期刊
EBIOMEDICINE
卷 64, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ebiom.2021.103216
关键词
Cognitive dysfunction; Dementia; Membrane lipids; Metabolomics; Lipidomics; Serum biomarker
资金
- Fondation pour la Recherche Medicale
- Caisse Nationale Maladie des Travailleurs Salaries
- Direction Generale de la Sante
- Mutuelle Generale de l'Education Nationale
- Institut de la Longevite
- Regional Government of Aquitaine
- Regional Government of Bourgogne
- Ministry of Research-INSERM Programme Cohortes et collections de donnees biologiques
- French National Research Agency [COGINUT ANR-06-PNRA-005]
- Fondation Plan Alzheimer [FCS 2009-2012]
- Caisse Nationale pour la Solidarite et l'Autonomie (CNSA)
- JPI-HDHL [ANR-15-HDHL0002-05, PCIN-2015-229-MINECO]
- JPI-HDHL (Medical Research Council UK) [MR/N030087/1]
- JPI-HDHL (CiberFES-FEDER) [2017SGR1546]
- JPI-HDHL (ICREA Academia Award from the Generalitat de Catalunya)
- Juan de la Cierva program from MINECO [FJCI-2015-26590]
- NWO
- Alzheimer Nederland
- UvA Urban Mental Health program
- French National Research Agency (ANR) [17-EURE0019]
- Fondation de France
- MRC [MR/N030087/1] Funding Source: UKRI
This study found that a specific profile of lipids involved in membrane fluidity, myelination, and lipid rafts in the blood lipidome of non-demented older persons is associated with subsequent cognitive decline.
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. (C) 2021 The Authors. Published by Elsevier B.V.
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