Nonlinear Dynamics of Frailty in Aging

在过去的20年里，我们的研究团队使用非线性动力学和分形分析工具进行了合作，研究小组已经表明，衰老和疾病与各种生理系统动力学中复杂性的丧失有关。我们已经提出，这种复杂性的丧失可能会导致适应能力的降低、功能的下降和脆弱。因此，可以量化生理系统的动力学及其相互作用的非线性数学技术可能有助于描述脆弱综合征的特征。因此，我们的目标是：1)在70岁及以上的具有代表性的老年人群体中，横断面确定包括心血管(心跳间期和血压(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)控制系统在内的多个生理系统的动态变化是否存在脆弱与复杂性丧失之间的关系。我们还将通过检查相互作用系统(例如，心脏和呼吸，或全身血压和大脑BFV)的动态测量之间的相关性、一致性、相位和传递函数增益，来确定这些系统之间的相互作用是否会在虚弱的老年人中退化。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在这些系统上的常见生理应激的能力受损有关。我们将具体研究：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)安静站立的压力轨迹与其对叠加认知任务的反应之间的关系。3)在同一人群的两年纵向随访期内，确定这些生理系统在基线时动力学的复杂性降低，或这些系统的复杂性随着时间的推移而降低，是否预示着随后脆弱的发展，其组成部分症状，和/或身体和认知功能下降的其他衡量标准。为了实现这些目标，我们将处理和分析从一个具有良好特征的、前瞻性跟踪的、以人口为基础的样本中收集的生理数据，这些样本包括800名70岁以上的老年人，他们参加了正在进行的NIA资助的项目赠款(HRCA/哈佛研究疗养院，P01-AG004390)。研究团队在临床老年学研究、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出色资源，将有助于确保项目的成功。

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.