Biomarkers of Fatigue: Metabolomics Profiles Predictive of Cognitive Performance.

摘要

Cognitive performance and fatigue are well known to be inversely related. Continuous and sustained actions in operational environments typically lead to reduced sleep normally required to perform optimally. These operational environments subject the warfighter to intense physical and mental exertion. Because fatigue continues to be an occupational hazard, leading to cognitive defects in performance, there has been a recognized need for real-time detection technologies that minimize fatigue-induced mishaps. In the current study, 23 subjects were subjected to 36 h of sleep deprivation and cognitive psychomotor vigilance and automated neuropsychological assessment metric tests were conducted over the last 24 h of sleep deprivation. In addition, urine was collected prior to and over the course of the cognitive testing period for metabolite analysis using nuclear magnetic resonance (NMR) spectroscopy. Bioinformatics analysis of the NMR data identified 23 spectral resonances associated with specific urinary metabolites that could be used to classify subject fatigue susceptibility 12 h prior to cognitive testing and at 28 h of sleep deprivation on cognitive testing. Of these, 14 were found to statistically significant when associated with testing cognitive performance. A majority of these metabolites appeared to be associated with nutritional status and suggested that observed increases in dietary protein intake prior to cognitive testing led to increased cognitive performance when sleep deprived. NMR data were also found to correlate with previously reported psychological testing results of these same subjects. Taken together, our results indicate that a subset of urinary metabolites may provide a useful noninvasive biomarker screen for mission performance and readiness during sustained, demanding missions.