Increased cerebrospinal fluid YKL-40 concentration in hip fracture patients with delirium.
| Title: | Increased cerebrospinal fluid YKL-40 concentration in hip fracture patients with delirium. |
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| Authors: | Berntsen T; Oslo Delirium Research Group, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway.; Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway.; Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal S-431 80, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal S-431 80, Sweden.; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris 75646, France.; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei 230001, China.; Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal S-431 80, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal S-431 80, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1E 6BT, UK.; UK Dementia Research Institute at UCL, London WC1E 6BT, UK.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Shatin, People's Republic of China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792-2420, USA.; Fæhn Brekke I; Department of Anaesthesiology, Oslo University Hospital, Oslo 0424, Norway.; Petersen Hella MN; Department of Geriatric Medicine, Stavanger University Hospital, Stavanger 4011, Norway.; Department of Clinical Medicine, University of Bergen, Bergen 5021, Norway.; Lian TT; Department of Orthopaedic Surgery, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum 1346, Norway.; Solberg LB; Division of Orthopaedic Surgery, Oslo University Hospital, Oslo 0424, Norway.; Pollmann CT; Department of Orthopaedic Surgery, Akershus University Hospital, Lørenskog 1478, Norway.; Karabeg A; Department of Orthopaedic Surgery, Akershus University Hospital, Kongsvinger 2212, Norway.; Ødegaard OT; Department of Anaesthesiology, Akershus University Hospital, Kongsvinger 2212, Norway.; Myrstad M; Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum 1346, Norway.; Sydnes K; Department of Surgery and Anaesthesia, Unit for Orthopaedic Surgery, Diakonhjemmet Hospital, Oslo 0319, Norway.; Bjørkholt Olsen R; Department of Anaesthesiology and Intensive Care, Sørlandet Hospital, Arendal 4838, Norway.; Bruun Wyller T; Oslo Delirium Research Group, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway.; Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway.; Watne LO; Oslo Delirium Research Group, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway.; Department of Geriatric Medicine, Akershus University Hospital, Lørenskog 1478, Norway.; Neerland BE; Oslo Delirium Research Group, Institute of Clinical Medicine, University of Oslo, Oslo 0318, Norway.; Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway. |
| Source: | Brain communications [Brain Commun] 2026 Feb 25; Vol. 8 (1), pp. fcag005. Date of Electronic Publication: 2026 Feb 25 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101755125 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-1297 (Electronic) Linking ISSN: 26321297 NLM ISO Abbreviation: Brain Commun Subsets: In Process |
| Imprint Name(s): | Original Publication: [Oxford] : Oxford University Press, [2019]- |
| Abstract: | The underlying mechanisms of the neuropsychiatric syndrome delirium are still unknown, but neuroinflammation is a central hypothesis. Chitinase-3-like-protein-1 (YKL-40/CHI3L1) is considered a marker of neuroinflammation when measured in cerebrospinal fluid (CSF). The aim of this study was to examine concentrations of CSF YKL-40 in patients with and without delirium, to enhance the understanding of delirium pathophysiology. A total of 545 hip fracture patients were included from two similar cohorts. CSF samples were collected in conjunction with spinal anaesthesia for hip fracture surgery. The patients were screened for delirium both pre- and postoperatively. Those with delirium were further divided into subgroups based on whether they developed it before surgery (prevalent delirium) or after surgery (incident delirium). Among patients without delirium, those who met some, but not all diagnostic criteria, were classified as having subsyndromal delirium. Prefracture cognitive function was assessed, and American Society of Anaesthesiologists physical status score was included as a marker of comorbidity. In total, 257 (47%) of the patients developed delirium. These patients were older and had a higher prevalence of dementia and severe systemic diseases. Among the patients without dementia, those with delirium had higher median concentration of CSF YKL-40 compared with those without delirium (first cohort: 175 versus 132 ng/mL, P = 0.01, second cohort: 243 versus 174 ng/mL, P < 0.001). No association was found among the patients with dementia. The results remained consistent when adjusting for age and comorbidity. No difference in median CSF YKL-40 concentration was found between patients who had delirium at the time of surgery (prevalent delirium) and those who developed it afterwards (incident delirium). Our findings support the hypothesis of neuroinflammation as a mechanism for delirium in patients without dementia.; (© The Author(s) 2026. Published by Oxford University Press on behalf of the Guarantors of Brain.) |
| Competing Interests: | H.Z. has served at scientific advisory boards and as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merck Sharp & Dohme, Merry Life, Nervgen, Novo Nordisk, OptoCeutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, ScandiBio Therapeutics AB, Siemens Healthineers, Triplet Therapeutics and Wave; has given lectures sponsored by AlzeCure, BioArctic, Biogen, Cellectricon, Fujirebio, LabCorp, Lilly, Novo Nordisk, Oy Medix Biochemica AB, Roche and WebMD; is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program; and is a shareholder of MicThera (outside submitted work). K.B. has served as a consultant and at advisory boards for AbbVie, AC Immune, ALZPath, AriBio, Beckman Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd., Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sunbird Bio, Sanofi and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programmes for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. The other authors report no competing interests. |
| Contributed Indexing: | Keywords: Alzheimer’s disease; CSF biomarkers; YKL-40; delirium; neuroinflammation |
| Entry Date(s): | Date Created: 20260227 Latest Revision: 20260227 |
| Update Code: | 20260227 |
| PubMed Central ID: | PMC12932948 |
| DOI: | 10.1093/braincomms/fcag005 |
| PMID: | 41756213 |
| Database: | MEDLINE |
Journal Article