind the findings.

The authors also repeated the comparisons with bootstrapping, a method that resamples the data many times. The GFAP difference held (p < .001). The differences in p-tau181, p-tau217 and brain volumes were no longer statistically significant. Among the boxers, blood marker levels were not significantly associated with brain volumes or test scores. MRI volumes were available for 11 patients in each comparison group. The main comparison was made at one point in time, so it shows association and cannot show that boxing caused the differences.

What it adds to research on fighter health

The study measured blood markers, MRI and cognition together in a group of former boxers only. The authors suggest that the boxers showed biological signs of damage to nerve cells without evident clinical decline, and that GFAP, p-tau181 and p-tau217 may be useful markers of risk after repetitive head impacts. They state that the cause of the changes remains unclear. They call for larger studies that include female boxers, follow participants over time and compare findings in life with brain tissue examined after death.