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Cerebrospinal fluid...
Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip fracture patients.
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Watne, Leiv Otto (author)
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Pollmann, Christian Thomas (author)
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Neerland, Bjorn Erik (author)
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Quist-Paulsen, Else (author)
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Halaas, Nathalie Bodd (author)
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Idland, Ane-Victoria (author)
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Hassel, Bjørnar (author)
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Henjum, Kristi (author)
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Knapskog, Anne-Brita (author)
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Frihagen, Frede (author)
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Raeder, Johan (author)
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Godø, Aasmund (author)
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Ueland, Per Magne (author)
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McCann, Adrian (author)
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Figved, Wender (author)
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Selbæk, Geir (author)
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Fang, Evandro Fei (author)
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Myrstad, Marius (author)
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Giil, Lasse M (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: The Journal of clinical investigation. - 1558-8238. ; 133:2
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https://doi.org/10.1...
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Abstract
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- 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.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.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.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.Norwegian Health Association and the South-Eastern Norway Regional Health Authorities.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Watne, Leiv Otto
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Pollmann, Christ ...
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Neerland, Bjorn ...
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Quist-Paulsen, E ...
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Halaas, Nathalie ...
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Idland, Ane-Vict ...
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show more...
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Hassel, Bjørnar
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Henjum, Kristi
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Knapskog, Anne-B ...
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Frihagen, Frede
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Raeder, Johan
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Godø, Aasmund
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Ueland, Per Magn ...
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McCann, Adrian
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Figved, Wender
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Selbæk, Geir
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Zetterberg, Henr ...
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Fang, Evandro Fe ...
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Myrstad, Marius
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Giil, Lasse M
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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The Journal of c ...
- By the university
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University of Gothenburg