Cognitive decline after hospitalization in older adults: predictors and pathogenesis

 描述(由申请人提供)：这是拉什阿尔茨海默病中心(RADC)的助理教授和流行病学家Bryan D.James博士为K01奖项提出的申请。这个K01的总体目标是建立一个知识基础，使詹姆斯博士能够实现他的长期目标，即在衰老的认知衰退的原因和预防方面确立自己作为独立调查者的地位。这项研究的直接目标和应用目标是了解住院治疗如何以及为什么会导致一些老年人的认知能力下降。该奖项将补充流行病学方法和研究伦理的强大背景，为詹姆斯博士提供必要的培训，以填补他在三个关键领域的知识空白：1)了解临床痴呆症和老年人认知障碍的评估；2)利用医疗索赔记录进行研究的专业知识；3)了解痴呆症的神经生物学和神经病理学。为了在这三个领域取得能力，詹姆斯博士组建了一个由与这些实质性领域相对应的互补领域的专家组成的指导小组。主要导师是RADC的高级神经病理学家朱莉·施奈德博士，她有多年的指导经验，曾担任NIA-N-K委员会的成员和负责人。其他三位导师分别是神经病学家、RADC主任戴维·A·贝内特博士；RADC高级神经心理学家、受人尊敬的认知衰老研究专家罗伯特·S·威尔逊博士；以及老年病学家、拉什记忆诊所(Rush Memory Clinic)医学主任拉杰·C·沙阿博士。此外，James博士还组建了一个专家咨询委员会，其专家包括：危重护理和认知障碍(范德比尔特大学的E.Wesley Ely博士)、神经危重护理(Thomas Bleck博士，拉什大学医学中心)、将医疗保险记录用于研究(Jonathan Skinner博士，达特茅斯大学)和神经成像(Konstantinos Arfan akis博士，RADC和伊利诺伊理工学院)。拟议的研究项目将调查老年人住院后的认知衰退；特别是这种现象的院前危险因素(目标1)、负责任的医院特征(目标2)和发病机制(目标3)。这项创新的研究设计将整合来自老龄化临床-病理队列-Rush Memory and Aging Project的纵向认知、临床、神经病理和神经成像数据，以及提供十多年详细住院信息的联邦医疗保险索赔记录。James博士将利用记忆和老龄化项目的现有数据和基础设施，以及之前为该项目获得的现有11年的联邦医疗保险记录。此外，詹姆斯博士建议从医疗保险和医疗保险服务中心(CMS)再获得6年的医疗保险数据。在目标1中，詹姆斯博士将检查住院事件后认知能力加速下降的院前风险因素，并制定这种下降的风险概况。在目标2中，他将研究特定的医院特征与认知能力加速下降的关系，包括ICU住院、手术、麻醉、败血症和精神错乱。在目标3中，他将调查痴呆症的常见神经病理，如阿尔茨海默病和脑血管疾病，是否会导致住院后认知能力下降。这项研究的结果将成为在资助期结束前向国家卫生研究院提出R01拨款申请的基础。

 DESCRIPTION (provided by applicant): This is an application for a K01 award by Dr. Bryan D. James, an assistant professor and epidemiologist at the Rush Alzheimer's Disease Center (RADC). The overall goal of this K01 is to build a foundation of knowledge that will enable Dr. James to achieve his long-term goal of establishing himself as an independent investigator in the causes and prevention of cognitive decline in aging. The immediate goal, and the objective of the research application, is to understand how and why hospitalization leads to cognitive decline in some older persons. The award will supplement a strong background in epidemiologic methods and research ethics by providing Dr. James with the training necessary to fill gaps in his knowledge in three critical areas: 1) understanding clinical dementia and assessment of cognitive impairment in older adults, 2) expertise in using medical claims records for research, 3) comprehending the neurobiology and neuropathology of dementia. To achieve competence in these three areas, Dr. James has assembled a mentoring team of experts in complementary fields corresponding to these substantive areas. The primary mentor is Dr. Julie Schneider, the senior neuropathologist of the RADC, who has many years of mentorship experience and has served on and headed the NIA-N K committee. The other three mentors are Dr. David A. Bennett, a neurologist and the Director of the RADC; Dr. Robert S. Wilson, the RADC senior neuropsychologist and respected expert in the study of cognitive aging; and Dr. Raj C. Shah, a geriatrician and the medical director of the Rush Memory Clinic. In addition, Dr. James has assembled an Advisory Committee of experts in: critical care and cognitive impairment (Dr. E. Wesley Ely, Vanderbilt University), neurocritical care (Dr. Thomas Bleck, Rush University Medical Center), use of Medicare records for research (Dr. Jonathan Skinner, Dartmouth University), and neuroimaging (Dr. Konstantinos Arfanakis, RADC and Illinois Institute of Technology). The proposed research project will investigate cognitive decline after hospitalization in older adults; in particular, the prehospital risk factors (Aim 1), responsible hospital characteristics (Aim 2), and pathogenesis (Aim 3) of this phenomenon. The innovative study design will integrate longitudinal cognitive, clinical, neuropathologic, and neuroimaging data from a clinical-pathologic cohort of aging, the Rush Memory and Aging Project, with Medicare claims records providing detailed hospitalization information over more than a decade. Dr. James will leverage the existing data and infrastructure of the Memory and Aging Project and the existing 11 years of Medicare records previously obtained for this project. In addition, Dr. James proposes to obtain 6 more years of Medicare data from the Center for Medicare and Medicare Services (CMS). In Aim 1, Dr. James will examine the prehospital risk factors of accelerated cognitive decline after incident hospitalization and develop a risk profile for such decline. In Aim 2, he will examine the relationship of specific hospital characteristics with accelerated cognitive decline, including ICU stays, surgery, anesthesia, sepsis, and delirium. In Aim 3, he will investigate whether common neuropathologies of dementia, such as Alzheimer's disease and cerebrovascular disease, contribute to cognitive decline after hospitalization. The findings from this research will form the basis of an R01 grant application to the NIH before the end of the funding period.