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An elaborative NMR based plasma metabolomics study revealed metabolic derangements in patients with mild cognitive impairment: a study on north Indian population

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Abstract

Mild cognitive impairment (MCI) is transition phase between cognitive decline and dementia. The current study aims to investigate altered metabolic pattern in plasma of MCI for potential biomarkers. MCI (N = 50) and healthy controls (HC, N = 50) age group 55–75 years were screened based on Mini Mental State Examination Test (MMSE) and diffusion tensor imaging (DTI imaging). The MMSE score of MCI was significantly lower (25.74 ± 1.83) compared to healthy control subjects (29 ± 1). The MCI patients exhibit significant changes in white matter integrity in the right frontal lobe, right temporal lobe, left frontal lobe, forcep major, fornix, corpus callosum. Further, the plasma samples of twenty seven MCI patients (N = 27) and twenty HC subjects (N = 20; having no significant differences in any demographics) were analyzed using 1H NMR based metabolomics approach. Consistent with many previous reports, the levels of several plasma metabolites were found to be elevated in MCI patients compared to healthy controls. Further univariate and multivariate ROC curve analyses provided three plasma metabolites as a diagnostic panel of biomarker for MCI; which are lysine, glycine, and glutamine. Overall, the results of this study will help to improve the diagnostic and prognostic strategies of MCI in addition to improving our understanding about disease pathogenesis. We believe that the over-nutritional metabolic phenotype of MCI needs to be targeted for developing future dietary interventions so that the progression of MCI can be limited.

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Metabolic derangements associated with Mild Cognitive Impairment

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Data availability

All relevant data are within the manuscript and its Supporting Information files. The raw NMR spectral data will be provided on request.

Abbreviations

AD:

Alzheimer’s disease.

HC:

Healthy control.

NMR:

Nuclear Magnetic Resonance.

MCI:

Mild Cognitive Impairment.

ROC:

Receiver operating characteristic curve.

VIP:

Variable importance for the projection.

APOE:

apolipoprotein E.

CSF:

Cerebrospinal fluid.

AUROC:

Area under ROC curve.

ESM:

Electronic Supplementary Material.

CI:

Confidence interval.

TCA:

Tricarboxylic acid.

PUFAs:

Polyunsaturated fatty acids.

NAG:

N-acetyl-glycoproteins.

FA:

Fractional Anisotropy.

MMSE:

Mini-Mental State Examination.

DTI:

Diffusion tensor imaging.

GPC:

Glycerophosphocholine.

LDL:

Low-density lipoproteins.

VLDL:

Very Low-density lipoproteins.

CPMG:

Carr–Purcell–Meiboom–Gill.

PCA:

Principal component analysis.

PLS-DA:

Projection to least-squares discriminant analysis.

OPLS-DA:

PLS-DA with Orthogonal Signal Correction(OSC).

PTR:

Phenylalanine to tyrosine ratio.

HTR:

Histidine to tyrosine ratio.

EQR:

Glutamate to Glutamine ratio

BTR:

Branched-chain amino acid to Tyrosine ratio.

LPR:

Lactate to Pyruvate ratio.

CT:

Computerized tomography.

GPC:

Glycerophosphocholine.

OSC:

Orthogonal Signal Correction.

PS-1/PS-2:

Presenilin-1/Presenilin-2.

ADC:

Apparent diffusion coefficient.

1D/2D:

One/two dimensional.

TCA:

Tricarboxylic acid.

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Acknowledgments

Authors would also like to acknowledge the Department of Medical Education, Govt. of Uttar Pradesh for supporting the High Field NMR Facility at Centre of Biomedical Research, Lucknow, India. SS acknowledges the receipt of PDF Fellowship from Cognitive Science Research Initiative Program of DST, India and SKS acknowledges RA fellowship from The Indian Council of Medical Research (ICMR), New Delhi, India. AK acknowledges the financial assistance from Department of Science and Technology, Govt of India support scheme DST/CSRI/PDF-63/2018 under Cognitive Science Research Initiative program DK acknowledges the Department of Science and Technology for financial assistance under SERB EMR Scheme (Ref. No.: EMR/2016/001756). UK acknowledges receipt of the SRF fellowship [ICMR sanction no.3/1/3/JRF-2014/HRD-100 (32508)]. Other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Centre of Biomedical Research (CBMR), SGPGIMS Campus, Raibareli Road, Lucknow, Uttar Pradesh, 226014, India

    Umesh Kumar, Payal Arya, Sandeep Kumar Singh & Dinesh Kumar

  2. Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    Abhai Kumar & Rameshwar Nath Chaurasia

  3. Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    Smita Singh & Anup Singh

  4. Indian Scientific Education and Technology Foundation, Lucknow, 226002, India

    Sandeep Kumar Singh

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Smita Singh (SS), Rameshwar Nath Chaurasia (RNC) and Anup Singh (AS) helped in the clinical screening of patients, imaging analysis and clinical data collection. Umesh Kumar (UK), Sandeep Kumar Singh (SKS) and Payal Arya (PA) processed plasma samples, prepared the NMR samples and recorded the NMR spectra. Dinesh Kumar (DK) and Abhai Kumar (AK) analyzed Metabolomics data, prepared the Figures and drafted the manuscript.

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Kumar, U., Kumar, A., Singh, S. et al. An elaborative NMR based plasma metabolomics study revealed metabolic derangements in patients with mild cognitive impairment: a study on north Indian population. Metab Brain Dis 36, 957–968 (2021). https://doi.org/10.1007/s11011-021-00700-z

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