Edited by: Michael E. Buckland, The University of Sydney, Australia
Reviewed by: Christine M. Baugh, University of Colorado Anschutz Medical Campus, United States; Sarah C. Hellewell, The University of Sydney, Australia
This article was submitted to Neurotrauma, a section of the journal Frontiers in Neurology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Multiple epidemiological studies have demonstrated that male athletes have been shown to be at lower risk for sports-related concussion than female athletes within both practice and competition across numerous sports (
In addition, recent professional fight records comparing fight outcomes across men and women may be an indication of the different rates of repetitive head impact exposure, suggesting a need for further exploration of sex differences. When examining Nevada state fight records from 2015 through 2017, it appears that women are less likely to be knocked out (KO) or sustain a technical knockout (TKO) than male fighters overall [please see
2015 to 2017 Nevada commission fight records.
Boxer | 34 | 170 | 296 | N/A | 500 (41) |
Male boxers | 33 | 168 | 288 | – | 489 (41) |
Female boxers | 1 | 2 | 8 | – | 11 (27) |
Mixed martial artists | 14 | 136 | 263 | 137 | 550 (27) |
Male mixed martial artists | 12 | 123 | 225 | 107 | 467 (29) |
Female mixed martial artists | 2 | 13 | 38 | 30 | 83 (18) |
Martial artists | 4 | 14 | 34 | N/A | 52 (35) |
Male martial artists | 4 | 12 | 32 | – | 48 (33) |
Female mixed martial artists | 0 | 2 | 2 | – | 4 (50) |
The participants were drawn from an ongoing longitudinal observational study of professional combat sport athletes, the Professional Fighters Brain Health Study [PFBHS; (
The study was approved by the local institutional review board (#10-944), and written informed consent was obtained from all study participants. Study visits for all participants included in these analyses were performed at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Nevada between 03/30/2011 and 10/18/2017 [for a detailed explanation of the study methods, see Bernick et al. (
The study cohort consisted of all 55 women fighters enrolled in the PFBHS to date and 55 male fighters who were matched with the female fighters on the following variables: age, years of education, ethnicity, and type of competitive fighting, including boxing, mixed martial arts (MMAs), and martial arts (MAs; e.g., kickboxing, Muay Thai, judo). Both retired and active professional fighters were included in the analyses for this study. The females were matched as closely as possible on the following variables in order of priority: (1) age, (2) years of education, (3) race and ethnicity, and (5) fighting style (e.g., boxing, mixed martial arts, and martial arts). In the majority of cases, the male and female fighter matches were exact, but in a minority of matches, age and/or years of education was matched ±2 years secondary. Additionally, in a few cases, fighting style was not matched exactly (i.e., a purely MMA female fighter was matched with a male fighter who endorsed/practiced MMA 70% or greater of his time). There were no significant differences between male and female fighters with regard to age, years of education, ethnicity, and type of fighting (e.g., boxer, MMAs, MAs; all
The participants completed a short battery of computerized cognitive and motor tests, including symbol digit coding, finger-tapping, and Stroop-like tasks from the CNS Vital Signs program (
Beyond the CNS Vital Signs battery, the fighters completed six additional measures of cognitive functioning during assessment, including supplemental measures of processing speed [a timed reading passage and a computerized version of Trails A
Brain MRI scans were conducted on a MAGNETOM Verio 3-tesla scanner (Siemens Medical Systems, AG, Erlangen, Germany) with volumetric values derived from T1-weighted images
Volumetric segmentation was performed on the MPRAGE sequence using the Freesurfer, version 6.0, image analysis suite (
Conventional sagittal 3D magnetization-prepared rapid acquisition with gradient echo (MPRAGE) T1 [voxel size = 1 × 1 × 1.2 mm; flip angle/repetition time (TR)/echo time (TE)/inversion time (TI) = 9/2300/2.98/900 ms; scan time = 9:14] and axial turbo spin-echo T2 (voxel size = 0.8 × 0.8 × 4 mm; TR/TE =5,000/84 ms; 38 slices; scan time = 0:57).
Guided by prior findings from the PFBHS, as well as other studies highlighting structural and metabolic changes following repetitive head impact, the following brain regions were chosen
Analysis of variance tests were run to examine group differences between female and male fighters on the four CNS Vital Signs composite scores (verbal memory, processing speed, psychomotor speed, reaction time), as well as supplemental measures of processing speed (timed reading task, computerized version of Trails A), language (semantic fluency), and executive functioning (letter fluency, computerized version of Trails B). Analysis of covariance tests were run to examine group differences across regional brain volumes between male and female fighters while accounting for total brain volume. To assess the moderating role of sex in the relationship between fight exposure and regional brain volumes and cognitive performance, a series of within-subject moderation models was computed.
