Nonlinear Dynamics of Frailty in Aging

在过去20年的合作工作中，我们的研究团队使用非线性动力学和分形分析工具，表明衰老和疾病与各种生理系统动力学复杂性的丧失有关。我们已经提出，这种复杂性的丧失会导致适应能力的降低、功能的衰退和脆弱。非线性数学技术可以量化生理系统的动力学和它们之间的相互作用，因此，可能有助于表征虚弱综合征。因此，我们的目标是：1)在具有代表性的70岁及以上老年人人群中，横断面确定“脆弱”与多个生理系统动力学复杂性丧失之间是否存在关系，包括心血管（搏动间隔（RR）和血压（BP））、脑血管（脑血流速度（BFV））、呼吸（间歇）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（例如，心脏和呼吸，或全身血压和脑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体弱的老年人中退化。2)确定心脑血管和/或平衡动力学复杂性的丧失是否与施加在这些系统上的常见生理压力的适应能力受损有关。我们将特别研究：a)静息血压、RR间隔或脑血流动力学与他们对姿势变化的反应之间的关系，以及b)安静站立的压力中心轨迹与他们对叠加认知任务的反应之间的关系。3)在同一人群中进行为期两年的纵向随访，以确定这些生理系统在基线时动态复杂性的降低，或随着时间的推移这些系统复杂性的丧失，是否可预测随后的虚弱发展，其组成症状，和/或其他身体和认知功能下降的指标。为了实现这些目标，我们将处理和分析生理数据，这些数据来自于800名70岁以上的老年人，这些老年人正在参加nia资助的项目项目拨款（HRCA/哈佛研究养老院，P01-AG004390），这些数据具有良好的特征，具有前瞻性，基于人群的样本。研究团队在老年临床研究、生理学、动态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.