The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study
•Tryptophan and kynurenines are related to inflammation and may be neuroactive.•Experimental studies indicates a role for the rate limiting enzyme IDO in cognition.•We assessed potential associations between kynurenines and cognition in 2174 older adults.•Lower cognitive performance is seen with hig...
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| Vydané v: | Brain, behavior, and immunity Ročník 75; s. 155 - 162 |
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| Hlavní autori: | , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Netherlands
Elsevier Inc
01.01.2019
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| ISSN: | 0889-1591, 1090-2139, 1090-2139 |
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| Abstract | •Tryptophan and kynurenines are related to inflammation and may be neuroactive.•Experimental studies indicates a role for the rate limiting enzyme IDO in cognition.•We assessed potential associations between kynurenines and cognition in 2174 older adults.•Lower cognitive performance is seen with higher kynurenine-to-tryptophan ratio and neopterin.•Our study supports that kynurenines may play a role in human cognition.
Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.
This cross-sectional study included 2174 participants aged 70–72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner’s regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5′phosphate, sex and smoking were considered as potential confounders.
Higher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β −0.08, p = 0.001) and COWAT (β −0.08, p = 0.001), but not with DST (β −0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β −0.07; p = 0.001; COWAT: β −0.06, p = 0.010; DST: β −0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition.
Higher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language. |
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| AbstractList | •Tryptophan and kynurenines are related to inflammation and may be neuroactive.•Experimental studies indicates a role for the rate limiting enzyme IDO in cognition.•We assessed potential associations between kynurenines and cognition in 2174 older adults.•Lower cognitive performance is seen with higher kynurenine-to-tryptophan ratio and neopterin.•Our study supports that kynurenines may play a role in human cognition.
Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.
This cross-sectional study included 2174 participants aged 70–72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner’s regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5′phosphate, sex and smoking were considered as potential confounders.
Higher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β −0.08, p = 0.001) and COWAT (β −0.08, p = 0.001), but not with DST (β −0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β −0.07; p = 0.001; COWAT: β −0.06, p = 0.010; DST: β −0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition.
Higher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language. Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults. This cross-sectional study included 2174 participants aged 70-72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner's regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5'phosphate, sex and smoking were considered as potential confounders. Higher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β -0.08, p = 0.001) and COWAT (β -0.08, p = 0.001), but not with DST (β -0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β -0.07; p = 0.001; COWAT: β -0.06, p = 0.010; DST: β -0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition. Higher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language. Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.INTRODUCTIONTryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.This cross-sectional study included 2174 participants aged 70-72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner's regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5'phosphate, sex and smoking were considered as potential confounders.METHODSThis cross-sectional study included 2174 participants aged 70-72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner's regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5'phosphate, sex and smoking were considered as potential confounders.Higher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β -0.08, p = 0.001) and COWAT (β -0.08, p = 0.001), but not with DST (β -0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β -0.07; p = 0.001; COWAT: β -0.06, p = 0.010; DST: β -0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition.RESULTSHigher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β -0.08, p = 0.001) and COWAT (β -0.08, p = 0.001), but not with DST (β -0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β -0.07; p = 0.001; COWAT: β -0.06, p = 0.010; DST: β -0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition.Higher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language.CONCLUSIONHigher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language. |
| Author | Midttun, Øivind Aarsland, Dag Nordrehaug, Jan Erik Smith, A. David Solvang, Stein-Erik Hafstad Giil, Lasse Melvaer Vedeler, Christian A. Nygård, Ottar McCann, Adrian Refsum, Helga Ueland, Per Magne Tell, Grethe S. Meyer, Klaus |
| Author_xml | – sequence: 1 givenname: Stein-Erik Hafstad orcidid: 0000-0003-3520-7530 surname: Solvang fullname: Solvang, Stein-Erik Hafstad email: steinerik.solvang@gmail.com organization: Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway – sequence: 2 givenname: Jan Erik surname: Nordrehaug fullname: Nordrehaug, Jan Erik organization: Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway – sequence: 3 givenname: Grethe S. surname: Tell fullname: Tell, Grethe S. organization: Department of Global Public Health and Primary Care, University of Bergen, Norway – sequence: 4 givenname: Ottar surname: Nygård fullname: Nygård, Ottar organization: Institute of Clinical Science, University of Bergen, Norway – sequence: 5 givenname: Adrian surname: McCann fullname: McCann, Adrian organization: BevitalA/S, Bergen, Norway – sequence: 6 givenname: Per Magne surname: Ueland fullname: Ueland, Per Magne organization: BevitalA/S, Bergen, Norway – sequence: 7 givenname: Øivind surname: Midttun fullname: Midttun, Øivind organization: BevitalA/S, Bergen, Norway – sequence: 8 givenname: Klaus surname: Meyer fullname: Meyer, Klaus organization: BevitalA/S, Bergen, Norway – sequence: 9 givenname: Christian A. surname: Vedeler fullname: Vedeler, Christian A. organization: Department of Clinical Medicine, University of Bergen, Norway – sequence: 10 givenname: Dag surname: Aarsland fullname: Aarsland, Dag organization: Department of Old Age Psychiatry, King’s College University, London, UK – sequence: 11 givenname: Helga surname: Refsum fullname: Refsum, Helga organization: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway – sequence: 12 givenname: A. David surname: Smith fullname: Smith, A. David organization: Department of Pharmacology, University of Oxford, UK – sequence: 13 givenname: Lasse Melvaer surname: Giil fullname: Giil, Lasse Melvaer organization: Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway |
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| Copyright | 2018 Elsevier Inc. Copyright © 2018 Elsevier Inc. All rights reserved. |
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| Keywords | Hordaland Health Study Controlled Oral Word Association Test Tryptophan metabolism Kendrick Object Learning Test Inflammation Cognition Kynurenines |
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| Snippet | •Tryptophan and kynurenines are related to inflammation and may be neuroactive.•Experimental studies indicates a role for the rate limiting enzyme IDO in... Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the... |
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| Title | The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study |
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