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Diet‐Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort
Author(s) -
Low Dorrain Yanwen,
LefèvreArbogast Sophie,
GonzálezDomínguez Raúl,
UrpiSarda Mireia,
Micheau Pierre,
Petera Melanie,
Centeno Delphine,
Durand Stephanie,
PujosGuillot Estelle,
Korosi Aniko,
Lucassen Paul J,
Aigner Ludwig,
ProustLima Cécile,
Hejblum Boris P,
Helmer Catherine,
AndresLacueva Cristina,
Thuret Sandrine,
Samieri Cécilia,
Manach Claudine
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201900177
Subject(s) - metabolomics , cognitive decline , metabolome , metabolite , dementia , prospective cohort study , biomarker , cognition , european prospective investigation into cancer and nutrition , medicine , effects of sleep deprivation on cognitive performance , physiology , endocrinology , biology , bioinformatics , biochemistry , disease , psychiatry
Scope Untargeted metabolomics may reveal preventive targets in cognitive aging, including within the food metabolome. Methods and results A case‐control study nested in the prospective Three‐City study includes participants aged ≥65 years and initially free of dementia. A total of 209 cases of cognitive decline and 209 controls (matched for age, gender, education) with slower cognitive decline over up to 12 years are contrasted. Using untargeted metabolomics and bootstrap‐enhanced penalized regression, a baseline serum signature of 22 metabolites associated with subsequent cognitive decline is identified. The signature includes three coffee metabolites, a biomarker of citrus intake, a cocoa metabolite, two metabolites putatively derived from fish and wine, three medium‐chain acylcarnitines, glycodeoxycholic acid, lysoPC(18:3), trimethyllysine, glucose, cortisol, creatinine, and arginine. Adding the 22 metabolites to a reference predictive model for cognitive decline (conditioned on age, gender, education and including ApoE‐ε4, diabetes, BMI, and number of medications) substantially increases the predictive performance: cross‐validated Area Under the Receiver Operating Curve = 75% [95% CI 70–80%] compared to 62% [95% CI 56–67%]. Conclusions The untargeted metabolomics study supports a protective role of specific foods (e.g., coffee, cocoa, fish) and various alterations in the endogenous metabolism responsive to diet in cognitive aging.