Twenty models were computed, one for each of the five bilateral brain regions identified
The fighters ranged in age from 19 to 55 years, with a mean age of 30.70 (SD = 6.7). Of the 110 fighters, 101 were active fighters consisting of 52 men and 49 women. Of the nine retired fighters, three were men and six were women. The participants were encouraged to select all race categories that applied to them. Self-defined race was 69% (
Participants' demographic data.
Age (mean, SD) | 30.7 (6.7) | 30.9 (6.9) | 30.6 (6.6) |
Education (mean, SD) | 14.0 (3.7) | 13.9 (3.7) | 14.2 (3.8) |
Number of professional fights (mean, SD) | 12.8 (15.8) | 12.4 (12.6) | 13.3 (18.5) |
Active fighters | 101 | 49 | 52 |
Boxers (%) | 32 (29.1) | 15 (27.3) | 17 (30.9) |
Mixed martial arts (%) | 69 (62.7) | 38 (69.1) | 31 (56.4) |
Martial arts (%) | 9 (8.2) | 2 (3.6) | 7 (12.7) |
Years of education completed | 108 | ||
Middle school (%) | 1 (0.9) | ||
Some high school (%) | 2 (1.9) | ||
High school (%) | 22 (20.4) | ||
Some college (%) | 8 (7.4) | ||
Associate's degree (%) | 31 (28.7) | ||
Bachelor's degree (%) | 36 (33.3) | ||
Some graduate school (%) | 1 (0.9) | ||
Master's degree (%) | 6 (5.6) | ||
Doctoral degree (%) | 1 (0.9) | ||
0 (%) | 21 (19.1) | ||
1–10 (%) | 39 (35.5) | ||
11–20 (%) | 27 (24.6) | ||
21–30 (%) | 13 (11.8) | ||
31–40 (%) | 5 (4.5) | ||
41–50 (%) | 0 | ||
51–60 (%) | 3 (2.7) | ||
61 or more (%) | 2 (1.8) |
ANCOVAs were conducted to assess differences in regional brain volumes while controlling for total brain volume. Female fighters (mean = 1,624.18 mm3) differed significantly from male fighters (mean = 1,669.05 mm3) in the left amygdala [
Male fighters had poorer performance on CNS Vital Signs psychomotor speed measures [
In order to explore the role of sex as a moderator of the relationship between fight exposure and regional brain volumes, a series of within-subject moderation analyses was computed according to the above-stated parameters. A significant moderation effect of sex was observed on the right hippocampus, right thalamus, left putamen, left amygdala, and right amygdala (please see
Relationship between the number of professional fights and the subcortical regional brain volumes (mm3) by sex:
Moderation effect of sex on subcortical regional brain volumes.
Right hippocampus | 0.015 | −6.10 | −10.95 to −1.25 | −15.37 | −3.17 |
Right thalamus | 0.020 | −13.45 | −24.70 to −2.21 | −30.60 | −3.69 |
Left putamen | 0.046 | −8.74 | −17.30 to −0.18 | −17.48 | −2.99 |
Left amygdala | 0.002 | −4.79 | −7.77 to −1.82 | −10.53 | −0.94 |
Right amygdala | 0.007 | −4.21 | −7.20 to −1.21 | −9.06 | −0.65 |
Right putamen | 0.015 | −8.68 | −10.95 to −1.25 | −16.62 | 0.73 |
While a significant moderation effect of sex was also observed on the right putamen, the relationship among women and men differed. Among male fighters, a higher number of professional fights was associated with a smaller right putamen volume. In contrast, greater right putamen volume was associated with a higher number of professional fights among female fighters (please see
A significant moderation effect of sex was also observed on CNS Vital Signs verbal memory and reaction time performance. While lower verbal memory performance was associated with a higher number of professional fights in male fighters, verbal memory performance was positively associated with the number of professional fights among female fighters (please see
Relationship between the number of professional fights and CNS Vital Signs performance by sex:
Moderation effect of sex on subcortical regional brain volumes.
