Characterization of a metabolomics signature of the brain-health-promoting MIND diet in older persons - 12/09/26

Doi : 10.1016/j.tjpad.2026.100670

Jeanne Neuffer ^a,^b,^⁎ , Raúl González-Domínguez ^c,^d, Sophie Lefèvre-Arbogast ^a, Dorrain Y Low ^e,^f, Alba Tor-Roca ^c,^d, Catherine Helmer ^a, Andrea Du Preez ^g, Chiara de Lucia ^h, Silvie R. Ruigrok ⁱ, Barbara Altendorfer ^j, Ludwig Aigner ^j, Paul J Lucassen ^i,^k, Aniko Korosi ⁱ, Sandrine Thuret ^h, Claudine Manach ^e, Mercè Pallàs ^l, Alex Sánchez-Pla ^c,^d, Cristina Andres-Lacueva ^c,^d, Mireia Urpi-Sarda ^c,^d, Cécilia Samieri ^a

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

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

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

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

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

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

^g 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

^h 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

ⁱ Brain Plasticity Group, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands

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

^k The Center for Urban Mental Health, University of Amsterdam, the Netherlands

^l 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 at: University Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, F-91120, Palaiseau, France. University Paris-Saclay AgroParisTech, INRAE, UMR PNCA Palaiseau F-91120 France

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, 24 h 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