Song Joan Y, Fleysher Roman, Ye Kenny, Kim Mimi, Stewart Walter F, Zimmerman Molly E, Lipton Richard B, Lipton Michael L
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York.
Department of Radiology, Columbia University Irving Medical Center, New York, New York.
JAMA Netw Open. 2025 Sep 2;8(9):e2532461. doi: 10.1001/jamanetworkopen.2025.32461.
Sport-related repetitive head impacts (RHIs) are linked to structural and functional brain changes and may be associated with risk for neurodegenerative disease. However, the locus of RHI-associated pathology that leads to adverse cognitive performance has yet to be characterized in vivo.
To examine whether orbitofrontal gray matter-white matter interface (GWI) microstructure is associated with soccer RHI and whether it mediates the association of RHI with cognitive performance.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study, performed at Albert Einstein College of Medicine and Columbia University Irving Medical Center, included a population-based sample from the greater New York City area of amateur soccer players aged 18 to 55 years who played for at least 5 years, currently played at least 6 months per year, and were fluent in English. Exclusion criteria consisted of schizophrenia, bipolar disorder, current substance use disorder, any drug use within 30 days, and any contraindication to magnetic resonance imaging. Data were collected from November 11, 2013, to December 28, 2015, and analyses were performed from April 1 through December 4, 2024.
Soccer RHI exposure in the prior 12 months quantified via the HeadCount 12-month survey.
Slope of diffusion magnetic resonance imaging metrics (fractional anisotropy [FA], axial diffusivity, orientation dispersion index, and intracellular volume fraction) across the GWI was computed for each of 6 cerebral regions (cingulate, orbitofrontal, frontal, temporal, parietal, and occipital). The GWI slope association with RHI and with International Shopping List (ISL) immediate recall task performance, which is associated with RHI, were examined. Mediation analyses tested for the mechanistic role of GWI slope in the RHI and ISL association.
In 352 adult amateur soccer players aged 18 to 53 years (243 [69.0%] male; mean [SD] age, 25.6 [7.5] years), greater RHI exposure was associated with a less steep FA slope across the orbitofrontal GWI (estimate, 0.000001; P < .001). The orbitofrontal FA slope measure mediated the association of RHI with ISL performance (indirect effect estimate, -0.000064; P = .006).
In this cross-sectional study of soccer RHI, the orbitofrontal GWI emerged as a specific site of soccer RHI-related consequences, with FA slope suggesting that GWI microstructural disruption plays a mediating role in the association of greater RHI exposure with poorer verbal learning task performance.
