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The pathophysiology of delirium is unknown, but neuroinflammation is suggested to play a role. In this cross-sectional study, we aimed to investigate whether cell-free DNA and markers of neutrophil extracellular traps in serum and CSF were associated with delirium and neuronal damage, assessed by neurofilament light chain. Hip fracture patients (n = 491) with a median (25, 75 percentiles) age of 83 (74, 88) years and 69% females were enrolled at Oslo University Hospital, Diakonhjemmet Hospital, Akershus University Hospital and B\u00e6rum Hospital. Delirium was assessed daily, pre- and postoperatively. Cognitively healthy adults (n = 32) with a median (25, 75 percentiles) age of 75 (70, 77) years and 53% females were included as controls. Cell-free DNA was measured by using the fluorescent nucleic acid stain Quant-iT PicoGreen\u00ae in serum and CSF. Myeloperoxidase-DNA and citrullinated histone H3 were analysed by enzyme-linked immunosorbent assay in serum. Hip fracture patients have significantly higher levels of cell-free DNA and neutrophil extracellular traps in blood than cognitively healthy controls. In hip fracture patients without dementia, cell-free DNA in CSF and serum was significantly higher in patients with (n = 68) versus without (n = 221) delirium after adjusting for age and sex (70 (59, 84) versus 62 (53, 77) ng\/ml, P = 0.037) and 601 (504, 684) versus 508 (458, 572) ng\/ml, P = 0.007, respectively). In the total hip fracture cohort, CSF levels of cell-free DNA and neurofilament light chain were significantly correlated after adjusting for age and sex (r = 0.441, P &amp;lt; 0.001). The correlation was stronger in those with delirium (r = 0.468, P &amp;lt; 0.001) and strongest in delirious patients without dementia (r = 0.765, P = 0.045). In delirious patients without dementia, significantly higher levels of cell-free DNA in CSF and serum were shown. The association between cell-free DNA and neurofilament light chain suggest simultaneous release of cell-free DNA and neuronal damage during delirium.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae452","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T18:19:42Z","timestamp":1734373182000},"source":"Crossref","is-referenced-by-count":2,"title":["Increased cell-free DNA in CSF and serum of hip fracture patients with delirium"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2775-4219","authenticated-orcid":false,"given":"Vibeke","family":"Bratseth","sequence":"first","affiliation":[{"name":"Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital , Oslo 0424 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiv Otto","family":"Watne","sequence":"additional","affiliation":[{"name":"Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital , Oslo 0424 ,","place":["Norway"]},{"name":"Department of Geriatric Medicine, Akershus University Hospital , L\u00f8renskog 1478 ,","place":["Norway"]},{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo , Oslo 0318 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn Erik","family":"Neerland","sequence":"additional","affiliation":[{"name":"Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital , Oslo 0424 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie Bodd","family":"Halaas","sequence":"additional","affiliation":[{"name":"Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital , Oslo 0424 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Thomas","family":"Pollmann","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Akershus University Hospital , L\u00f8renskog 1478 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Karabeg","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Akershus University Hospital , Kongsvinger 2381 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olav Tobias","family":"Odegaard","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Akershus University Hospital , Kongsvinger 2381 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Sydnes","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Diakonhjemmet Hospital , Oslo 0319 ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg , M\u00f6lndal 40530 ,","place":["Sweden"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal 40530 ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , London WC1H9BT ,","place":["UK"]},{"name":"UK Dementia Research Institute at UCL , London WC1H9BT ,","place":["UK"]},{"name":"Hong Center for Neurodegenerative Diseases , Hong Kong HKG ,","place":["China"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53707 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