Bowman Emily Margaret Louise, McAuley Daniel F, McGuinness Bernadette, Passmore Anthony P, Beverland David, Zetterberg Henrik, Schott Jonathan M, Heslegrave Amanda, Veleva Elena, Laban Rhiannon, Sweeney Aoife, Cunningham Emma L
Centre for Public Health, Institute of Clinical Science, Royal Victoria Hospital, Queen's University Belfast, Belfast, UK.
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
Alzheimers Dement. 2025 Jul;21(7):e70516. doi: 10.1002/alz.70516.
Delirium has heterogeneous etiologies and clinical presentations and is often associated with poor outcomes. Its pathophysiological mechanisms remain largely hypothetical and without targeted pharmacological treatment. This work investigates subphenotypes of patients undergoing delirium assessment based on clinical features and fluid biomarkers.
We performed latent class analysis of an observational cohort of older adults undergoing elective surgery.
Two classes were identified, both containing individuals experiencing delirium symptoms, with a higher number in Class 1 (p < 0.001). Class 1 were older, less educated, and had more depression (p < 0.001). They performed worse in all pre-operative cognitive assessments (p < 0.001) and had more markers of central nervous system damage: cerebrospinal fluid glial fibrillary acidic protein, neurofilament light chain, and soluble triggering receptor expressed on myeloid cells 2 (p < 0.001); plasma phosphorylated tau (p = 0.024); and amyloid beta 42/40 ratio (p < 0.001). Class 2 experienced more pain (p = 0.006) and received more morphine equivalents (p = 0.018).
Delirium and neighboring phenotypes should be investigated thoroughly in the newly dawning era of precision medicine, to establish novel treatments.
Latent class analysis identified two subphenotypes of patients. Both groups contained patients with delirium or its individual symptoms. Groups differed by age, education, depression, independent living, and pain levels. Groups differed by pre-operative and post-operative cognition. Groups differed by biomarker levels of neurodegeneration and neuronal injury.
谵妄病因和临床表现具有异质性，且常与不良预后相关。其病理生理机制大多仍为假设，尚无针对性的药物治疗。本研究基于临床特征和体液生物标志物，对接受谵妄评估的患者亚表型进行调查。
我们对接受择期手术的老年观察队列进行了潜在类别分析。
确定了两个类别，均包含有谵妄症状的个体，其中第1类人数更多（p < 0.001）。第1类患者年龄更大、受教育程度更低且抑郁程度更高（p < 0.001）。他们在所有术前认知评估中的表现更差（p < 0.001），且有更多中枢神经系统损伤标志物：脑脊液胶质纤维酸性蛋白、神经丝轻链和髓样细胞上表达的可溶性触发受体2（p < 0.001）；血浆磷酸化tau蛋白（p = 0.024）；以及淀粉样β蛋白42/40比值（p < 0.001）。第2类患者经历的疼痛更多（p = 0.006），接受的吗啡等效剂量更多（p = 0.018）。
在精准医学崭露头角的新时代，应深入研究谵妄及相关表型，以确立新的治疗方法。
潜在类别分析确定了患者的两种亚表型。两组均包含有谵妄或其个别症状的患者。两组在年龄、教育程度、抑郁、独立生活能力和疼痛程度方面存在差异。两组在术前和术后认知方面存在差异。两组在神经退行性变和神经元损伤的生物标志物水平方面存在差异。
