Shared Pathophysiology of Postoperative Delirium and Alzheimer's Disease and Related Dementias

术后谵妄和阿尔茨海默病及相关痴呆的共同病理生理学

基本信息

批准号：
9902270
负责人：
SARINNAPHA VASUNILASHORN
金额：
$ 11.32万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902270
关键词：
Acute Address Adult Age Aging Alleles Alzheimer&apos s disease related dementia Apolipoprotein E Area Biological Markers Blood - brain barrier anatomy Brain C-reactive protein CHI3L1 gene Cerebrospinal Fluid Chitinase Clinical Cognition Competence Confusion Consensus Data Analyses Data Collection Data Reporting Delirium Dementia Elderly Enrollment Epidemiology Foundations Functional disorder Funding Genetic Genetic Markers Genetic Predisposition to Disease Genetic Risk Genotype Glial Fibrillary Acidic Protein Goals Hospitals Impaired cognition Incidence Individual Infection Inflammation Inflammatory Interleukin-6 Joints K-Series Research Career Programs Knowledge Light Link Measures Mentored Research Scientist Development Award Methods Microglia Modeling Neurocognitive Neurologic Dysfunctions Neuronal Injury Operative Surgical Procedures Orthopedics Pathway interactions Patients Peripheral Plasma Plasma Proteins Population Positioning Attribute Predisposing Factor Proteins Protocols documentation Quality of life Research Research Personnel Research Project Grants Resources Risk Risk Factors Risk Marker Sampling Series Severities Syndrome Time Training Training Support United States National Institutes of Health Work Writing acute stress apolipoprotein E-4 base biobank biological adaptation to stress career career development cognitive function cohort cost experience inflammatory marker innovation knowledge base neurofilament neuroinflammation neuron loss neuroprotection novel novel marker older patient patient oriented postoperative delirium postoperative recovery prevent programs protein biomarkers secondary analysis skill acquisition systemic inflammatory response targeted treatment translational scientist

项目摘要

PROJECT SUMMARY/ABSTRACT This K01 Career Development Award will support the training and career development of a junior investigator, Dr. Sarinnapha Vasunilashorn, in patient-oriented aging research. The overall goal of the proposal is to provide Dr. Vasunilashorn with critical skills and development of experience and competence as an independent, translational researcher in delirium and Alzheimer's Disease and Related Dementias (ADRD). Specific training goals include: 1) obtaining experience in primary data collection within a clinical setting, 2) expansion of her analytic skillset in advanced longitudinal methods and genetic data analysis, and 3) building an in-depth knowledge base of ADRD. These training goals will be conducted in coordination with a set of specific research projects based on Dr. Vasunilashorn's preliminary data that reports on the association between plasma inflammatory markers and the incidence and severity of postoperative delirium in older patients without ADRD undergoing non-cardiac surgery. Delirium and ADRD have strong epidemiological associations: ADRD has long-been recognized as a risk factor for delirium, and recently delirium has been implicated as a risk factor for incident ADRD. Although this points to a clear link between delirium and ADRD, the shared pathophysiology underlying these relationships remains largely unknown. In the proposed K01 Specific Aims, Dr. Vasunilashorn will address this gap in knowledge and substantially extend her preliminary studies that have focused only on plasma-based markers of inflammation by examining whether both plasma and cerebrospinal fluid (CSF)-based measures of neuroinflammation and neuronal injury are associated with postoperative delirium, long-term cognitive decline, and incident ADRD, and evaluate whether genetic risk modifies these associations. These studies will leverage the considerable resources of: 1) the NIA-funded program project, the Successful Aging after Elective Surgery Study (SAGES; P01AG031720), and 2) the Healthier Postoperative Recovery Study (HiPOR; R21AG048600). This proposal is highly novel in examining markers of neuroinflamamtion and neuronal injury that will advance our understanding of the pathophysiologic mechanisms underlying the delirium-ADRD relationship, a largely underexplored area that represents a top priority area of the NIH (PAR-17-038). Importantly, the results will inform pathophysiologically targeted treatment for inflammation to provide neuroprotection and identify important variables to refine delirium risk prediction strategies thereby potentially preventing delirium and reducing ADRD. Ultimately, this work will pave the way and provide the foundation for the launch of Dr. Vasunilashorn's independent research career that will explore the pathophysiologic linkages of delirium and ADRD, two major threats to the independence and quality of life of all older adults.

项目概要/摘要 K01 职业发展奖将支持初级研究员的培训和职业发展， Sarinnapha Vasunilashorn 博士，从事以患者为导向的衰老研究。该提案的总体目标是提供 Vasunilashorn 博士拥有关键技能以及作为独立、谵妄和阿尔茨海默病及相关痴呆症 (ADRD) 的转化研究员。具体培训目标包括：1）获得临床环境中主要数据收集的经验，2）扩展她的能力先进纵向方法和遗传数据分析的分析技能，以及3）建立深入的 ADRD 知识库。这些培训目标将与一系列具体的协调一致进行基于 Vasunilashorn 博士的初步数据的研究项目报告了两者之间的关联血浆炎症标志物与老年患者术后谵妄的发生率和严重程度 ADRD 接受非心脏手术。谵妄和 ADRD 具有很强的流行病学关联：ADRD 长期以来一直被认为是谵妄的危险因素，最近谵妄也被认为是一种风险 ADRD 事件的因素。尽管这表明谵妄和 ADRD 之间存在明显的联系，但共同的这些关系背后的病理生理学仍然很大程度上未知。在拟议的 K01 具体目标中， Vasunilashorn 博士将解决这一知识空白，并大幅扩展她的初步研究，这些研究已经通过检查血浆和脑脊髓是否都集中于基于血浆的炎症标志物基于液体（CSF）的神经炎症和神经元损伤测量与术后相关谵妄、长期认知能力下降和 ADRD 事件，并评估遗传风险是否会改变这些协会。这些研究将利用以下方面的大量资源：1) NIA 资助的计划项目，择期手术后成功老龄化研究 (SAGES; P01AG031720)，以及 2) 更健康术后恢复研究（HiPOR；R21AG048600）。该提案在检查标记物方面非常新颖神经炎症和神经元损伤将增进我们对病理生理学的理解谵妄-ADRD 关系的潜在机制，这是一个很大程度上未被充分探索的领域，代表了一个顶级领域 NIH 的优先领域 (PAR-17-038)。重要的是，结果将为病理生理学目标提供信息治疗炎症以提供神经保护并确定重要变量以改善谵妄风险预测策略从而有可能预防谵妄并减少 ADRD。最终，这项工作将为为 Vasunilashorn 博士开启独立研究生涯奠定了基础探索谵妄和 ADRD 的病理生理联系，这两个对独立性和精神障碍的主要威胁所有老年人的生活质量。