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<div> Inter-individual cognitive variability, influenced by genetic and environmental factors, is crucial for understanding typical cognition and identifying early cognitive disorders. This study investigated the association between serum protein expression profiles and cognitive variability in a healthy Thai population using machine learning algorithms. We included 199 subjects, aged 20 to 70, and measured cognitive performance with the Wisconsin Card Sorting Test. Differentially expressed proteins (DEPs) were identified using label-free proteomics and analyzed with the Linear Model for Microarray Data. We discovered 213 DEPs between lower and higher cognition groups, with 155 upregulated in the lower cognition group and enriched in the IL-17 signaling pathway. Subsequent bioinformatic analysis linked these DEPs to neuroinflammation-related cognitive impairment. A random forest model classified cognitive ability groups with an accuracy of 81.5%, sensitivity of 65%, specificity of 85.9%, and an AUC of 0.79. By targeting a specific Thai cohort, this research provides novel insights into the link between neuroinflammation and cognitive performance, advancing our understanding of cognitive variability, highlighting the role of biological markers in cognitive function, and contributing to developing more accurate machine learning models for diverse populations. </div>