Bratseth Vibeke, Watne Leiv Otto, Neerland Bjørn Erik, Halaas Nathalie Bodd, Pollmann Christian Thomas, Karabeg Adi, Odegaard Olav Tobias, Sydnes Kristian, Zetterberg Henrik, Seljeflot Ingebjørg, Helseth Ragnhild
Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, Oslo 0424, Norway.
Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, Oslo 0424, Norway.
Brain Commun. 2024 Dec 16;7(1):fcae452. doi: 10.1093/braincomms/fcae452. eCollection 2025.
Delirium is a neuropsychiatric syndrome commonly presenting during acute illness. 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 ( = 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 Bærum Hospital. Delirium was assessed daily, pre- and postoperatively. Cognitively healthy adults ( = 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® 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 ( = 68) versus without ( = 221) delirium after adjusting for age and sex (70 (59, 84) versus 62 (53, 77) ng/ml, = 0.037) and 601 (504, 684) versus 508 (458, 572) ng/ml, = 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 ( = 0.441, < 0.001). The correlation was stronger in those with delirium ( = 0.468, < 0.001) and strongest in delirious patients without dementia ( = 0.765, = 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.
谵妄是一种常见于急性疾病期间的神经精神综合征。谵妄的病理生理学尚不清楚，但有研究表明神经炎症在其中发挥作用。在这项横断面研究中，我们旨在调查血清和脑脊液中的游离DNA以及中性粒细胞胞外诱捕网的标志物是否与谵妄和神经损伤相关，神经损伤通过神经丝轻链进行评估。奥斯陆大学医院、迪亚科内赫姆医院、阿克什胡斯大学医院和贝鲁姆医院纳入了491例髋部骨折患者，年龄中位数（第25、75百分位数）为83（74，88）岁，女性占69%。在术前和术后每天对谵妄进行评估。纳入32名认知健康的成年人作为对照，年龄中位数（第25、75百分位数）为75（70，77）岁，女性占53%。使用荧光核酸染料Quant-iT PicoGreen®测量血清和脑脊液中的游离DNA。通过酶联免疫吸附测定法分析血清中的髓过氧化物酶-DNA和瓜氨酸化组蛋白H3。髋部骨折患者血液中的游离DNA和中性粒细胞胞外诱捕网水平显著高于认知健康的对照组。在无痴呆的髋部骨折患者中，校正年龄和性别后，发生谵妄（n = 68）的患者脑脊液和血清中的游离DNA水平显著高于未发生谵妄（n = 221）的患者（分别为70（59，84）对62（53，77）ng/ml，P = 0.037）和601（504，684）对508（458，572）ng/ml，P = 0.007）。在整个髋部骨折队列中，校正年龄和性别后脑脊液中游离DNA水平与神经丝轻链水平显著相关（r = 0.441，P < 0.001）。这种相关性在发生谵妄的患者中更强（r = 0.468，P < 0.001），在无痴呆的谵妄患者中最强（r = 0.765，P = 0.045）。在无痴呆的谵妄患者中，脑脊液和血清中的游离DNA水平显著更高。游离DNA与神经丝轻链之间的关联表明在谵妄期间游离DNA和神经元损伤同时发生。
