Longitudinal Hemodynamic and Vascular Changes associated with Frailty

 描述(申请人提供)：到2030年，7200万美国人将超过65岁，其中近900万人将超过85岁。脆弱是一种公认的 一种重要的老年综合征，导致多个相互关联的系统的衰退，这些系统在应对压力因素(如急性医疗保健事件)时会导致储备的丧失。虚弱综合征与住院、住院、发病率和死亡率密切相关。由于与虚弱相关的功能健康状况下降而导致的残疾正在并将成为临床、经济和社会层面上日益沉重的负担。身体虚弱、心血管疾病(CVD)和认知障碍之间存在着复杂的相互作用。患有心血管疾病的个体有很高的虚弱患病率，患有心血管疾病的虚弱成年人的预后明显比单独患有心血管疾病的个体更差。身体虚弱是认知障碍的风险因素，与虚弱相关的血管风险因素也与阿尔茨海默病的发病率和患病率增加有关。对心血管疾病、认知障碍和身体虚弱之间的相互作用的了解主要停留在流行病学层面，限制了理解机制和制定干预目标的能力。这项拟议的研究旨在确定与虚弱综合征纵向进展相关的特定血流动力学和血管变化。在目标1中，我将把心脏MRI评估的血流动力学异常(即反映心室-动脉偶联变化的动脉血管僵硬和左心室充盈受损)与36个月来脆弱的纵向进展(通过综合脆弱评分的变化来衡量)联系起来。在目标2中，我将把血流动力学异常与一个被提出的脆弱中间标志物(通过定量MRI大腿肌分析测量的骨骼肌质量的变化)从基线到36个月的纵向进展联系起来。在目标3中，我将在36个月的随访期内将血流动力学异常(由心脏MRI评估)和虚弱状态(作为效应调节剂)与神经心理功能的纵向变化联系起来。我认为，这项研究提供了一种独特的方法创新，将在生理和机制层面上显著推动该领域的发展。这项工作的集体成果将是 有可能开展一项旨在降低心血管因素的脆弱性的干预性研究。

 DESCRIPTION (provided by applicant): Abstract By 2030, 72 million Americans will be over the age of 65 and of those almost 9 million will be over the age of 85. Frailty is a recognized and important geriatric syndrome that results in a decline across multiple interrelated systems that confer a loss of reserve in response to stressors, such as acute health care events. The frailty syndrome is highly associated with hospitalization, institutionalization, morbidity and mortality. Disability due to declining functional health status associated with frailty is and will become an increasing burden at a clinical, financial, and social level. A complex interaction exists between physical frailty, cardiovascular disease (CVD), and cognitive impairment. Individuals with CVD have a high prevalence of frailty, and frail adults with CVD have significantly worse outcomes than individuals with CVD alone. Physical frailty is a risk factor for cognitive impairment, and frailty-related vascular risk factors are also associated with increased Alzheimer's disease incidence and prevalence. An understanding of the interaction between cardiovascular disease, cognitive impairment and physical frailty has remained predominantly at an epidemiological level, limiting the ability to understand mechanisms and develop targets for intervention. The proposed research looks to determine specific hemodynamic and vascular changes associated with the longitudinal progression of the frailty syndrome. In Aim 1, I will relate hemodynamic abnormalities assessed by cardiac MRI (i.e., arterial vascular stiffness and impaired left ventricular filling reflective of changes in ventricular-arterial coupling) to the longitudinal progression of frailty (as measured by change in composite frailty score) over 36 months. In Aim 2, I will relate hemodynamic abnormalities to the longitudinal progression of a proposed intermediate marker of frailty (change in skeletal muscle quality as measured by quantitative MRI thigh muscle analysis) from baseline to 36 months. In Aim 3, I will relate hemodynamic abnormalities (as assessed by cardiac MRI) and frailty status (as an effect modifier) to longitudinal change in neuropsychological function over the 36-month follow-up period. I propose that this research offers a unique methodological innovation that will significantly advance the field on a physiological and mechanistic level. The collective result of this work will be the possible development of an interventional study targeted toward reducing frailty that focuses on cardiovascular factors.