Mechanisms Mediating Postoperative Neurocognitive Disorders

介导术后神经认知障碍的机制

• 批准号: 9892215
• 负责人: Susana Vacas
• 金额: $ 20.38万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892215
• 关键词: Acute; Advisory Committees; Affect; Age; Altered Level of Consciousness; Anesthesia procedures; Anesthetics; Animals; Area; Axon; Biological; Biological Markers; Blood; Brain; Brain Injuries; Brain region; CCL2 gene; Chronic; Clinical Research; Clinical Sciences; Cognition; Cognitive; Cognitive deficits; Communities; Comorbidity; Data; Data Analyses; Delirium; Dementia; Development Plans; Diagnosis; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Doctor of Philosophy; Event; Faculty; Functional disorder; Funding; Future; Goals; Growth and Development function; HMGB1 gene; Health Care Costs; Hippocampus (Brain); Human; IL6 gene; Imaging Techniques; Impaired cognition; Inflammation; Inflammatory; Innate Immune Response; Intensive Care; Interleukin-10; Intervention; Learning; Length of Stay; Leukotriene B4; Link; Magnetic Resonance Imaging; Measurable; Measures; Mechanical ventilation; Mediating; Memory; Mentors; Morbidity - disease rate; Motion; Neurocognitive Deficit; Neurons; Neurosciences; Obstructive Sleep Apnea; Operative Surgical Procedures; Patient-Focused Outcomes; Patients; Perfusion; Peripheral; Physical shape; Pike fish; Population; Populations at Risk; Postoperative Period; Prefrontal Cortex; Preventive measure; Procedures; Process; Public Health; Radiology Specialty; Recording of previous events; Reporting; Research; Research Personnel; Residual state; Risk; Risk Factors; Site; Structure; TNF gene; Techniques; Thinking; Time; Tissues; Training; Trauma; Water; base; brain morphology; brain tissue; career development; clinical development; clinical practice; cognitive change; cognitive control; cognitive recovery; cognitive testing; confusion assessment method; cytokine; data acquisition; design; experience; gray matter; hemodynamics; improved; inattention; indexing; lipoxin A4; member; mind control; mortality; neurocognitive disorder; neuroinflammation; patient population; postoperative delirium; prevent; programs; public health relevance; relating to nervous system; research study

PROJECT SUMMARY/ABSTRACT The objective of this K23 application is to provide additional training and mentored research experience for Dr. Vacas to establish herself as an independent investigator focused on understanding the mechanisms mediating Postoperative Neurocognitive Disorders (PNCD) in at-risk populations, such as patients with obstructive sleep apnea (OSA). The career development plan consists of obtaining further training in brain magnetic resonance imaging (MRI), data acquisition and analysis techniques, clinical science research, and administration of cognitive tests. To achieve training goals, Dr. Vacas has developed a focused research study and assembled an outstanding mentoring team. The primary mentor, Rajesh Kumar, PhD, is an expert in radiologic MRI techniques and interpretation, as well as neuroscience. Dr. Vacas’ co-mentors, Jeffrey Saver, MD, Daniel Cole, MD, and Nancy Pike, PhD will assist in the development of the clinical study, anesthetic management, and assessment of cognition, respectively. Dr. Vacas also assembled a Research Advisory Committee, consisting of outstanding faculty members of the UCLA research community, including Maxime Cannesson, MD, PhD (who will provide support regarding hemodynamic management), Barbara Van de Wiele, MD (who will serve as mentor in the departmental Faculty Career Development and Growth program), and David Elashoff, PhD (who will provide statistical support). The plan is designed to provide the additional training and mentored research experience needed to extend Dr. Vacas’s research program, deepen its impact by integrating the biological interface between PNCD and brain sites and compete successfully for future R01 funding. PNCD, which include postoperative delirium and both acute and long-lasting neurocognitive deficits, are a significant public health problem, leading to a cascade of deleterious complications. Although the exact pathophysiology remains poorly understood, surgery and/or anesthesia-induced neuro-inflammation can exacerbate the underlying state of chronic neuro-inflammation present within at-risk populations. The confluence of these events provide us with a window to examine and understand PNCD processes and mechanisms. Reports of links between PNCD and brain changes in humans are scarce and small in number. This project will use a consistent intraoperative anesthetic plan which will reduce variability introduced from these potentially confounding factors. The study proposes that neuro-inflammation is associated with measurable brain morphologic findings that can be discovered with non-invasive diffusion tensor imaging and blood biomarkers. In summary, the overall purpose of this study is to examine the mechanisms of brain injury contributing to PNCD in an at-risk population (OSA) undergoing surgery. The proposed study has the potential to dramatically impact clinical practice, benefiting not only OSA, but also the general surgical population. In addition, this study will also provide critical pilot data to support an R01 application for future intervention-based studies to develop preventive measures that improve patient outcomes.

项目摘要/摘要 该K23应用的目的是为提供额外的培训和修补研究经验 Vacas博士确立自己是一名专注于理解机制的独立研究者 在高危人群中介导术后神经认知疾病（PNCD），例如患者 阻塞性睡眠呼吸暂停（OSA）。职业发展计划包括获得大脑的进一步培训 磁共振成像（MRI），数据获取和分析技术，临床科学研究和 认知测试的给药。为了实现培训目标，Vacas博士开发了一项重点研究 并组建了一支杰出的心理团队。主要的精神，Rajesh Kumar，PhD是专家 放射学MRI技术和解释以及神经科学。 Vacas博士的联合官员Jeffrey Saver， 医学博士，丹尼尔·科尔（Daniel Cole），医学博士和南希·派克（Nancy Pike），博士将有助于开发临床研究，麻醉 分别管理和评估认知。 Vacas博士还组装了研究咨询 委员会，由UCLA研究社区的杰出教师组成，包括Maxime 医学博士Cannesson，博士（他将提供有关血液动力学管理的支持） 医学博士（将担任部门职业发展与成长计划的导师）和大卫 Elashoff，博士（谁将提供统计支持）。该计划旨在提供额外的培训和 迈向研究经验来扩展Vacas博士的研究计划，通过整合来加深其影响 PNCD与大脑站点之间的生物界面，并成功竞争未来的R01资金。 PNCD包括表现后的del妄以及急性和持久的神经认知缺陷，是一个 重大的公共卫生问题，导致一系列有害的并发症。虽然是确切的 病理生理学仍然很了解，手术和/或麻醉引起的神经炎症可以 加剧高危人群中存在的慢性神经炎症的潜在状态。汇合 其中，这些事件为我们提供了一个检查和理解PNCD过程和机制的窗口。 PNCD与人类大脑变化之间联系的报道稀缺，数量很小。这个项目将 使用一致的术中麻醉计划，该计划将降低这些潜在的可变性 混杂因素。研究的提案，即神经炎症与可测量的大脑有关 可以通过非侵入性扩散张量成像和血液生物标志物发现的形态学发现。 总而言之，这项研究的总体目的是检查脑损伤的机制 PNCD在高危人群中（OSA）接受手术。拟议的研究有可能显着 影响临床实践，不仅使OSA受益，而且使一般手术人群受益。此外，这项研究 还将提供关键的试点数据，以支持R01的应用程序以进行以后的研究以开发 改善患者预后的预防措施。