持续谵妄与脑脊液中的神经元损伤标志物有关。

IF 4.1 Q1 CLINICAL NEUROLOGY Brain communications Pub Date : 2024-09-18 eCollection Date: 2024-01-01 DOI:10.1093/braincomms/fcae319
Alex Tsui, Benjamin Johnstone, Amanda Heslegrave, Henrik Zetterberg, Leiv Otto Watne, Bjørn Erik Neerland, Maria Krogseth, Colm Cunningham, Alasdair MacLullich, Graciela Muniz Terrera, Daniel Davis, Gideon Caplan
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引用次数: 0

摘要

谵妄与未来长期认知功能障碍的风险有关,但神经元损伤标志物在多大程度上可能与痴呆症不同或共享,尚有待全面描述。我们研究了持续谵妄临床队列中痴呆、星形细胞增多和神经元损伤的脑脊液生物标志物,并将其与门诊记忆门诊样本进行了比较。我们的目的是确定不同的生物标志物变化模式是否暗示了与谵妄相关的神经元损伤的特定机制,而不是合并痴呆所造成的损伤。我们从澳大利亚悉尼威尔士亲王医院招募了 35 名参与者。其中包括谵妄持续至少5天的住院病人(15人,10人患有潜在痴呆症)和门诊记忆诊所的患者(20人,17人患有痴呆症)。脑脊液检测项目如下:淀粉样蛋白-β42、淀粉样蛋白-β40、磷酸化tau181、神经丝蛋白轻链和胶质纤维酸性蛋白。我们采用倾向得分匹配法分别估算了持续性谵妄(无论是否存在潜在痴呆)和痴呆(无论是否叠加谵妄)中每个标准化脑脊液生物标志物的效应大小。与无谵妄的患者相比,持续性谵妄与胶质纤维酸性蛋白(每转换标准差归一化系数,β = 0.85;95% 置信区间:0.03-1.68)和神经丝轻链(β = 1.1;95% 置信区间:0.5-1.6)升高有关,但与磷酸化 tau181 无关。与非痴呆症患者相比,痴呆症患者的神经胶质纤维酸性蛋白、神经丝蛋白轻链和磷酸化tau181都增加到了预期水平,前两种生物标志物的水平与持续性谵妄患者的水平相当[神经胶质纤维酸性蛋白(β = 1.54;95% 置信区间:1.05-2.0)和神经丝蛋白轻链(β = 0.65;95% 置信区间:0.24-1.1)]。持续谵妄与脑脊液生物标志物的变化有关,但不一定归因于痴呆。这些研究结果证明,谵妄可能与痴呆病理生理学之外的直接神经元损伤有关。这种神经元损伤是否涉及星形胶质细胞功能障碍或直接轴突损伤,这两种可能性都存在。未来还需要对谵妄中的急性脑损伤进行研究。
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Persistent delirium is associated with cerebrospinal fluid markers of neuronal injury.

Delirium is associated with the risk of future long-term cognitive impairment, but the degree to which markers of neuronal injury may be distinct or shared with dementia has yet to be comprehensively described. We investigated CSF biomarkers of dementia, astrocytosis and neuronal damage in a clinical cohort with persistent delirium, comparing them with an outpatient memory clinic sample. Our aim was to determine if different patterns of biomarker changes could implicate specific mechanisms for delirium-related neuronal injury over and above that attributable to comorbid dementia. We recruited 35 participants from the Prince of Wales Hospital, Sydney, Australia. We included inpatients with delirium persisting for at least 5 days (n = 15, 10 with underlying dementia) and participants from outpatient memory clinics (n = 20, 17 with dementia). CSF assays were as follows: amyloid-β42, amyloid-β40, phosphorylated tau181, neurofilament light chain and glial fibrillary acidic protein. We used propensity score matching to estimate effect sizes for each standardized CSF biomarker separately for persistent delirium (irrespective of underlying dementia) and dementia (irrespective of superimposed delirium). Compared with individuals without delirium, persistent delirium was associated with elevated glial fibrillary acidic protein (normalized coefficient per transformed standard deviation, β = 0.85; 95% confidence interval: 0.03-1.68) and neurofilament light chain (β = 1.1; 95% confidence interval: 0.5-1.6), but not phosphorylated tau181. Compared with individuals without dementia, glial fibrillary acidic protein, neurofilament light chain and phosphorylated tau181 were all increased to expected levels in dementia cases, with the former two biomarkers at levels comparable to those seen in persistent delirium [glial fibrillary acidic protein (β = 1.54; 95% confidence interval: 1.05-2.0) and neurofilament light chain (β = 0.65; 95% confidence interval: 0.24-1.1)]. Persistent delirium was linked with changes in CSF biomarkers not necessarily attributable to dementia. These findings support the potential that delirium is associated with direct neuronal injury independent of dementia pathophysiology. Whether this neuronal injury involves astrocyte dysfunction or direct axonal damage are both possibilities. Future work examining acute brain injury in delirium is needed.

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