Biological Markers of Cognitive Impairments in Combat and Contact-Sport Athletes: A Systematic Review

This systematic review investigated the direct association between biomarkers and cognitive performance in adult athletes exposed to repetitive head impacts. Searches in the APA PsycNet, PubMed, Google Scholar, CAPES, and BVSalud databases (11 April 2026) evaluated adult athletes (≥18 years) who used standardized neuropsychological tests and analyzed the association between biomarkers and cognition. Two reviewers performed selection, data extraction, and risk-of-bias assessment. Certainty of evidence was assessed using an adapted GRADE framework. A total of 10,480 records were identified. After removal of 697 duplicate records, they underwent screening and eligibility assessment, resulting in the inclusion of 10 studies. They showed low risk of bias, but sample imprecision reduced the certainty of evidence in 50% of cases. The cognitive domains assessed were memory, attention, processing speed, reaction time, and executive functions. Axonal biomarkers (70% of studies), inflammatory (40%), and synaptic biomarkers (10%). Eighty percent of the studies found a relationship between biological alterations and cognition. The most promising biomarkers associated with cognitive deficits are NfL and GFAP, but due to high methodological heterogeneity, imprecision of estimates (GRADE), and biases, the conclusions are provisional. Caution is recommended in clinical application until prospective studies with larger samples and active control groups confirm the findings.