Heading and Soccer: understanding cognitive risks, benefits, and the potential mediating role of white matter

PROJECT SUMMARY/ABSTRACT A key goal of “Healthy People 2030” is to improve the health of adults through aerobic physical activity. Soccer, the most popular sport on earth, is an aerobic outlet for more than 25 million Americans. The potential benefits of soccer are offset by repetitive subconcussive head impacts (RSHI) from soccer heading. RSHI are associated with exposure-dependent adverse effects on neuroimaging and on cognitive performance, independent of collisions and concussion. The tradeoffs between aerobic benefits and RSHI-related harms are not known. The central aim of this proposal is to examine the aerobic benefits of soccer play, in relation to RSHI harms, for brain structure and function, and to explore person-level factors that modify this risk-benefit tradeoff. Beneficial effects of aerobic capacity and adverse subclinical effects of RSHI can be detected with neuroimaging of white matter. However, little is known about their joint impact on white matter and, in turn, how white matter features mediate effects on cognitive function. Fundamental knowledge on the RSHI risk-benefit balance can inform our understanding of RSHI morbidity and its mitigation beyond the specific context of soccer, such as other sports and combat. Prior work on RSHI effects has not specifically measured aerobic capacity, and little is known about whether and how white matter mediates exposure-outcome associations. Our proposed 2-year longitudinal follow up study of 280 young adults, including soccer players with high (n=70) and low (n=70) exposure to RSHI, non-collision athletes (n=70) and non-athlete controls (n=70), will test the hypothesis that aerobic capacity-engendered benefits confound and modify the adverse effects of RSHI on white matter that, in turn, is a mediator of adverse cognitive effects. We will measure aerobic capacity (VO2max) and RSHI over 2 years and perform Myelin Water and Microstructure MRI of white matter as well as cognitive assessments, at enrollment and 2 years later. We will address the following specific aims: Aim 1: Evaluate the joint effects of VO2max and RSHI on white matter myelination and microstructure. Aim 2: Assess mediation by white matter of the known associations of VO2max and RSHI with cognitive performance. Aim 3: Explore the BDNF-Val66met and ApoE-ε4 gene variants as modifiers of the tradeoff of VO2max and RHSI-mediated effects on white matter. Delineating risk vs. benefit to cognitive performance from soccer can transform perception of risk by stakeholders, facilitate choice and guidance on soccer participation and heading. Choices that impact young adult players, with high RSHI exposure and decades of future needs, have the potential to impact their wellbeing, healthcare footprint and productivity for decades.