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. 2020 Jun 9:18:1613-1624.
doi: 10.1016/j.csbj.2020.06.001. eCollection 2020.

Plasma lipidomic biomarker analysis reveals distinct lipid changes in vascular dementia

Yue Liu  1 , Daniel K Y Chan  2 , Anbupalam Thalamuthu  1   3 , Wei Wen  1 , Jiyang Jiang  1 , Matthew Paradise  1 , Teresa Lee  1 , John Crawford  1 , Matthew Wai Kin Wong  1 , Ying Hua Xu  2 , Anne Poljak  4   5 , Russell Pickford  4 , Perminder S Sachdev  1   6 , Nady Braidy  1
Affiliations

Plasma lipidomic biomarker analysis reveals distinct lipid changes in vascular dementia

Yue Liu et al. Comput Struct Biotechnol J. .

Abstract

Vascular dementia (VaD) is a complex neurocognitive disorder secondary to a variety of cerebrovascular lesions. Numerous studies have shown that lipid metabolism is involved in the pathobiology of the disease. We examined the plasma lipid profiles in VaD, with the expectation of identifying reliable lipid biomarkers for VaD. 49 VaD patients and 48 healthy controls were recruited from Bankstown-Lidcombe Hospital in Sydney, Australia. Lipids were extracted by single phase 1-butanol/methanol, and untargeted analysis was performed by liquid chromatography coupled-mass spectrometry (LC-MS/MS). Univariate analysis of variance was used to examine the differences in lipid classes and individual lipids between VaD and control groups. In an independent sample of 161 subjects from the Older Australian Twins Study (OATS), elastic net penalization for the generalized linear model (Glmnet) and Random Forest were applied to the lipid levels to subcategorise the sample into vascular cognitive impairment and controls. Most lipids belonging to the classes of ceramides (Cer), cholesterol esters (ChE) and phospholipids were significantly lower in VaD plasma, while glycerides were elevated compared to controls. Levels of ChE, Cer and the two lipid classes together achieved the best accuracy in discriminating VaD from controls, with more than 80% accuracy. The probable VaD group in the OATS sample predicted by the lipid levels showed greater impairment in most cognitive domains, especially attention and processing speed and executive function from controls but did not differ in white matter hyperintensities and DTI measures. As a conclusion, plasma lipids levels, in particular Cer and ChE, are abnormal in VaD and may help discriminate them from healthy controls. Understanding the basis of these differences may provide insights into the pathobiology of VaD.

Keywords: Lipids; Plasma biomarkers; Small vessel disease; Vascular dementia.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Standard mean difference of lipid classes. (* p < 0.05, ** p < 0.01, *** p < 0.001 **** p < 0.0001, adjusted for age, sex, diabetes, hypertension, current smoking and BMI).
Fig. 2
Fig. 2
ROC of ChE, Cer and group lipids by GLMnet and Random Forest.
See this image and copyright information in PMC

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