Early Frailty Biomarkers: Patterns of Activity and Energy Expenditure

项目摘要/摘要 到2050年，美国人口将由8850万老年人口组成，他们的虚弱患病率将不断上升。 虚弱识别那些生理储备减少的人，并越来越多地被用来识别 再次住院、外科手术死亡率和卫生保健资源利用的高危人群。作为一名 作为一名接受过高级流行病学培训的老年病医生，我每天都在努力照顾复杂、虚弱的患者和 认识到需要准确的工具来量化脆弱性风险、趋势进展，以及更重要的是，指导 干预措施。自我报告的低体力活动参与是临床虚弱综合征的一部分，但自我 由于固有的偏见，报告未能充分识别那些在日常生活中表现出这一标准的人。 仅依靠自我报告可能会低估高危个人，并限制我们解决这一问题的能力 潜在的可修改组件。人们对运动和久坐行为的模式知之甚少 通过客观监测衡量的是与脆弱性相关的结果，以及这些措施如何 临床上应用于预测虚弱进展和指导个体化治疗。我的近期目标是 这项建议目的是研究活动的衡量标准如何与虚弱和衰老的结果以及 它们如何被用来为脆弱的干预提供信息。我假设独特的、可识别的模式 由活动监测器测量的活动将预测那些继续经历其脆弱程度下降的人。 和老化措施，并可用于量身定做治疗建议。为了检验这些假设， 提出了以下目标：目标1)描述非虚弱、先虚弱、 和使用活动监测的脆弱亚组，并将这些措施与5年脆弱和老龄化结果相关联； 目的2)在我独立的纵向脆弱研究中，将活动、久坐行为、坐立转换 和节奏来改变脆弱组件和一年后的老化结果；以及目标3)设计和中试测试a 脆弱干预工具，解决虚弱成年人的活动障碍，并为虚弱成年人量身定做活动目标 使用已识别的加速度计缺陷的个体。我将介绍来自国家社会服务中心的活动监测输出 生命、健康和老龄化项目数据(2010-2011年、2015-2016年)到5年的脆弱和老龄化结果。这就做 然后在我建立的临床队列(成功老龄化和虚弱评估诊所)中翻译这些发现 主要是使用活动监测和一年结果的虚弱前和虚弱的成年人。最后，我将使用 这些研究的结果与患者和专业利益相关者的意见相结合，以设计 适合虚弱老年人的可持续干预。这些拟议的研究将确定可修改的活动和 久坐行为可以使用活动监测来检测脆弱的风险因素，预测 进展，并指导治疗，从而促进我们对运动和久坐的作用的理解 虚弱的病理生理学和治疗中的行为。在颁奖期间，我将收到关键的 来自全国公认的老年研究人员琳达·韦特博士和威廉·戴尔博士的指导，以及 来自活动(艾米·卢克博士)、久坐行为(大卫·康罗伊博士)专家的补充指导 能量消耗(戴尔·斯科勒博士)、虚弱(杰里米·沃尔斯顿博士)、纵向调查和临床试验 分析(Masha Kocherginsky博士)和老年人的干预试验(Lee Lindquist博士)。我会拿到 在脆弱性、活动监测、统计学、临床试验设计和写作方面的高级培训。这项工作将为 为我的长期目标奠定基础，成为一名独立的临床研究员，在 虚弱的诊断和管理。

PROJECT SUMMARY / ABSTRACT By 2050, the American population will consist of 88.5 million older adults with a rising prevalence of frailty. Frailty identifies those with diminished physiologic reserve and is increasingly being used to recognize individuals at high risk of rehospitalization, surgical mortality, and health care resource utilization. As a geriatrician with advanced training in Epidemiology, I struggle daily to care for complex, frail patients and recognize the need for accurate tools to quantify frailty risk, trend progression, and to, importantly, guide interventions. Low self-reported physical activity participation is part of the clinical frailty syndrome, yet self- report fails to adequately identify those exhibiting this criterion in their daily lives due to inherent biases. Relying on self-report alone risks under-identifying high-risk individuals and limiting our ability to address this potentially modifiable component. Very little is known about how patterns of activity and sedentary behavior measured by objective monitoring are related to frailty-associated outcomes and how these measures can be applied clinically to predict frailty progression and to guide individualized treatment. My immediate goal and the objective of this proposal is to study how measures of (in)activity relate to frailty and aging outcomes and how they can be used to inform a frailty intervention. I hypothesize that unique, identifiable patterns of (in)activity as measured by activity monitors will predict those who go on to experience a decline in their frailty and aging measures and can be used to tailor treatment recommendations. To test these hypotheses, the following aims are proposed: Aim 1) Characterize activity and sedentary behavior among non-frail, pre-frail, and frail subgroups using activity monitors and relate these measures to 5-year frailty and aging outcomes; Aim 2) In my independent, longitudinal frailty study, relate activity, sedentary behavior, sit-to-stand transitions and cadence to change in frailty components and aging outcomes at 1-year; and Aim 3) Design and pilot test a frailty intervention tool that addresses activity barriers among frail adults and tailors activity targets for frail individuals using identified accelerometry deficits. I will relate activity monitor output from the National Social Life, Health and Aging Project data (2010-2011, 2015-2016) to frailty and aging outcomes at 5 years. I will then translate these findings in my established clinical cohort (Successful Aging and Frailty Evaluation clinic) of predominantly pre-frail and frail adults using activity monitoring and 1-year outcomes. Finally, I will use the findings from these studies in combination with patient and professional stakeholder input to design a sustainable intervention appropriate for frail elders. These proposed studies will identify modifiable activity and sedentary behaviors that can be measured using activity monitoring to detect frailty risk factors, predict progression, and guide treatment, and thus advance our understanding of the role of activity and sedentary behavior in the pathophysiology and treatment of frailty. During the award period, I will receive critical mentorship from nationally-recognized aging researchers, Drs. Linda Waite and William Dale, and supplementary guidance from experts in activity (Dr. Amy Luke), sedentary behavior (Dr. David Conroy), energy expenditure (Dr. Dale Schoeller), frailty (Dr. Jeremy Walston), longitudinal survey and clinical trial analysis (Dr. Masha Kocherginsky), and interventional trials in older adults (Dr. Lee Lindquist). I will obtain advanced training in frailty, activity monitoring, statistics, clinical trial design, and writing. This work will lay the foundation for my long-term goal of becoming an independent clinical investigator with expertise in the diagnosis and management of frailty.