Preoperative Occult Neurodegeneration and Postoperative Delirium

项目主任/首席调查员(最后、第一、中间)：克罗斯比，格雷戈里·J 摘要 妄想是老年患者手术和麻醉最常见的并发症，15%-60%的患者 那些进行非心脏手术的人。这是一个主要的临床问题，因为近40%的外科手术 手术是在老年患者身上进行的，精神错乱与严重的发病率有关，包括 加速下降为痴呆症。尽管如此，术后精神错乱的原因仍不确定，其 神经发病机制尚不清楚。阿尔茨海默病的脑神经退行性病理特征 而相关的障碍即使在认知正常的老年人中也很常见，到那时甚至是轻微的症状 发展是发音的。我们假设这种先前存在的隐匿性大脑神经变性的负担 增加术后精神错乱的易感性(目标1)，增加手术和精神错乱 脑损伤(目标2)，并助长手术和精神错乱引起的炎症，后者加剧神经损伤 并增加神经退行性变(目标3)。我们将从纵向角度检验这些假说。 老年外科患者术前认知功能障碍评估及术后随访的观察研究 术后出现精神错乱和长期认知能力下降，并伴有神经变性和神经损伤 由超灵敏的血浆生物标志物和脑磁共振成像来定义。这个项目具有创新性，因为它 解决了手术和麻醉是否会导致精神错乱和持续认知的关键问题 从新开始或通过揭开或加重大脑预适应而下降，这一点很重要，因为 临床问题的严重程度(神经退行性疾病、精神错乱)，方法的实用性(血液- 基于生物标记物)，并有可能改善脆弱的老年外科患者的结果。 OMB编号0925-0001/0002(批准的第03/2020版至2023年2月28日)续页格式页

Program Director/Principal Investigator (Last, First, Middle): Crosby, Gregory J. ABSTRACT Delirium is the most common complication of surgery and anesthesia in older patients, afflicting 15-60% of those having non-cardiac procedures. This is a major clinical problem because nearly 40% of surgical procedures are performed on older patients and delirium is associated with serious morbidity, including accelerated decline to dementia. Still, the cause of postoperative delirium is uncertain and its neuropathogenesis is unknown. Cerebral neurodegenerative pathology characteristic of Alzheimer’s disease and related disorders is common even in cognitively normal older people, and by the time even mild symptoms develop is pronounced. We hypothesize that this preexisting burden of occult cerebral neurodegeneration accounts for enhanced vulnerability to postoperative delirium (Aim 1), augments surgery- and delirium-induced cerebral injury (Aim 2), and fuels surgery- and delirium-induced inflammation, which aggravates neural injury and increases neurodegeneration (Aim 3). We will test these hypotheses in a longitudinal prospective observational study of older surgical patients evaluated preoperatively for cognitive impairment and followed postoperatively for delirium and longer-term cognitive decline, with neurodegeneration and neural injury defined by ultrasensitive plasma biomarkers and cerebral MR imaging. This project is innovative because it addresses the key question of whether surgery and anesthesia produce delirium and persistent cognitive decline de novo or by unmasking or exacerbating a cerebral precondition and is significant because of the magnitude of the clinical problems (neurodegenerative disease, delirium), practicality of the approach (blood- based biomarkers), and potential to improve the outcomes of vulnerable older surgical patients. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page