Preoperative Occult Neurodegeneration and Postoperative Delirium

术前隐匿性神经变性和术后谵妄

基本信息

批准号：
10367616
负责人：
GREGORY CROSBY
金额：
$ 89.45万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-15 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10367616
关键词：
Acute Address Age Age-Years Alzheimer&apos s Disease Amyloidosis Anesthesia procedures Biological Markers Brain CD14 gene Cerebrum Characteristics Clinical Cognition Cognitive Confusion Data Delirium Dementia Development Diagnosis Disease Distress Elderly Future Glial Fibrillary Acidic Protein Immune response Impaired cognition Impairment Inflammation Inflammatory Response Injury Lead Light Magnetic Resonance Imaging Measures Morbidity - disease rate Nerve Degeneration Neurobehavioral Manifestations Neurobiology Neurodegenerative Disorders Neuropathogenesis Observational Study Operative Surgical Procedures Outcome Pathogenicity Pathology Patients Perioperative Care Plan B Plasma Positron-Emission Tomography Postoperative Period Predisposition Prevalence Principal Investigator Procedures Proteome Proxy Recovery of Function Research Risk Assessment Risk Factors Severities Spinal Puncture Spine surgery Surgical complication Symptoms Syndrome Tauopathies Testing Time Validation Work axon injury blood-based biomarker cerebral atrophy cost human old age (65+)improved improved outcome innovation magnetic resonance imaging biomarker monocyte nerve injury neurofilament neuropathology novel older patient postoperative delirium primary outcome programs prospective relating to nervous system risk prediction secondary outcome surgical risk systemic inflammatory response tau Proteins transcriptome

项目摘要

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

计划总监/首席研究员（最后，第一，中间）：Crosby，Gregory J. 抽象的 del妄是老年患者中最常见的手术和麻醉并发症，折磨了15-60％那些有非心脏程序的人。这是一个主要的临床问题，因为几乎40％的手术对老年患者进行程序，del妄与严重的发病率有关，包括加速降低痴呆症。尽管如此，术后del妄的原因还是不确定的神经病发生尚不清楚。阿尔茨海默氏病的脑神经退行性病理学特征即使在认知正常的老年人中，相关疾病也很常见，甚至在轻度症状时发展是明显的。我们假设这种神秘的脑神经退行性的燃烧术后del妄的脆弱性增加（AIM 1），增强手术和ir妄诱导脑损伤（AIM 2），并为手术和ir妄诱导的感染燃料加剧了神经损伤并增加神经变性（AIM 3）。我们将在纵向前瞻性中检验这些假设术前评估认知障碍的老年手术患者的观察性研究，随后神经退行性和神经损伤的del妄和长期认知能力下降的典范由超敏感的血浆生物标志物和脑MR成像定义。这个项目是创新的，因为它解决手术和麻醉是否产生ir妄和持续认知的关键问题从头拒绝或通过揭露或加剧脑前提条件，并且很重要，因为临床问题的大小（神经退行性疾病，del妄），方法的实用性（血液 - 基于生物标志物），并有可能改善脆弱的老年手术患者的结局。 OMB No. 0925-0001/0002（Rev. 03/2020通过02/28/2023批准）页面延续格式页面