Characterization of a metabolomics signature of the brain-health-promoting MIND diet in older persons - 05/09/26

Doi : 10.1016/j.tjpad.2026.100670

Jeanne Neuffer ^1,^2,^⁎ , Raúl González-Domínguez ^3,⁴, Sophie Lefèvre-Arbogast ¹, Dorrain Y Low ^5,⁶, Alba Tor-Roca ^3,⁴, Catherine Helmer ¹, Andrea Du Preez ⁷, Chiara de Lucia ⁸, Silvie R. Ruigrok ⁹, Barbara Altendorfer ¹⁰, Ludwig Aigner ¹⁰, Paul J Lucassen ^9,¹¹, Aniko Korosi ⁹, Sandrine Thuret ⁸, Claudine Manach ⁵, Mercè Pallàs ¹², Alex Sánchez-Pla ^3,⁴, Cristina Andres-Lacueva ^3,⁴, Mireia Urpi-Sarda ^3,⁴, Cécilia Samieri ¹

¹ University of Bordeaux, Inserm Bordeaux Population Health Research Center, UMR 1219, F-33000 Bordeaux, France

² University Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, F-91120 Palaiseau, France

³ and Gastronomy Department, Institute of Nutrition and Food Safety (INSA-UB), Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain

⁴ CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain

⁵ University Clermont Auvergne, INRAE, UMR1019, Human Nutrition Unit, F-63000 Clermont Ferrand, France

⁶ Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore

⁷ Department of Nutritional Sciences, School of Life Course & Population Sciences, Faculty of Life Sciences & Medicine, King’s College London, 150 Stamford Street, London SE1 9NH, UK

⁸ Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 9NU, UK

⁹ Brain Plasticity Group, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands

¹⁰ Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg 5020, Austria

¹¹ The Center for Urban Mental Health, University of Amsterdam, The Netherlands

¹² Pharmacology Section, Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Neurociencies, University of Barcelona, E-08028, Barcelona, Spain

^⁎ Corresponding author. Jeanne Neuffer, PhD, University Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, F-91120 Palaiseau, France, Phone +33186100855 University Paris-Saclay AgroParisTech, INRAE, UMR PNCA, F-91120 Palaiseau France

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Abstract

Background

The MIND diet supports healthy cognitive aging. Yet, a challenge remains to identify individuals who do not adhere to the MIND and could be at risk for accelerated cognitive decline. A multi-metabolite biomarker panel could facilitate population screening.

Objectives

To determine and validate a blood metabolomics signature of MIND adherence in a large cohort of older adults, and to estimate its association with subsequent cognitive decline.

Design, Setting and Participants

Participants were older adults (≥65 years) from the population-based three-City (3C) cohort, free of dementia at study baseline and followed for up to 12 years for cognition, who were included in two case-control samples on cognitive decline nested within two centers (Bordeaux and Dijon cities, n=838).

Exposures

155 diet-related serum metabolites measured with a multianalyte metabolomics platform.

Main outcomes and measurements

The primary outcome was adherence to the MIND diet, assessed in a subsample of 344 participants from Bordeaux center (which underwent the dietary surveys, 24h recall and food-frequency questionnaire). A metabolomics signature of MIND diet adherence was characterized with penalized regression and a metabolomics score (“metaboscore”) reflecting the overall MIND biological fingerprint was calculated. The secondary outcome was cognitive decline status (coded as binary: accelerated, vs. null or minimal decline) over follow-up, assessed using repeated cognitive measures in the two case-control samples. The metaboscore was reconstructed and linked to the odds of cognitive decline.

Results

Eight metabolites were identified: three were associated with higher MIND adherence (3-hydroxyhippuric acid, 5-hydroxyindole-3-acetic acid, betaine - phenolic acids and amino acid related to plant foods) and five with lower MIND adherence (1-methylhistidine from red meat; cyclo(L-leucyl-L-prolyl) from coffee; tartaric acid from wine; myristoyl-carnitine and dehydroepiandrosterone sulfate, endogenous). The French-MIND metaboscore was linked to lower odds of cognitive decline, although replication was not statistically significant after multivariable adjustment.

Conclusion

A novel metabolomic signature of the MIND diet was characterized, which may help screen older adults at risk of poor brain nutrition and could support personalized dietary prevention strategies.

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Keywords : Cognitive decline, Metabolomics, MIND diet, Diet