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

ABSTRACT: 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-?4, 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.

SUBMITTER: Low DY

PROVIDER: S-EPMC6790579 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

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 Lucassen Paul J PJ Aigner Ludwig L Proust-Lima Cécile C Hejblum Boris P BP Helmer Catherine C Andres-Lacueva Cristina C Thuret Sandrine S Samieri Cécilia C Manach Claudine C

Molecular nutrition & food research 20190709 18

<h4>Scope</h4>Untargeted metabolomics may reveal preventive targets in cognitive aging, including within the food metabolome.<h4>Methods and results</h4>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 ...[more]

PMID: 31218777

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Project description:Background & aimsLow-grade inflammation appears to play an etiological role in cognitive decline. However the association between an inflammatory dietary pattern and cognitive decline has not been investigated. We aimed to investigate dietary patterns associated with inflammation and whether such diet is associated with cognitive decline.MethodsWe analyzed 5083 participants (28.7% women) from the Whitehall II cohort study. Diet and serum interleukin-6 (IL-6) were assessed in 1991-1993 and 1997-1999. We used reduced rank regression methods to determine a dietary pattern associated with elevated IL-6. Cognitive tests were performed in 1997-1999 and repeated in 2002-2004 and 2007-2009. The association between dietary pattern and cognitive decline between ages 45 and 79 was assessed using linear mixed models.ResultsWe identified an inflammatory dietary pattern characterized by higher intake of red meat, processed meat, peas and legumes, and fried food, and lower intake of whole grains which correlated with elevated IL-6 both in 1991-1993 and 1997-1999. A greater decline in reasoning was seen in participants in the highest tertile of adherence to the inflammatory dietary pattern (-0.37 SD; 95% confidence interval [CI] -0.40, -0.34) compared to those in the lowest tertile (-0.31; 95% CI -0.34, -0.28) after adjustment for age, sex, ethnicity, occupational status, education, and total energy intake (p for interaction across tertiles = 0.01). This association remained significant after multivariable adjustment. Similarly for global cognition, the inflammatory dietary pattern was associated with faster cognitive decline after multivariable adjustment (p for interaction across tertiles = 0.04). Associations were stronger in younger participants (<56 years), reducing the possibility of reverse causation.ConclusionsOur study found that a dietary pattern characterized as higher intake of red and processed meat, peas, legumes and fried food, and lower intake of whole grains was associated with higher inflammatory markers and accelerated cognitive decline at older ages. This supports the case for further research.

Dataset Information

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

Publications

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

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