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

Abstract

INTRODUCTIONSome 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. METHODSUltra-high resolution mass spectrometry with liquid chromatography was performed on 207 University employees plasma. RESULTSFrom 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. DISCUSSIONAltered systemic lipid and fatty acid are linked with early memory decline in middle-aged individuals.