Testing the Validity of a Construct of Geriatric Frailty

描述（由申请人提供）：研究人员寻求对探索性/发展性研究项目的支持，该项目将为老年虚弱综合征的复杂生物学和病理生理学提供新的见解。虚弱是一个非常重要的老年医学临床主题，但研究一直受到缺乏一个商定的定义虚弱。对脆弱性的有效操作定义可以大大加强对脆弱性的原因和后果的研究。尽管在已发表的文献中提出了许多关于“虚弱”的定义，但该术语通常在临床上作为一个全球性概念用于描述一种常见于高龄者的状况，即力量和耐力受损，对压力源的脆弱性增加，以及发病、残疾和死亡的风险增加。在2001年的一篇具有里程碑意义的论文中，Fried及其同事使用了心血管健康研究（CHS）的数据，并将虚弱的表型定义为包括以下3种或更多种：无意的体重减轻，虚弱，疲惫，步态缓慢和低体力活动水平。使用该定义发现虚弱的老年人出现不良健康结局的风险增加，与其社会人口学特征、医学合并症和残疾程度无关。这个定义提供了一个有用的操作起点，在追求对理解和最终预防和治疗脆弱，但其结构效度的经验支持是不完整的。这个多学科的研究小组建议使用麦克阿瑟成功老龄化研究（MSSA）中收集的数据，一项对1189名老年人的纵向队列研究：1）使用结构方程模型来检验所选CHS标准的结构效度;（二）从经验上探索CHS对虚弱的定义是否可以通过扩展定义以包括已经假设的不同标准来增强作为虚弱的一部分（如认知障碍）; 3）测试老年虚弱是否由具有不同特征模式的相关亚表型（身体、认知、行为和炎症）代表;和5）检查神经内分泌、心理社会和社会人口特征在预测虚弱中的潜在作用。MSSA提供了一个非凡的机会来获得对老年虚弱综合征的新见解，因为这个丰富的数据集包括CHS中用于定义虚弱的所有5个标准的测量，它还包括残疾和合并症的严格测量，炎症的血清标志物，神经内分泌失调的尿液标志物，认知功能的详细测量，长期住院和死亡率数据，以及许多可能与虚弱相关的心理社会结构的测量。总之，这项探索性研究提供了一个独特的和具有成本效益的手段，打破了我们对老年综合征的理解。

DESCRIPTION (provided by applicant): The investigators seek support for an exploratory/developmental research project that will offer new insights into the complex biology and pathophysiology underlying the geriatric syndrome of frailty. Frailty is a topic of great clinical importance to geriatric medicine, but research has been hampered by a lack of an agreed-upon definition of frailty. Valid operational definitions of frailty could greatly enhance research on the causes and consequences of frailty. Though numerous definitions of "frailty" have been proposed in the published literature, the term has usually been used clinically as a global concept to describe a condition, common in the very old, of impaired strength and endurance, increased vulnerability to stressors, and increased risk for morbidity, disability and mortality. In a landmark paper in 2001, Fried and colleagues used data from the Cardiovascular Health Study (CHS) and defined a phenotype of frailty to include 3 or more of the following: unintentional weight loss, weakness, exhaustion, slow gait, and low physical activity level. Older adults found to be frail using this definition were at increased risk for adverse health outcomes, independent of their sociodemographic characteristics, medical comorbidities, and level of disability. This definition provides a useful operational starting point in the quest towards understanding and ultimately preventing and treating frailty, but empiric support of its construct validity is incomplete. This multidisciplinary team proposes to use data previously-collected in the MacArthur Study of Successful Aging (MSSA), a longitudinal cohort study of 1189 older adults, to: 1) use structural equation modeling to test the construct validity of the selected CHS criteria; 2) empirically explore whether the CHS definition of frailty could be enhanced by expanding the definition to include differing criteria that have been hypothesized to be part of frailty (such as cognitive impairment); 3) test whether geriatric frailty is represented by correlated sub-phenotypes (physical, cognitive, behavioral and inflammatory) with different characteristic patterns; and 5) examine the potential role of neuroendocrine, psychosocial and sociodemographic characteristics in predicting frailty. The MSSA offers an extraordinary opportunity to gain new insights into the geriatric syndrome of frailty because this rich dataset includes measures of all 5 of the criteria used in CHS to define frailty, and it also includes rigorous measures of disability and comorbidity, serum markers of inflammation, urine markers of neuroendocrine dysregulation, detailed measures of cognitive function, long-term hospitalization and mortality data, as well as measures of many psychosocial constructs that may be associated with frailty. In summary, this exploratory investigation offers a unique and cost-effective means to break new ground in our understanding of the geriatric syndrome of frailty.