Mediating Role of Plasma Biomarkers Associated with Metabolic Syndrome in Cognitive Decline Among Older Adults

Purpose: Metabolic syndrome (MetS), characterized by central obesity, hypertension, hyperglycemia, and dyslipidemia, increases the risk of cardiovascular disease, type 2 diabetes, and cognitive decline in older adults. As the global population continues to age, elucidating the metabolic mechanisms linking MetS to cognitive decline is crucial. Patients and methods: We conducted a cross-sectional study to profile plasma metabolites of 42 MetS patients and 42 healthy controls (median age 69.0 and 68.5 years, respectively) using nuclear magnetic resonance (NMR) prior to mediation analysis. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and Digit Span Tests (Forward and Reverse). Results: Metabolomic analysis (PLS-DA: Q 2 = 0.41, R2 = 0.50, accuracy 78.3%) identified 13 differentially abundant metabolites, including amino acids (isoleucine, alanine, serine), fatty acid chains, lactate, glycoprotein acetylation (GlycA), acetone, and creatine. Mediation analysis showed that fatty acid chains, GlycA, acetone, lactate, and isoleucine exhibited significant competitive mediation effects between MetS and delayed recall function. Furthermore, lactate levels fully mediated the effects between MetS and attention. Conclusion: Metabolite biomarkers associated with cognitive decline in older adults with MetS were identified, with lactate, isoleucine, GlycA, acetone, and fatty acid being associated with better delayed recall performance, whereas elevated lactate levels were associated with poorer attention. Longitudinal and interventional studies are needed to confirm these pathways and clarify their implications for cognitive health in this population. The infographic presents a study on metabolic syndrome in 84 older adults in Malaysia. The methods section shows two groups: Metabolic Syndrome group with 42 participants and Control group with 42 participants. Cognitive testing and plasma metabolomics based on Nuclear Magnetic Resonance are conducted, followed by mediation analysis. The results section includes a graph labeled ’Metabolomics results’ and identifies 13 differentially abundant metabolites. A diagram illustrates the metabolic pathways, highlighting changes in glucose, lactate and other metabolites. Eight metabolites are shown to mediate the association between metabolic syndrome and cognitive function. The conclusion states that metabolic syndrome shifts glucose metabolism toward anaerobic glycolysis, increasing lactate and reducing serine and creatine synthesis. Lactate impairs attention but supports delayed recall, while isoleucine, unsaturated fatty acids and acetone may enhance delayed recall.Infographic on metabolic syndrome study in older adults, showing methods, results and conclusions.