Cited by 80Dementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and TreatmentsMetabolomics and Mass Spectrometry Studies

Targeted metabolomic analysis of nitric oxide/L-arginine pathway metabolites in dementia: Association with pathology, severity, and structural brain changes

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Fleszar, Mariusz G., Wiśniewski, Jerzy, Zboch, Marzena, Diakowska, Dorota, Gamian, Andrzej, Krzystek-Korpacka, Małgorzata·2019·Scientific Reports

Abstract

L-Arginine/NO pathway is altered in Alzheimer disease (AD). Its clinical relevance and pathway status in vascular dementia (VaD) are unknown. Using targeted metabolomics (a liquid chromatography-mass spectrometry) we assessed L-arginine, L-citrulline, dimethylamine (DMA), asymmetric dimethyl arginine (ADMA) and symmetric dimethylarginine (SDMA) in AD (n = 48), mixed-type dementia (MD; n = 34), VaD (n = 40) and non-demented individuals (n = 140) and determined their clinical relevance (the association with dementia pathology, cognitive impairment, and structural brain damage). L-Arginine, ADMA, L-arginine/ADMA, and L-citrulline levels were decreased in dementia and L-arginine, L-citrulline, age and sex were its independent predictors correctly classifying 91% of cases. L-Arginine and L-arginine/ADMA were differentiating between VaD and AD with moderate accuracy. L-Arginine, L-arginine/ADMA, SDMA, and DMA reflected structural brain changes. DMA and L-citrulline were elevated in patients with strategic infarcts and SDMA, L-arginine/ADMA, and DMA were independent predictors of Hachinski ischemic score. ADMA and SDMA accumulation reflected severity of cognitive impairment. In summary, L-Arginine/NO pathway is altered in neurodegenerative and vascular dementia in association with neurodegenerative and vascular markers of brain damage and severity of cognitive impairment.

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  1. [53]American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (4th ed., text rev.) Washington; ISBN 0890420254 (2000)
  2. [55]World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 10th Revision Vol. 41, ISBN 9241544198 (1992)

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Authors
Fleszar, M. G., Wiśniewski, J., Zboch, M., Diakowska, D., Gamian, A., & Krzystek-Korpacka, M.
Affiliations
Wroclaw Medical University (PL)
Venue
Scientific Reports
Published
2019-09-24
Volume
9
Issue
1
Pages
13764-13764
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2976246130
Cited by
80
References
66
Citations by year
2026: 13 · 2025: 10 · 2024: 9 · 2023: 15 · 2022: 12 · 2021: 11 · 2020: 9 · 2019: 1
FWCI
6.56
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Uniwersytet Medyczny im. Piastów Slaskich we Wroclawiu (#ST-882)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
Alzheimer's disease, vascular dementia, L-arginine, citrulline, asymmetric dimethylarginine, symmetric dimethylarginine, dimethylamine, dementia biomarkers, cognitive impairment severity, cerebral infarction, Hachinski Ischemic Score, structural brain damage, dementia classification
MeSH terms
Arginine, Brain, Citrulline, Dementia, Female, Humans, Male, Middle Aged, Nitric Oxide, Signal Transduction, Biomarkers, Metabolomics

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