CNS vital signs verbal memory | <0.0001 | −0.23 | −0.33 to −0.14 | −0.34 | 0.1262 |
CNS vital signs reaction time | 0.046 | 2.23 | −0.037 to 4.42 | 5.33 | 0.8708 |
Sex was not found to be a significant moderator in the relationship between the number of professional fights and performance on measures of processing speed (CNS Vital Signs processing speed, Trails A, timed reading task), psychomotor speed (CNS Vital Signs psychomotor speed), language (semantic fluency, word reading task), or executive functioning (letter fluency, Trails B; all
The current findings reveal key insights into sex-based differences among professional fighters for the relationship between NoPF and both regional brain volumes and cognitive performance. When accounting for whole brain volume, women were found to have a larger left amygdala than men. While prior research is equivocal, a recent meta-analysis suggests that the amygdalae are not sexually dimorphic (
With regard to regional brain volumes, relevant subcortical smaller volumes were associated with a greater number of professional fights among both male and female fighters. Notably, the relationship between the number of professional fights and regional brain volumes was observed to be much steeper in men. Interestingly, while a significant moderation effect of sex was observed on the right putamen, such that lower volumes in men were associated with a higher number of professional fights, an inverse relationship was observed among women. Notably, a level of noise exists in the measurement of regional brain volumes
Sex also moderated the relationship between the number of professional fights and two aspects of cognitive functioning, verbal memory and reaction time. Notably, a greater number of professional fights was associated with poorer verbal memory performance among male fighters, while an inverse relationship was observed among female fighters. Recent research has demonstrated that factors impacting hormones (e.g., use of hormonal contraceptives) in women younger than the age of 65 can have a profound impact on cognitive functioning, with the strongest association between verbal memory and hormonal contraceptive use (
While smaller regional brain volumes and poorer cognitive performance were largely associated with a higher number of professional fights in both men and women, female fighters were consistently less negatively impacted than male fighters. This may reflect lower velocity punches, greater resilience, or a combination of multiple factors. For example, Kimm and Thiel (
The current findings are further supported by prior PFBHS research outcomes that demonstrate volumetric reduction and negative impacts on cognitive performance with increased NoPF. One study using NoPF and years of fighting as a proxy for head injury exposure found that increased exposure was associated with decreased thalamic and caudate volumes as well as poorer processing speed performance (
Though the PFBHS is highly unique in that the data reflect a large cohort of professional fighters, various limitations of the current study must be considered. Less than 10% of the entire PFBHS sample is female. As the cohort of female fighters is significantly smaller than the cohort of male fighters, only baseline data could be considered in an effort to retain as many participants as possible and preserve statistical power. Notably, as the cohort of martial artists practice a wide variety of fighting styles (e.g., kickboxing, Muay Thai, taekwondo, and jiu-jitsu), the martial arts cohort may reflect a wide range of exposure to repetitive head impact. Similarly, NoPF only accounts for professional matches. As such, the impact of training for and participating in amateur matches is not considered. Additionally, rather than considering KO/TKO from professional matches alone, NoPF was utilized as a proxy for head impact exposure (inclusive of subconcussive and concussive impacts) across the period of training for and participating in professional level matches. Moreover, the fighters' weight classes were not considered but may impact the incidence and the severity of repetitive head impact. As approximately 40 analyses (some including covariates and multiple variables) were completed, an increased potential for false positives is acknowledged. One counterintuitive finding (i.e., larger putamen volumes among women with more exposure) was observed, indicating that additional research is required. Finally, additional unconsidered factors (i.e., drug use, socioeconomic status, genetic predisposition) may contribute to declines in cognitive functioning and regional brain volumes rather than exposure to repetitive head impact alone.
As the collection of data is ongoing, further analyses exploring changes over time when accounting for sex differences may provide insight into longer-term discrepancies in regional brain volumes and cognitive functioning. These baseline results do not necessarily imply differences in the long-term impacts of repetitive head impact as a function of sex, but longitudinal data over time comparing male and female fighters may have predictive value. Comparing male and female retired fighters may also provide some information about long-term concussive impact differences.
In summary, this study adds to our understanding that sex-based cognitive and volumetric differences in response to repetitive head impact exist among fighters. The main finding is that sex is an important moderator in the relationship between the number of professional fights, aspects of cognitive functioning, and brain volumes of numerous regions. While smaller regional brain volumes and poorer cognitive performance were generally associated with a greater number of professional fights among men and women, female fighters were consistently less negatively impacted than male fighters.
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
The studies involving human participants were reviewed and approved by Cleveland Clinic Institutional Review Board (#10-944). The patients/participants provided their written informed consent to participate in this study.
CB and SB designed the PFBHS. LB, SS, CB, and SB contributed to the design and execution of this project. LB, SS, CB, GS, and SB contributed to the analysis of the results and to the writing of the manuscript. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.