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 研究小组已经表明，衰老和疾病与各种动力学的复杂性丧失有关。 生理系统我们已经提出，这种复杂性的丧失会导致适应能力的降低， 衰落和虚弱非线性数学技术，可以量化生理系统的动力学及其 因此，相互作用可能有助于描述虚弱综合征的特征。因此，我们的目标是：1）确定交叉- 在70岁及以上的代表性老年人口中， 在多个生理系统（包括心血管系统）的动力学中， （心跳（RR）间期和血压（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。我们还将确定 通过检查这些系统之间的相互作用的相关性，一致性，相位， 以及交互系统的动态测量之间的传递函数增益（例如，心脏和呼吸系统，或 全身BP和脑BFV）。2)以确定是否有复杂的心血管，脑血管， 和/或平衡动力学，与适应施加于 这些系统。我们将具体研究以下因素之间的关系：a）静息血压、RR间期或脑血流量 流动动力学及其对姿势变化的响应，以及B）安静站立的压力中心轨迹及其 对叠加认知任务的反应。3)为了确定，在两年的随访期内， 相同的人群，无论是在基线时这些生理系统的动力学复杂性降低，还是在基线时这些生理系统的功能丧失， 随着时间的推移，这些系统的复杂性可以预测随后的虚弱发展，其组成症状， 和/或身体和认知功能下降的其它测量。为了实现这些目标，我们将处理和分析 生理数据是从一个良好表征的，前瞻性的，基于人群的样本中收集的， 800名70岁以上的老年人，他们正在参加一个正在进行的NIA资助的计划项目赠款（ HRCA/哈佛研究疗养院，P01-AG 004390）。老年医学临床研究团队的经验 研究，生理学，动力系统和生物统计学，以及希伯来语的杰出资源 康复中心和哈佛医学院将帮助确保该项目的成功。

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 complexitycan 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 cross- sectionally 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.