Early signature in the blood lipidome associated with subsequent cognitive decline in the elderly: A case-control analysis nested within the Three-City cohort study
Sophie Lefèvre-Arbogast,
Boris P Hejblum,
Catherine Helmer,
Christian Klose,
Claudine Manach,
Dorrain Y Low,
Mireia Urpi-Sarda,
Cristina Andres-Lacueva,
Raúl González-Domínguez,
Ludwig Aigner,
Barbara Altendorfer,
Paul J Lucassen,
Silvie R Ruigrok,
Chiara De Lucia,
Andrea Du Preez,
Cécile Proust-Lima,
Sandrine Thuret,
Aniko Korosi,
Cécilia Samieri
Affiliations
Sophie Lefèvre-Arbogast
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France
Boris P Hejblum
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France; Inria SISTM, Bordeaux Sud-Ouest, Bordeaux 33000, France
Catherine Helmer
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France
University of Clermont Auvergne, INRA, UMR1019, Human Nutrition Unit, Clermont Ferrand 63000, France
Dorrain Y Low
University of Clermont Auvergne, INRA, UMR1019, Human Nutrition Unit, Clermont Ferrand 63000, France
Mireia Urpi-Sarda
Nutrition, Food Science and Gastronomy Department, Faculty of Pharmacy and Food Science, CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, University of Barcelona, Barcelona 08028, Spain
Cristina Andres-Lacueva
Nutrition, Food Science and Gastronomy Department, Faculty of Pharmacy and Food Science, CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, University of Barcelona, Barcelona 08028, Spain
Raúl González-Domínguez
Nutrition, Food Science and Gastronomy Department, Faculty of Pharmacy and Food Science, CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, University of Barcelona, Barcelona 08028, Spain
Ludwig Aigner
Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg 5020, Austria
Barbara Altendorfer
Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg 5020, Austria
Paul J Lucassen
Brain Plasticity Group, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam 1098 XH, Netherlands
Silvie R Ruigrok
Brain Plasticity Group, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam 1098 XH, Netherlands
Chiara De Lucia
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9NU, United Kingdom
Andrea Du Preez
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9NU, United Kingdom
Cécile Proust-Lima
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France
Sandrine Thuret
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9NU, United Kingdom; Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
Aniko Korosi
Brain Plasticity Group, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam 1098 XH, Netherlands
Cécilia Samieri
University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France; Corresponding author. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, 33076 Bordeaux cedex, France
Background: Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level. Methods: We studied participants from the Three-City study, a multicentric cohort of older persons, free of dementia at time of blood sampling, and who provided repeated measures of cognition over 12 subsequent years. We measured 189 serum lipids from 13 lipid classes using shotgun lipidomics in a case-control sample on cognitive decline (matched on age, sex and level of education) nested within the Bordeaux study center (discovery, n = 418). Associations with cognitive decline were investigated using bootstrapped penalized regression, and tested for validation in the Dijon study center (validation, n = 314). Findings: Among 17 lipids identified in the discovery stage, lower levels of the triglyceride TAG50:5, and of four membrane lipids (sphingomyelin SM40:2,2, phosphatidylethanolamine PE38:5(18:1/20:4), ether-phosphatidylethanolamine PEO34:3(16:1/18:2), and ether-phosphatidylcholine PCO34:1(16:1/18:0)), and higher levels of PCO32:0(16:0/16:0), were associated with greater odds of cognitive decline, and replicated in our validation sample. Interpretation: These findings indicate that in the blood lipidome of non-demented older persons, a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts, is associated with subsequent cognitive decline. Funding: The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.
