Observational studyThe Journal of clinical investigation2023
Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients.
Observational study in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Inflammation and delirium in critically Ill patients: a review.Frontiers in aging neuroscience · 2026Pooled it
- Dissecting the genetic and proteomic risk factors for delirium.Nature aging · 2026Pooled it
- Metabolome Profiling of Yokukansan in Preventing Postoperative Delirium in Elderly Cancer Patients: A Reverse Translational Study.Psychiatry and clinical neurosciences · 2025Trial
- Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review).International journal of molecular medicine · 2026Review
- CSF neurofilament light chain concentration in patients with delirium following hip fracture: a multicenter prospective study.BMC geriatrics · 2026Observational
- Biomarkers of Alzheimer's disease pathophysiology and delirium.EBioMedicine · 2026Article
- Blood-Brain Barrier Permeability in Cases of Post-operative Delirium Is Associated with Central Nervous System Phosphatidylcholine Imbalances.Molecular neurobiology · 2026Article
- Brain fatigue in Graves' disease: symptoms and presentation of a possible mechanism at the cellular level.European thyroid journal · 2026Review
- Evaluation of Cranberry as a Novel Therapeutic Strategy for Intracerebroventricular (ICV) Quinolinic Acid-induced Cognitive Impairment in Rats.Combinatorial chemistry & high throughput screening · 2026Article
- Delirium prevalence and incidence in acutely admitted older patients: an observational cohort study.BMC geriatrics · 2025Observational
- Article
- Causal links between mitochondrial genes, cerebrospinal fluid metabolites, and delirium: a mendelian randomization study.Arquivos de neuro-psiquiatria · 2025Article
- Article
- Mechanisms of perioperative neuronal injury and the search for therapies.British journal of anaesthesia · 2025Article
- Quinolinic acid potentially links kidney injury to brain toxicity.JCI insight · 2025Article
- Increased cell-free DNA in CSF and serum of hip fracture patients with delirium.Brain communications · 2025Article
- Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium.Communications medicine · 2024Article
- Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia: Recent Progress on the Mechanisms and Interventional Strategies.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Impaired glucose utilization in the brain of patients with delirium following hip fracture.Brain : a journal of neurology · 2024Article
- Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury.Brain communications · 2024Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
BACKGROUNDThe 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 mechanisms underlying delirium, particularly in relation to the KP, remain elusive.METHODSWe undertook a multicenter 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 1-year mortality.RESULTSIn 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 and also found 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 1-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.CONCLUSIONOur 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.FUNDINGNorwegian Health Association and South-Eastern Norway Regional Health Authorities.
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