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Diet-Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort Low, Dorrain Yanwen Lefèvre Arbogast, Sophie González-Domínguez, Raúl Urpí Sardà, Mireia Micheau, Pierre Petera, Melanie Centeno, Delphine Durand, Stephanie Pujos Guillot, Estelle Korosi, Aniko Lucassen, Paul J. Aigner, Ludwig Proust Lima, Cécile Hejblum, Boris P. Helmer, Catherine Andrés Lacueva, Ma. Cristina Thuret, Sandrine Samieri, Cécilia Manach, Claudine Metabòlits Dieta Metabolites Diet 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, gen- der, 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. 2020-04-28T09:10:05Z 2020-06-20T05:10:23Z 2019-06-20 2020-04-28T09:10:05Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 1613-4125 https://hdl.handle.net/2445/157803 691806 31218777 eng Versió postprint del document publicat a: https://doi.org/10.1002/mnfr.201900177 Molecular Nutrition & Food Research, 2019, vol. 63, p. 1900177 https://doi.org/10.1002/mnfr.201900177 (c) Wiley-VCH, 2019 info:eu-repo/semantics/openAccess 10 p. application/pdf Wiley-VCH Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)