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Aging (Albany NY). 2019 Jul 21;11(14):5124-5139. doi: 10.18632/aging.102107.

Novel serum metabolites associate with cognition phenotypes among Bogalusa Heart Study participants.

Author information

1
Department of Epidemiology, Tulane University, New Orleans, LA 70112, USA.
2
Institute of Clinical Medical Science, China-Japan Friendship Hospital, National Clinical Research Center of Respiratory Diseases, Beijing, China.
3
Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA 30602, USA.
4
Children's Minnesota Research Institute, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.
5
School of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
6
Metabolon, Inc., Durham, NC 27560, USA.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; cognition; dementia; metabolite network; metabolomics

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