Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study
•Higher degree of systemic inflammation was associated with cognitive dysfunction.•Higher levels of neopterin & quinolinic acid were associated with poorer cognition.•Higher levels of vitamin B6 were associated with better cognitive results.•Inflammation in the acute phase had the largest impact...
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| Veröffentlicht in: | Brain, behavior, and immunity behavior, and immunity, 2024-05, Vol.118, p.167-177 |
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| creator | Sandvig, Heidi Vihovde Aam, Stina Alme, Katinka N. Lydersen, Stian Magne Ueland, Per Ulvik, Arve Wethal, Torgeir Saltvedt, Ingvild Knapskog, Anne-Brita |
| description | •Higher degree of systemic inflammation was associated with cognitive dysfunction.•Higher levels of neopterin & quinolinic acid were associated with poorer cognition.•Higher levels of vitamin B6 were associated with better cognitive results.•Inflammation in the acute phase had the largest impact on cognitive outcomes.•We have identified promising biomarkers of post-stroke cognitive impairment.
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.
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.
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 |
| doi_str_mv | 10.1016/j.bbi.2024.02.030 |
| format | Article |
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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.
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.
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).
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.</description><identifier>ISSN: 0889-1591</identifier><identifier>EISSN: 1090-2139</identifier><identifier>DOI: 10.1016/j.bbi.2024.02.030</identifier><identifier>PMID: 38428649</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Aged ; B6 vitamin ; Biomarker ; Biomarkers ; Cognitive Dysfunction - complications ; Cohort Studies ; Female ; Humans ; Inflammation - complications ; Ischemic stroke ; Kynurenine - metabolism ; Kynurenine pathway ; Male ; Neopterin ; Plasma ; Post-stroke cognitive impairment ; Prospective Studies ; Pyridoxal Phosphate ; Quinolinic acid ; Stroke - complications ; Vitamin B 6 - metabolism</subject><ispartof>Brain, behavior, and immunity, 2024-05, Vol.118, p.167-177</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c348t-87938a097fcd6d649ab5e6d576c9dd71006f6b5f8e2502625de1e476c492ac913</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0889159124002745$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38428649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sandvig, Heidi Vihovde</creatorcontrib><creatorcontrib>Aam, Stina</creatorcontrib><creatorcontrib>Alme, Katinka N.</creatorcontrib><creatorcontrib>Lydersen, Stian</creatorcontrib><creatorcontrib>Magne Ueland, Per</creatorcontrib><creatorcontrib>Ulvik, Arve</creatorcontrib><creatorcontrib>Wethal, Torgeir</creatorcontrib><creatorcontrib>Saltvedt, Ingvild</creatorcontrib><creatorcontrib>Knapskog, Anne-Brita</creatorcontrib><title>Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study</title><title>Brain, behavior, and immunity</title><addtitle>Brain Behav Immun</addtitle><description>•Higher degree of systemic inflammation was associated with cognitive dysfunction.•Higher levels of neopterin & quinolinic acid were associated with poorer cognition.•Higher levels of vitamin B6 were associated with better cognitive results.•Inflammation in the acute phase had the largest impact on cognitive outcomes.•We have identified promising biomarkers of post-stroke cognitive impairment.
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.
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.
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).
