Background

Metabolomics study provides an opportunity to identify novel molecular determinants of altered cognitive function.

Methods

During 2013 to 2016 Bogalusa Heart Study (BHS) visit, 1,177 participants underwent untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy metabolomics profiling. Global cognition and five cognition domains were also assessed. The cross-sectional associations of single metabolites with cognition were tested using multiple linear regression models. Weighted correlation network analysis was used to examine the covariable-adjusted correlations of modules of co-abundant metabolites with cognition. Analyses were conducted in the overall sample and according to both ethnicity and sex.

Results

Five known metabolites and two metabolite modules robustly associated with cognition across overall and stratified analyses. Two metabolites were from lipid sub-pathways including fatty acid metabolism [9-hydroxystearate; minimum P-value (min-P)=1.11×10^-5], and primary bile acid metabolism (glyco-alpha-muricholate; min-P=4.10×10^-5). One metabolite from the glycogen metabolism sub-pathway (maltose; min-P=9.77×10^-6), one from the polyamine metabolism sub-pathway (N-acetyl-isoputreanine; min-P=1.03×10^-5), and one from the purine metabolism sub-pathway (7-methylguanine; min-P=1.19×10^-5) were also identified. Two metabolite modules reflecting bile acid metabolism and androgenic steroids correlated with cognition (min-P=5.00×10^-4 and 3.00×10^-3, respectively).

Conclusion

The novel associations of 5 known metabolites and 2 metabolite modules with cognition provide insights into the physiological mechanisms regulating cognitive function.