Diet‐Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort

• Published in: Molecular nutrition & food research Vol. 63; no. 18; pp. e1900177 - n/a
• Main Authors: Low, Dorrain Yanwen, Lefèvre‐Arbogast, Sophie, González‐Domínguez, Raúl, Urpi‐Sarda, 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, Andres‐Lacueva, Cristina, Thuret, Sandrine, Samieri, Cécilia, Manach, Claudine
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.09.2019; Wiley-VCH Verlag; John Wiley and Sons Inc
• Subjects: Aged; Aged, 80 and over; Aging; Apolipoprotein E; Arginine; Biomarkers; Blood - metabolism; Blood Chemical Analysis; Case-Control Studies; Cocoa; Coffea; Coffee; Cognitive ability; cognitive decline; Cognitive Dysfunction - blood; Cognitive Dysfunction - metabolism; Creatinine; Dementia - blood; Dementia - metabolism; Dementia disorders; Diabetes mellitus; Diet; dietary biomarkers; Eating; Education; Female; Fish; Fish Products; Food and Nutrition; Humans; Hydrocortisone; Life Sciences; Longitudinal Studies; Male; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Performance prediction; Prediction models; untargeted metabolomics; Wine; untargeted metabolomics; aging; cognitive decline; dietary biomarkers; coffee; Cognitive decline; Aging; Coffee; Dietary biomarkers; Untargeted metabolomics
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201900177

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. The Three‐City cohort of older persons with a 12‐year follow‐up for cognition is leveraged to identify, in the serum of initially non‐demented participants, metabolites associated with subsequent cognitive decline. Untargeted metabolomics reveals a signature of 22 metabolites improving cognitive decline prediction. It includes diet‐derived metabolites (e.g., from coffee, citrus juice, cocoa, fish), as well as endogenous metabolites responsive to diet.