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.</description><subject>Aged</subject><subject>B6 vitamin</subject><subject>Biomarker</subject><subject>Biomarkers</subject><subject>Cognitive Dysfunction - complications</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation - complications</subject><subject>Ischemic stroke</subject><subject>Kynurenine - metabolism</subject><subject>Kynurenine pathway</subject><subject>Male</subject><subject>Neopterin</subject><subject>Plasma</subject><subject>Post-stroke cognitive impairment</subject><subject>Prospective Studies</subject><subject>Pyridoxal Phosphate</subject><subject>Quinolinic acid</subject><subject>Stroke - complications</subject><subject>Vitamin B 6 - metabolism</subject><issn>0889-1591</issn><issn>1090-2139</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EotPCA7BBXrJogu0kHhtW7aj8SFW7YFhbjn1DPU3sYDsD8xI8My5TWLK6i_OdI517EHpFSU0J5W93dd-7mhHW1oTVpCFP0IoSSSpGG_kUrYgQsqKdpCfoNKUdIaRrqHiOThrRMsFbuUK_biDMGaLz5_j-4JcI3nnAE2Tdh9FlSOdYe4udt_ATEo4w6gwW54D3LuvJeXzJsY6AdUrBuD_iD5fv8BxSrlKO4R6wCd-8y24P2E2zdnECn9_h7R3gmxCrze3Fly1OebGHF-jZoMcELx_vGfr64Wq7-VRd3378vLm4rkzTilyJtWyEJnI9GMttKaL7Drjt1txIa9eUED7wvhsEsI4wzjoLFNqitpJpI2lzht4cc-cYvi-QsppcMjCO2kNYkmKyaRkXxVxQekRNDClFGNQc3aTjQVGiHmZQO1VmUA8zKMJUmaF4Xj_GL_0E9p_j798L8P4IQCm5dxBVMg68AesimKxscP-J_w0V75mm</recordid><startdate>202405</startdate><enddate>202405</enddate><creator>Sandvig, Heidi Vihovde</creator><creator>Aam, Stina</creator><creator>Alme, Katinka N.</creator><creator>Lydersen, Stian</creator><creator>Magne Ueland, Per</creator><creator>Ulvik, Arve</creator><creator>Wethal, Torgeir</creator><creator>Saltvedt, Ingvild</creator><creator>Knapskog, Anne-Brita</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202405</creationdate><title>Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study</title><author>Sandvig, Heidi Vihovde ; Aam, Stina ; Alme, Katinka N. ; Lydersen, Stian ; Magne Ueland, Per ; Ulvik, Arve ; Wethal, Torgeir ; Saltvedt, Ingvild ; Knapskog, Anne-Brita</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-87938a097fcd6d649ab5e6d576c9dd71006f6b5f8e2502625de1e476c492ac913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>B6 vitamin</topic><topic>Biomarker</topic><topic>Biomarkers</topic><topic>Cognitive Dysfunction - complications</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation - complications</topic><topic>Ischemic stroke</topic><topic>Kynurenine - metabolism</topic><topic>Kynurenine pathway</topic><topic>Male</topic><topic>Neopterin</topic><topic>Plasma</topic><topic>Post-stroke cognitive impairment</topic><topic>Prospective Studies</topic><topic>Pyridoxal Phosphate</topic><topic>Quinolinic acid</topic><topic>Stroke - complications</topic><topic>Vitamin B 6 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sandvig, Heidi Vihovde</creatorcontrib><creatorcontrib>Aam, Stina</creatorcontrib><creatorcontrib>Alme, Katinka N.</creatorcontrib><creatorcontrib>Lydersen, Stian</creatorcontrib><creatorcontrib>Magne Ueland, Per</creatorcontrib><creatorcontrib>Ulvik, Arve</creatorcontrib><creatorcontrib>Wethal, Torgeir</creatorcontrib><creatorcontrib>Saltvedt, Ingvild</creatorcontrib><creatorcontrib>Knapskog, Anne-Brita</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Brain, behavior, and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sandvig, Heidi Vihovde</au><au>Aam, Stina</au><au>Alme, Katinka N.</au><au>Lydersen, Stian</au><au>Magne Ueland, Per</au><au>Ulvik, Arve</au><au>Wethal, Torgeir</au><au>Saltvedt, Ingvild</au><au>Knapskog, Anne-Brita</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study</atitle><jtitle>Brain, behavior, and immunity</jtitle><addtitle>Brain Behav Immun</addtitle><date>2024-05</date><risdate>2024</risdate><volume>118</volume><spage>167</spage><epage>177</epage><pages>167-177</pages><issn>0889-1591</issn><eissn>1090-2139</eissn><abstract>•Higher degree of systemic inflammation was associated with cognitive dysfunction.•Higher levels of neopterin & quinolinic acid were associated with poorer cognition.•Higher levels of vitamin B6 were associated with better cognitive results.•Inflammation in the acute phase had the largest impact on cognitive outcomes.•We have identified promising biomarkers of post-stroke cognitive impairment.
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.
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.
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).
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.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>38428649</pmid><doi>10.1016/j.bbi.2024.02.030</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged B6 vitamin Biomarker Biomarkers Cognitive Dysfunction - complications Cohort Studies Female Humans Inflammation - complications Ischemic stroke Kynurenine - metabolism Kynurenine pathway Male Neopterin Plasma Post-stroke cognitive impairment Prospective Studies Pyridoxal Phosphate Quinolinic acid Stroke - complications Vitamin B 6 - metabolism |
| title | Neopterin, kynurenine metabolites, and indexes related to vitamin B6 are associated with post-stroke cognitive impairment: The Nor-COAST study |
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