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
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 ti...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421000098 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sophie Lefèvre-Arbogast |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T15:01:44Z |
| format | Article |
| id | doaj.art-4ee2264573804790a371533b89baef44 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-14T15:01:44Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-4ee2264573804790a371533b89baef442022-12-21T22:56:48ZengElsevierEBioMedicine2352-39642021-02-0164103216Early signature in the blood lipidome associated with subsequent cognitive decline in the elderly: A case-control analysis nested within the Three-City cohort studySophie Lefèvre-Arbogast0Boris P Hejblum1Catherine Helmer2Christian Klose3Claudine Manach4Dorrain Y Low5Mireia Urpi-Sarda6Cristina Andres-Lacueva7Raúl González-Domínguez8Ludwig Aigner9Barbara Altendorfer10Paul J Lucassen11Silvie R Ruigrok12Chiara De Lucia13Andrea Du Preez14Cécile Proust-Lima15Sandrine Thuret16Aniko Korosi17Cécilia Samieri18University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, FranceUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France; Inria SISTM, Bordeaux Sud-Ouest, Bordeaux 33000, FranceUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, FranceLipotype GmbH, Tatzberg 47, Dresden 01307, GermanyUniversity of Clermont Auvergne, INRA, UMR1019, Human Nutrition Unit, Clermont Ferrand 63000, FranceUniversity of Clermont Auvergne, INRA, UMR1019, Human Nutrition Unit, Clermont Ferrand 63000, FranceNutrition, 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, SpainNutrition, 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, SpainNutrition, 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, SpainInstitute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg 5020, AustriaInstitute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg 5020, AustriaBrain Plasticity Group, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam 1098 XH, NetherlandsBrain Plasticity Group, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam 1098 XH, NetherlandsDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9NU, United KingdomDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 9NU, United KingdomUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, FranceDepartment 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, GermanyBrain Plasticity Group, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam 1098 XH, NetherlandsUniversity 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, FranceBackground: 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.http://www.sciencedirect.com/science/article/pii/S2352396421000098Cognitive dysfunctionDementiaMembrane lipidsMetabolomicsLipidomicsSerum biomarker |
| spellingShingle | 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 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 EBioMedicine Cognitive dysfunction Dementia Membrane lipids Metabolomics Lipidomics Serum biomarker |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Cognitive dysfunction Dementia Membrane lipids Metabolomics Lipidomics Serum biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2352396421000098 |
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