The association of selected biomarkers with postoperative delirium (POD) and postoperative cognitive dysfunction (POCD): modelling biomarkers from the PAWEL study (patient safety, cost-effectiveness, and quality of life after elective procedures in older

妄想症是一种神经精神综合征，以注意力、意识和认知的急性障碍为特征，由潜在的医学状况引起。它与多种不良的短期和长期结果有关，包括延长住院时间和新的机构，以及增加发病率和死亡率。在择期手术后，老年患者发生术后精神障碍(POD)和术后认知功能障碍(POCD)的风险增加。尽管识别了临床危险因素，并将它们整合到预测算法中，但不可能确切地预测单个患者是否会发展为POD或POCD。血液生物标志物有助于更好地识别高危患者，同时有助于更好地了解POD的发病机制，从而为有针对性的治疗干预提供信息。最近的研究表明，神经炎性和神经退行性疾病是最有前景的生物标志物。在Pawel研究(Pawel：Patientensicherheit，Wirtschaftlichkeit and Lebensqualität；患者安全性、成本效益和生活质量，由Innovationsfond资助)中，我们能够在一组楔形分组随机试验中展示出跨部门、多模式干预的有效性，该干预措施可减少接受不同择期外科手术但未接受心脏手术的老年患者术后精神障碍的发生率和精神错乱的天数。除了主要的资助外，我们在一项子研究中收集了约350名患者的血液样本，并已经分析了标志物NFL、GFAP、Abeta42/40、S100B、NSE和IL-6。与其他已发表的关于精神错乱的生物标志物研究相比，这是最大的样本组之一。这项建议的总体目的是为了更好地了解哪些生物标记物(例如，神经退行性变与神经炎性)与POD和相关POCD的发病与严重程度相关，以便描述POD和POCD的预测标志和发病机制。为此，我们计划确定更多的神经炎性和神经退行性生物标志物，并使用复杂的统计分析，包括潜在类别回归分析和结构方程建模(SEM)。为了更好地理解POD与神经退行性和炎症性生物标记物的变化相对应的生物学机制，我们建议对与痴呆发病相关或减缓其发病机制的潜在生物标记物进行表征，以确定潜在的药物干预靶点。我们还将确定这些生物标志物的水平和变化是否可以提高POCD的临床风险预测分数。我们的结果将有助于进一步了解老年患者术后精神障碍的机制，最终导致更好的预测和针对性的干预措施。

Delirium is a neuropsychiatric syndrome characterized by acute disturbances in attention, awareness and cognition and caused by an underlying medical condition. It is associated with multiple poor short and long-term outcomes, including prolonged hospital stay as well as new institutionalization, and increased morbidity and mortality. After elective surgery, elderly patients are at increased risk of developing postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). Despite the identification of clinical risk factors and their integration in predictive algorithms, it is not possible to predict with certainty whether an individual patient will develop POD or POCD. Blood biomarkers could help to both better identify high-risk patients and at the same time help to better understand pathogenic mechanisms of POD and thus inform targeted therapeutic interventions. Recent studies identify neuroinflammatory and neurodegenerative biomarkers as the most promising biomarkers. In the PAWEL-study (PAWEL: Patientensicherheit, Wirtschaftlichkeit und Lebensqualität; patient safety, cost-effectiveness and quality of life, funded by the Innovationsfond) we were able to show in a stepped wedge cluster randomized trial the effectiveness of a cross-sectoral and multimodal intervention to reduce the prevalence of postoperative delirium occurrence and days with delirium in older patients undergoing different elective surgical procedures but not cardiac procedures. Independent of the primary funding, we collected blood samples in a substudy from ~350 patients and already analysed the markers NFL, GFAP, Abeta 42/40, S100B, NSE and IL-6. Compared to other published biomarker studies in delirium this is one of the largest sample sets. The overall aim of this proposal is to gain a better understanding of which biomarkers (e.g., neurodegenerative vs. neuroinflammatory) are associated with the onset versus severity of POD and associated POCD in order to delineate predictive markers and pathogenic mechanisms of POD and POCD. To do so, we plan to determine additional neuroinflammatory and neurodegenerative biomarkers and employ complex statistical analyses including latent class regression analyses and structural equation modelling (SEM). We propose to characterize latent classes of biomarkers associated with or moderating the pathogenesis of delirium in order to gain a better understanding of the biological mechanisms of POD that correspond to changes in neurodegenerative and inflammatory biomarkers with the overall aim of identifying potential targets for pharmacological interventions. We will also determine whether level and change in these biomarkers can improve clinical risk prediction scores for POCD. Our results will help to further understand the mechanisms underlying postoperative delirium in elderly patients, ultimately leading to better prediction and tailored intervention for both delirium and POCD.