Diet-Related Metabolites Associated with Cognitive Decline Revealed by Untargeted Metabolomics in a Prospective Cohort.
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.
['Low|Dorrain Yanwen|DY|', 'Lefèvre-Arbogast|Sophie|S|', 'González-Domínguez|Raúl|R|', 'Urpi-Sarda|Mireia|M|', 'Micheau|Pierre|P|', 'Petera|Melanie|M|', 'Centeno|Delphine|D|', 'Durand|Stephanie|S|', 'Pujos-Guillot|Estelle|E|', 'Korosi|Aniko|A|0000-0001-9701-3331', 'Lucassen|Paul J|PJ|', 'Aigner|Ludwig|L|', 'Proust-Lima|Cécile|C|', 'Hejblum|Boris P|BP|', 'Helmer|Catherine|C|', 'Andres-Lacueva|Cristina|C|0000-0002-8494-4978', 'Thuret|Sandrine|S|', 'Samieri|Cécilia|C|', 'Manach|Claudine|C|0000-0003-1094-3363']
D000368:Aged D000369:Aged, 80 and over D001769:Blood D001774:Blood Chemical Analysis D016022:Case-Control Studies D040503:Coffea D060825:Cognitive Dysfunction D003704:Dementia D004032:Diet D004435:Eating D005260:Female D005396:Fish Products D006801:Humans D008137:Longitudinal Studies D008297:Male D055432:Metabolomics
cognitive decline untargeted metabolomics aging coffee dietary biomarkers