Watne, Leiv Otto;
Pollmann, Christian Thomas;
Neerland, Bjorn Erik;
Quist-Paulsen, Else;
Halaas, Nathalie Bodd;
Idland, Ane-Victoria;
Hassel, Bjørnar;
... Giil, Lasse M; + view all
(2022)
Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip fracture patients.
Journal of Clinical Investigation
, Article e163472. 10.1172/JCI163472.
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Abstract
BACKGROUND: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive. METHODS: We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality. RESULTS: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p<0.001) to be increased, as well as increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL, β 0.43, p<0.001) and was a strong predictor of one-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, p<0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons. CONCLUSION: Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP, and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP. FUNDING: Norwegian Health Association and the South-Eastern Norway Regional Health Authorities.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip fracture patients |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI163472 |
| Publisher version: | https://doi.org/10.1172/JCI163472 |
| Language: | English |
| Additional information: | Copyright © 2022, Watne et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Dementia, Inflammation, Metabolism, Neurological disorders, Psychiatric diseases |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10160931 |
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