Rimjhim Trivedi (Centre of Biomedical Research, India)
LinkedIn: Rimjhim Trivedi, X: @rimjhimtrivedi1
Abstract: Cognitive decline is a major age-related neurodegenerative condition lacking minimally invasive biomarkers. Systemic metabolic changes often mirror brain bioenergetic dysfunction, offering potential indicators of disease progression. This study used quantitative 1H NMR-based serum metabolomics to identify metabolic signatures linked to cognitive decline (CD, n = 40) compared with cognitively normal controls (NCD, n = 54). High-field 800 MHz 1H NMR spectroscopy was applied, followed by multivariate (PCA, OPLS-DA, Random Forest) and univariate analyses. Receiver operating characteristic (ROC) analysis assessed diagnostic performance, while correlations with Mini-Mental State Examination (MMSE) scores evaluated clinical relevance. Thirty-three metabolites and key ratios were quantified. CD subjects showed elevated glucose, pyruvate, acetate, acetoacetate, creatine, mannose, and urea, with reduced lactate, alanine, histidine, glutamine, glutamate, and branched-chain amino acids. Ratios including glutamine-to-glucose (QGR), alanine-to-glucose (AGR), and histidine-to-tyrosine (HTR) were significantly decreased. AGR and QGR declined with disease severity, and AGR correlated positively with MMSE scores. ROC analysis demonstrated strong diagnostic performance for QGR (AUC = 0.876), AGR (AUC = 0.840), and HTR (AUC = 0.822). Pathway analysis indicated impaired glycolysis-mitochondrial coupling, reduced pyruvate dehydrogenase activity, altered amino acid metabolism, and compensatory ketone/fatty-acid utilization. These findings highlight serum metabolomics as a promising non-invasive approach for assessing cognitive decline and monitoring progression.
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