학술논문

Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study.
Document Type
Academic Journal
Author
Sandvig HV; Department of Medicine, Kristiansund Hospital, Møre og Romsdal Hospital Trust, Kristiansund, Norway; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: heidi.v.sandvig@ntnu.no.; Aam S; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.; Alme KN; Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.; Lydersen S; Department of Mental Health, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway.; Magne Ueland P; Bevital A/S, Laboratoriebygget, 5021 Bergen, Norway.; Ulvik A; Bevital A/S, Laboratoriebygget, 5021 Bergen, Norway.; Wethal T; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Stroke, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.; Saltvedt I; Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Geriatric Medicine, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.; Knapskog AB; Department of Geriatric Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway.
Source
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE
Subject
Language
English
Abstract
Background and Aims: We have previously shown that systemic inflammation was associated with post-stroke cognitive impairment (PSCI). Because neopterin, kynurenine pathway (KP) metabolites, and B6 vitamers are linked to inflammation, in our study we investigated whether those biomarkers were associated with PSCI.
Material and Methods: The Norwegian Cognitive Impairment After Stroke study is a prospective multicenter cohort study of patients with acute stroke recruited from May 2015 through March 2017. Plasma samples of 422 participants (59 % male) with ischemic stroke from the index hospital stay and 3 months post-stroke were available for analyses of neopterin, KP metabolites, and B6 vitamers using liquid chromatography-tandem mass spectrometry. Mixed linear regression analyses adjusted for age, sex, and creatinine, were used to assess whether there were associations between those biomarkers and cognitive outcomes, measured by the Montreal Cognitive Assessment scale (MoCA) at 3-, 18-, and 36-month follow-up.
Results: Participants had a mean (SD) age of 72 (12) years, with a mean (SD) National Institutes of HealthStroke Scale score of 2.7 (3.6) at Day 1. Higher baseline values of quinolinic acid, PAr (i.e., an inflammatory marker based on vitamin B6 metabolites), and HKr (i.e., a marker of functional vitamin B6 status based on selected KP metabolites) were associated with lower MoCA score at 3, 18, and 36 months post-stroke (p < 0.01). Higher baseline concentrations of neopterin and 3-hydroxykynurenine were associated with lower MoCA scores at 18 and 36 months, and higher concentrations of xanthurenic acid were associated with higher MoCA score at 36 months (p < 0.01). At 3 months post-stroke, higher concentrations of neopterin and lower values of pyridoxal 5́-phosphate were associated with lower MoCA scores at 18- and 36-month follow-up, while lower concentrations of picolinic acid were associated with a lower MoCA score at 36 months (p < 0.01).
Conclusion: Biomarkers and metabolites of systemic inflammation, including biomarkers of cellular immune activation, indexes of vitamin B6 homeostasis, and several neuroactive metabolites of the KP pathway, were associated with PSCI.
Trial Registration: ClinicalTrials.gov: NCT02650531.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)