Effects of Lifetime Exposure to Sports-Related Head Impacts on Brain Injury and Inflammatory Blood Biomarkers Among Former Middle-Aged Athletes

Repetitive head impacts from contact sports are associated with an increased risk of neurodegenerative conditions. While studies have examined acute and chronic outcomes in young and deceased athletes, research on middle-aged former athletes remains limited. We employed multiplex biomarker approaches to examine whether brain injury and systemic inflammatory blood biomarkers are reflective of ≥10 years of participation in contact sports in retired, middle-aged amateur athletes. This cross-sectional study included a cohort of 41 former contact athletes (32 male, 9 female) and 22 age- and sex-matched noncontact athletes (14 male, 8 female). Blood biomarkers of brain injury, including glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 (UCH-L1), tau, and neurofilament light (NfL), alongside 18 systemic inflammatory markers, were examined via linear regression models with age and concussion history as covariates. Our analyses revealed no significant differences in brain injury blood biomarkers between groups. However, increasing age was associated with increased NfL levels in contact athletes, while greater concussion history correlated with elevated UCH-L1 and tau in contact athletes only. Contact athletes exhibited significantly increased levels of systemic inflammatory markers, including IL-8, CCL-2, CCL-3, IL-2, VCAM-1, and S100B. While brain injury blood biomarkers did not differ between groups, the association between age, concussion history, and increased NfL, UCH-L1, and tau levels in the contact group suggests potential long-term neural consequences of repetitive head impacts. Elevated systemic inflammatory markers potentially highlight a chronic inflammatory response in former contact athletes, underscoring the need for continued monitoring and interventions to mitigate neurodegenerative risk.