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The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment

BACKGROUND: Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality. While lower tryptophan or a higher ratio of kynurenine/tryptophan (K/T) in peripheral bloo...

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Autores principales: Gold, Allison B, Herrmann, Nathan, Swardfager, Walter, Black, Sandra E, Aviv, Richard I, Tennen, Gayla, Kiss, Alexander, Lanctôt, Krista L
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055827/
https://www.ncbi.nlm.nih.gov/pubmed/21324164
http://dx.doi.org/10.1186/1742-2094-8-17
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author Gold, Allison B
Herrmann, Nathan
Swardfager, Walter
Black, Sandra E
Aviv, Richard I
Tennen, Gayla
Kiss, Alexander
Lanctôt, Krista L
author_facet Gold, Allison B
Herrmann, Nathan
Swardfager, Walter
Black, Sandra E
Aviv, Richard I
Tennen, Gayla
Kiss, Alexander
Lanctôt, Krista L
author_sort Gold, Allison B
collection PubMed
description BACKGROUND: Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality. While lower tryptophan or a higher ratio of kynurenine/tryptophan (K/T) in peripheral blood have been associated with dementia and the severity of cognitive symptoms in Alzheimer's disease, the association between K/T ratios and post-stroke cognitive impairment (PSCI) has not been investigated. METHODS: Patients were recruited from the acute stroke unit of a general hospital within 1 month post-stroke. Assessments included the Standardized Mini-Mental State Examination (sMMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Tryptophan and kynurenine concentrations were determined by high-performance liquid chromatography. RESULTS: A total of 41 patients with ischemic stroke ([mean ± SD] age 72.3 ± 12.2 years, 53.7% male, sMMSE 25.6 ± 4.1, NIHSS 7.27 ± 5.55) were recruited. Higher K/T ratios were associated with lower post-stroke global cognition (i.e. sMMSE scores; β = -.327, P = .037). A backward stepwise elimination linear regression (F(1,40)=6.15, P=.005, adjusted R(2)=.205) showed that the highest K/T ratio tertile (β = -.412, P = .006) predicted lower sMMSE scores, controlling for age (β = -.253, p = .081), with NIHSS (β = -.027, P = 0.859), and lesion volume (β = -.066, P = 0.659) removed from the model. In receiver operating characteristic analysis, a K/T ratio of 78.3 μmol/mmol (top tertile) predicted significant cognitive impairment (sMMSE score ≤ 24) with 67% sensitivity and 86% specificity (area under the curve = 0.730, p = .022). CONCLUSIONS: These data suggest an inflammatory response characterized by IDO activation may be relevant to the development of PSCI. Since the neuroactivity of kynurenine metabolites may be amenable to pharmacotherapeutic intervention, the K/T ratio may be a clinically important biomarker.
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spelling pubmed-30558272011-03-12 The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment Gold, Allison B Herrmann, Nathan Swardfager, Walter Black, Sandra E Aviv, Richard I Tennen, Gayla Kiss, Alexander Lanctôt, Krista L J Neuroinflammation Research BACKGROUND: Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality. While lower tryptophan or a higher ratio of kynurenine/tryptophan (K/T) in peripheral blood have been associated with dementia and the severity of cognitive symptoms in Alzheimer's disease, the association between K/T ratios and post-stroke cognitive impairment (PSCI) has not been investigated. METHODS: Patients were recruited from the acute stroke unit of a general hospital within 1 month post-stroke. Assessments included the Standardized Mini-Mental State Examination (sMMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Tryptophan and kynurenine concentrations were determined by high-performance liquid chromatography. RESULTS: A total of 41 patients with ischemic stroke ([mean ± SD] age 72.3 ± 12.2 years, 53.7% male, sMMSE 25.6 ± 4.1, NIHSS 7.27 ± 5.55) were recruited. Higher K/T ratios were associated with lower post-stroke global cognition (i.e. sMMSE scores; β = -.327, P = .037). A backward stepwise elimination linear regression (F(1,40)=6.15, P=.005, adjusted R(2)=.205) showed that the highest K/T ratio tertile (β = -.412, P = .006) predicted lower sMMSE scores, controlling for age (β = -.253, p = .081), with NIHSS (β = -.027, P = 0.859), and lesion volume (β = -.066, P = 0.659) removed from the model. In receiver operating characteristic analysis, a K/T ratio of 78.3 μmol/mmol (top tertile) predicted significant cognitive impairment (sMMSE score ≤ 24) with 67% sensitivity and 86% specificity (area under the curve = 0.730, p = .022). CONCLUSIONS: These data suggest an inflammatory response characterized by IDO activation may be relevant to the development of PSCI. Since the neuroactivity of kynurenine metabolites may be amenable to pharmacotherapeutic intervention, the K/T ratio may be a clinically important biomarker. BioMed Central 2011-02-16 /pmc/articles/PMC3055827/ /pubmed/21324164 http://dx.doi.org/10.1186/1742-2094-8-17 Text en Copyright ©2011 Gold et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Gold, Allison B
Herrmann, Nathan
Swardfager, Walter
Black, Sandra E
Aviv, Richard I
Tennen, Gayla
Kiss, Alexander
Lanctôt, Krista L
The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
title The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
title_full The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
title_fullStr The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
title_full_unstemmed The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
title_short The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
title_sort relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055827/
https://www.ncbi.nlm.nih.gov/pubmed/21324164
http://dx.doi.org/10.1186/1742-2094-8-17
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