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, 2021 · DOI: https://doi.org/10.1016/j.ebiom.2021.103216 · Published: February 1, 2021

Simple Explanation

This study explores the relationship between changes in blood lipids and cognitive decline in older adults. It uses data from the Three-City study, a long-term study of older people in France. Researchers measured 189 different lipids in blood samples taken from participants who were free of dementia at the beginning of the study. They then followed these participants for 12 years to see who developed cognitive decline. The study found that specific lipid profiles in the blood were associated with a higher risk of cognitive decline. Specifically, lower levels of certain triglycerides and membrane lipids, and higher levels of another lipid, were linked to a greater likelihood of cognitive decline.

Study Duration

12 years

Participants

Discovery: n = 418, Validation: n = 314 older persons without dementia at baseline

Evidence Level

Level 2: Case-control study nested within a prospective cohort

Key Findings

1
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.
2
The identified lipid signature was largely dominated by polar lipids, including PC and short-chain PCO, a few PI and PE/PEO species, and the sphingomyelin SM40:2,2.
3
The lipid signature score was associated with greater cognitive decline in both discovery and validation stages.

Research Summary

This study aimed to identify a serum lipid signature associated with subsequent cognitive decline in the Three-City study. The researchers measured 189 serum lipids in a case-control sample nested within the Bordeaux study center and validated their findings in the Dijon study center. The study identified a signature of 17 lipids associated with cognitive decline, largely dominated by polar lipids. Lower levels of specific triglycerides and membrane lipids, and higher levels of another lipid, were associated with greater odds of cognitive decline. The 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.

Practical Implications

Early biomarker identification

The identified lipid signature could serve as an early biomarker for predicting cognitive decline in older adults.

Understanding pathophysiology

The findings may help reveal neuroplasticity-related pathways underlying cognitive aging and dementia.

Targeted interventions

Further research could explore the influence of specific exposures (e.g., nutrition) and the role of ApoE genotype on the identified lipid signature.

Study Limitations

1
Lipid measurements were only available at a single time-point.
2
Information on the fatty acid composition/position/family of all lipids was not available.
3
Moderate sample size may have yielded false negative results.

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