Untargeted Metabolomics Shows Alterations in Homocysteine, Lipids and Fatty Acids predicting Memory Decline in Healthy Middle-Aged Individuals

Ihab Hajjar, Qingpo Cai, Tianwei Yu, Dean P. Jones
2020 · doi:10.1101/2020.02.23.949537
preprint OA: closed
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Abstract

INTRODUCTION Some aspects of memory start declining in the fifth decade which may be related to systemic metabolic changes. These changes have not been fully identified. This is the first Metabolome-Wide Association Study of the human plasma for the longitudinal change in memory in healthy adults. METHODS Ultra-high resolution mass spectrometry with liquid chromatography was performed on 207 University employees’ plasma. RESULTS From 10,201 measured metabolic features, 558 differed between those experiencing change vs no change in memory (False Discovery Rate, FDR< 0.2). Differentially abundant metabolites were observed in lipid and fatty acid metabolism pathways: glycerophospholipid (p=0.0003), fatty acid (p=0.0003) and linoleate (p=0.0003) pathways. Within these pathways, higher homocysteine (OR for memory decline=1.09, FDR=0.19) and lower arachidonic acid (OR=0.97, FDR=0.19), sterol (OR=0.92, FDR=0.02), acetylcholine (OR=0.78, FDR=0.19), carnitine (OR=0.75, FDR=0.19) and linoleic acid (OR=0.74, FDR=0.19) were associated memory decline. DISCUSSION Altered systemic lipid and fatty acid are linked with early memory decline in middle-aged individuals.

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