Nonlinear Dynamics of Frailty in Aging

在过去20年的合作工作中，使用非线性动力学和分形分析的工具，我们的研究团队已经表明，衰老和疾病与各种生理系统动力学的复杂性丧失有关。我们已经提出，这种复杂性的丧失可能导致适应能力降低，功能衰退和脆弱。非线性数学技术，可以量化的生理系统及其相互作用的动力学，因此，可能有助于表征虚弱综合征。因此，我们的目标是：1）在70岁及以上的老年人的代表性人群中，确定“虚弱”与多个生理系统（包括心血管系统）的动力学复杂性丧失之间是否存在关系。（心搏间期（RR）和血压（BP）），脑血管（脑血流速度（BFV））、呼吸（呼吸间隔）和平衡（压力中心轨迹）控制系统。我们还将通过检查相互作用系统的动态测量之间的相关性、一致性、相位和传递函数增益（例如，心脏和呼吸，或全身BP和脑BFV）。2)确定心血管、脑血管和/或平衡动力学复杂性的丧失是否与适应施加于这些系统的常见生理应激的能力受损相关。我们将具体研究以下两种情况之间的关系：a）静息BP、RR间期或脑血流动力学及其对姿势变化的反应，以及B）安静站立压力中心轨迹及其对叠加认知任务的反应。3)在相同人群中纵向随访2年，确定基线时这些生理系统的动力学复杂性降低或这些系统随时间推移复杂性丧失是否可预测随后发生的虚弱、其组成症状和/或身体和认知功能下降的其他指标。为了实现这些目标，我们将处理和分析生理数据，这些数据是从800名70岁以上的老年人中收集的，这些老年人参加了一项正在进行的NIA资助的项目资助（HRCA/哈佛研究护理之家，P01-AG 004390）。研究团队在临床老年医学研究、生理学、动力系统和生物统计学方面的经验，以及希伯来康复中心和哈佛医学院的优秀资源，将有助于确保该项目的成功。

Over the past 2 decades of collaborative work using the tools of nonlinear dynamics and fractal analysis, our research team has shown that aging and disease are associated with a loss of complexity in the dynamics of a variety of physiologic systems. We have proposed that this loss of complexity can lead to reduced adaptive capacity, functional decline, and frailty. Nonlinear mathematical techniques that can quantify the dynamics of physiologic systems and their interactions may, therefore, help characterize the syndrome of frailty. Accordingly, we aim: 1) To determine crosssectionally in a representative population of elderly people aged 70 years and over, whether there is a relationship between "frailty" and loss of complexity in the dynamics of multiple physiologic systems, including cardiovascular (interbeat (RR) intervals and blood pressure (BP)), cerebrovascular (cerebral blood flow velocity (BFV)), respiratory (interbreath intervals), and balance (center-of-pressure trajectories) control systems. We will also determine whether interactions between these systems degrade in frail elderly individuals by examining the correlations, coherence, phase, and transfer function gains between the dynamic measures of interacting systems (e.g., cardiac and respiratory, or systemic BP and cerebral BFV). 2) To determine whether a loss of complexity in cardiovascular, cerebrovascular, and/or balance dynamics, is associated with an impaired ability to adapt to common physiologic stresses imposed on these systems. We will examine specifically the relationships between: a) resting BP, RR intervals, or cerebral blood flow dynamics and their responses to posture change, and b) quiet standing center-of pressure trajectories and their response to a superimposed cognitive task. 3) To determine, longitudinally over a two-year follow-up period in the same population, whether reduced complexity in the dynamics of these physiologic systems at baseline, or loss of complexity in these systems over time, is predictive of the subsequent development of frailty, its component symptoms, and/or other measures of physical and cognitive functional decline. To achieve these aims we will process and analyze physiologic data that are being gathered from a well-characterized, prospectively followed, population-based sample of 800 elderly people over age 70 who are participating in an ongoing NIA-funded Program Project Grant (the HRCA/Harvard Research Nursing Home, P01-AG004390). The experience of the research team in clinical geriatric research, physiology, dynamic systems, and biostatistics, as well as the outstanding resources of the Hebrew Rehabilitation Center and Harvard Medical School will help assure the project's success.