Relationship between CNS Tau burden and perioperative neurocognitive disorder

CNS Tau负荷与围手术期神经认知障碍的关系

• 批准号: 10232053
• 负责人: Roderic G Eckenhoff
• 金额: $ 21.92万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10232053
• 关键词: Acute; Address; Alzheimer' s Disease; Anesthesia procedures; Binding; Biological Markers; Blood; Brain; Brain imaging; Cerebrospinal Fluid; Clinic; Clinical; Clinical Research; Cognition; Cognitive; Communication; Complication; Data; Data Analyses; Delirium; Dementia; Deposition; Educational Materials; Elderly; Elements; Enrollment; Evaluation; Financial compensation; Goals; Hemorrhage; Human; Impaired cognition; Impairment; Incentives; Inflammation; Inflammatory; Infrastructure; Leadership; Learning; Ligand Binding; Ligands; Longitudinal cohort; Measures; Memory; Neurocognitive; Neurofibrillary Tangles; Neuropsychological Tests; Observational Study; Operative Surgical Procedures; Outcome; Pathology; Patients; Perioperative; Peripheral; Phase; Pilot Projects; Positron-Emission Tomography; Postoperative Period; Pre-Clinical Model; Probability; Psychometrics; Recovery; Reporting; Rest; Risk; Screening procedure; Site; Spine surgery; Surveys; Tauopathies; Testing; Tracer; Vertebral column; Work; age group; cognitive testing; cohort; experience; functional outcomes; inflammatory marker; neurocognitive disorder; neuroinflammation; neuropathology; older patient; postoperative delirium; pre-clinical; primary outcome; prospective; radiotracer; secondary outcome; tau Proteins; tau aggregation; tau-1

Summary: Post-operative neurocognitive disorder is common after all forms of surgery in older adults. The mechanisms are multifactorial, and probably require pre-existing neuropathology, whether symptomatic or not. Preclinical and human CSF studies suggests that anesthesia and surgery elicits an increment in CNS tauopathy, which may accelerate any pre-existing neuropathology and produce a risk of delirium and the commonly reported changes in cognition. We here propose an observational clinical study at two sites to determine whether pre-operative CNS tauopathy as reflected by PET imaging predicts delirium and other cognitive and functional outcomes. This is important since these outcomes may also predict Alzheimer Disease and other dementias. Further, we will determine if anesthesia and spine surgery produces a change in brain tau burden in older adults, as compared to control, non-operative patients. We will also measure pre- and post-surgery blood biomarkers of inflammation, as well as cognitive status using detailed neuropsychological tests. The primary aims of this phased study is to first establish an integrated team, infrastructure and provide preliminary data supporting feasibility, and then to embark on a two-site observational study in approximately 30 patients and 30 controls to address the above goals.

总结：术后神经认知障碍在老年人所有形式的手术后都很常见。的 机制是多因素的，可能需要预先存在的神经病理学，无论是症状性的还是 没有临床前和人体CSF研究表明，麻醉和手术可增加CNS tau蛋白病，这可能会加速任何预先存在的神经病理学，并产生谵妄的风险， 通常报告的认知变化。我们在此提出在两个地点进行观察性临床研究， 确定PET成像所反映的术前CNS tau病变是否可预测谵妄和其他 认知和功能结果。这很重要，因为这些结果也可以预测阿尔茨海默病 疾病和其他痴呆症。此外，我们将确定麻醉和脊柱手术是否会产生 与对照、非手术患者相比，老年人脑tau蛋白负荷的变化。我们还将 测量术前和术后炎症的血液生物标志物，以及使用详细的 神经心理学测试这项分阶段研究的主要目的是首先建立一个综合小组， 基础设施，并提供初步的数据支持的可行性，然后走上两个网站 在大约30名患者和30名对照中进行的观察性研究，以实现上述目标。