Early Frailty Biomarkers: Patterns of Activity and Energy Expenditure

 描述（由申请人提供）：到2050年，美国人口将由8850万老年人组成，虚弱的患病率不断上升。虚弱是指那些生理储备减少的人，并且越来越多地用于识别再住院、手术死亡率和医疗资源利用率高的个体。作为一名老年病学家， 在流行病学的高级培训，我每天都在努力照顾复杂，虚弱的病人，并认识到需要准确的工具来量化虚弱风险，趋势进展，并重要的是，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，然而由于固有的偏见，自我报告未能充分识别在日常生活中表现出这种标准的人。仅仅依靠自我报告可能会低估高风险个体的识别能力，并限制我们解决这一潜在的可修改部分的能力。关于通过客观监测测量的活动和久坐行为模式如何与虚弱相关的结果相关，以及这些措施如何在临床上应用于预测虚弱进展并指导个体化治疗，我们知之甚少。我的近期目标和本提案的目标是研究活动（不活动）的措施如何与虚弱和衰老结果相关，以及如何使用它们来为虚弱干预提供信息。我假设，活动监测仪测量的独特的、可识别的活动模式将预测那些继续经历虚弱和衰老指标下降的人，并可用于定制治疗建议。为了验证这些假设，提出了以下目标：目标1）使用活动监测器表征非虚弱，虚弱前和虚弱亚组中的活动和久坐行为，并将这些措施与5年的虚弱和衰老结果相关联;目的2）在我的独立的纵向脆弱性研究中，相关活动，久坐行为，1年时，从坐到站的转换和节奏，以改变虚弱组件和老化结局;（3）设计并试点测试一种虚弱干预工具，以解决虚弱成年人的活动障碍并为虚弱成年人量身定制活动目标使用已识别的加速度计缺陷的个体。 将国家社会生活、健康和老龄化项目数据（2010-2011年，2015-2016年）的活动监测输出与5年时的虚弱和老龄化结局相关联。然后，我将在我建立的临床队列（成功衰老和虚弱评估诊所）中使用活动监测和1年结果将这些发现转化为主要的虚弱前和虚弱成人。最后，我将利用这些研究的结果，结合病人和专业持份者的意见，设计一个适合体弱长者的可持续干预措施。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虚弱风险因素，预测进展并指导治疗，从而促进我们对活动和久坐行为在虚弱的病理生理学和治疗中的作用的理解。在获奖期间，我将获得全国知名的老龄化研究人员琳达·韦特博士和威廉·戴尔博士的重要指导，以及活动专家的补充指导（艾米·卢克博士），久坐行为（大卫康罗伊博士），能量消耗（Dale Schoeller博士），虚弱（Jeremy Walston博士）、纵向调查和临床试验分析（Masha Kocherginsky博士）以及老年人干预性试验（Le Lindquist博士）。我将获得虚弱，活动监测，统计，临床试验设计和写作方面的高级培训。这项工作将为我的长期目标奠定基础，成为一名独立的临床研究者，在诊断和管理脆弱方面具有专业知识。

 DESCRIPTION (provided by applicant): 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 critrion 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. 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. Le Lindquist). I will obtain advanced training in frailty, activity monitoring, statistics, clinical tial 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.