University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo-Saignat, Bordeaux 33076, France.
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.
EBioMedicine. 2021 Feb;64:103216. doi: 10.1016/j.ebiom.2021.103216. Epub 2021 Jan 25.
Brain lipid metabolism appears critical for cognitive aging, but whether alterations in the lipidome relate to cognitive decline remains unclear at the system level.
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).
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.
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.
The complete list of funders is available at the end of the manuscript, in the Acknowledgement section.
脑脂质代谢似乎对认知衰老至关重要，但脂质组的改变是否与认知能力下降有关，在系统水平上仍不清楚。
我们研究了来自三城研究的参与者，这是一个多中心的老年人队列，在采血时没有痴呆症，并且在随后的 12 年内提供了认知的重复测量。我们使用 shotgun 脂质组学在 Bordeaux 研究中心（发现，n=418）内对认知衰退（按年龄、性别和教育程度匹配）的病例对照样本中测量了 13 个脂质类别的 189 种血清脂质。使用 bootstrap 惩罚回归研究了与认知衰退的关联，并在 Dijon 研究中心（验证，n=314）进行了验证。
在发现阶段确定的 17 种脂质中，较低水平的甘油三酯 TAG50:5，以及四种膜脂质（鞘磷脂 SM40:2,2、磷脂酰乙醇胺 PE38:5(18:1/20:4)、醚磷脂酰乙醇胺 PEO34:3(16:1/18:2)和醚磷脂酰胆碱 PCO34:1(16:1/18:0)），以及更高水平的 PCO32:0(16:0/16:0)，与认知衰退的几率增加有关，并在我们的验证样本中得到复制。
这些发现表明，在非痴呆老年人的血液脂质组中，涉及膜流动性、髓鞘形成和脂质筏的特定脂质谱与随后的认知衰退有关。
完整的资助者名单可在文末的Acknowledgement 部分找到。
