Cargando…
Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia
INTRODUCTION: Circulating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia. OBJECTIVE: The objective of this study was to assess assoc...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769202/ https://www.ncbi.nlm.nih.gov/pubmed/31632053 http://dx.doi.org/10.1177/1178646919877883 |
_version_ | 1783455197536714752 |
---|---|
author | Solvang, Stein-Erik Hafstad Nordrehaug, Jan Erik Aarsland, Dag Lange, Johannes Ueland, Per Magne McCann, Adrian Midttun, Øivind Tell, Grethe S Giil, Lasse Melvaer |
author_facet | Solvang, Stein-Erik Hafstad Nordrehaug, Jan Erik Aarsland, Dag Lange, Johannes Ueland, Per Magne McCann, Adrian Midttun, Øivind Tell, Grethe S Giil, Lasse Melvaer |
author_sort | Solvang, Stein-Erik Hafstad |
collection | PubMed |
description | INTRODUCTION: Circulating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia. OBJECTIVE: The objective of this study was to assess associations between circulating kynurenines, cognitive prognosis, and neuropsychiatric symptoms. METHODS: We measured baseline serum Trp, neopterin, pyridoxal 5′-phosphate (PLP), and 9 kynurenines in 155 patients with mild dementia (90 with Alzheimer’s disease, 65 with Lewy body dementia). The ratios between kynurenine and Trp and kynurenic acid (KA) to kynurenine (KKR) were calculated. The Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered at baseline and annually over 5 years. Associations between baseline metabolite concentrations with MMSE and the NPI total score were assessed using a generalized structural equation model (mixed-effects multiprocess model), adjusted for age, sex, current smoking, glomerular filtration rate, and PLP. Post hoc associations between KKRs and individual NPI items were assessed using logistic mixed-effects models. False discovery rate (0.05)–adjusted P values (Q values) are reported. RESULTS: Kynurenine had a nonlinear quadratic relationship with the intercept of the MMSE scores over 5 years (Q < 0.05), but not with the slope of MMSE decline. Kynurenine was associated with a higher NPI total score over time (Q < 0.001). Post hoc, both KKR and KA were associated with more hallucinations (Q < 0.05). CONCLUSIONS: Kynurenine has a complex relationship with cognition, where both low and high levels were associated with poor cognitive performance. A higher KKR indicated risk for neuropsychiatric symptoms, especially hallucinations. |
format | Online Article Text |
id | pubmed-6769202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-67692022019-10-18 Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia Solvang, Stein-Erik Hafstad Nordrehaug, Jan Erik Aarsland, Dag Lange, Johannes Ueland, Per Magne McCann, Adrian Midttun, Øivind Tell, Grethe S Giil, Lasse Melvaer Int J Tryptophan Res Original Research INTRODUCTION: Circulating tryptophan (Trp) and its downstream metabolites, the kynurenines, are potentially neuroactive. Consequently, they could be associated with neuropsychiatric symptoms and cognitive prognosis in patients with dementia. OBJECTIVE: The objective of this study was to assess associations between circulating kynurenines, cognitive prognosis, and neuropsychiatric symptoms. METHODS: We measured baseline serum Trp, neopterin, pyridoxal 5′-phosphate (PLP), and 9 kynurenines in 155 patients with mild dementia (90 with Alzheimer’s disease, 65 with Lewy body dementia). The ratios between kynurenine and Trp and kynurenic acid (KA) to kynurenine (KKR) were calculated. The Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered at baseline and annually over 5 years. Associations between baseline metabolite concentrations with MMSE and the NPI total score were assessed using a generalized structural equation model (mixed-effects multiprocess model), adjusted for age, sex, current smoking, glomerular filtration rate, and PLP. Post hoc associations between KKRs and individual NPI items were assessed using logistic mixed-effects models. False discovery rate (0.05)–adjusted P values (Q values) are reported. RESULTS: Kynurenine had a nonlinear quadratic relationship with the intercept of the MMSE scores over 5 years (Q < 0.05), but not with the slope of MMSE decline. Kynurenine was associated with a higher NPI total score over time (Q < 0.001). Post hoc, both KKR and KA were associated with more hallucinations (Q < 0.05). CONCLUSIONS: Kynurenine has a complex relationship with cognition, where both low and high levels were associated with poor cognitive performance. A higher KKR indicated risk for neuropsychiatric symptoms, especially hallucinations. SAGE Publications 2019-09-29 /pmc/articles/PMC6769202/ /pubmed/31632053 http://dx.doi.org/10.1177/1178646919877883 Text en © The Author(s) 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Solvang, Stein-Erik Hafstad Nordrehaug, Jan Erik Aarsland, Dag Lange, Johannes Ueland, Per Magne McCann, Adrian Midttun, Øivind Tell, Grethe S Giil, Lasse Melvaer Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia |
title | Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in
Patients with Mild Dementia |
title_full | Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in
Patients with Mild Dementia |
title_fullStr | Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in
Patients with Mild Dementia |
title_full_unstemmed | Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in
Patients with Mild Dementia |
title_short | Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in
Patients with Mild Dementia |
title_sort | kynurenines, neuropsychiatric symptoms, and cognitive prognosis in
patients with mild dementia |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769202/ https://www.ncbi.nlm.nih.gov/pubmed/31632053 http://dx.doi.org/10.1177/1178646919877883 |
work_keys_str_mv | AT solvangsteinerikhafstad kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT nordrehaugjanerik kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT aarslanddag kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT langejohannes kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT uelandpermagne kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT mccannadrian kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT midttunøivind kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT tellgrethes kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia AT giillassemelvaer kynureninesneuropsychiatricsymptomsandcognitiveprognosisinpatientswithmilddementia |