Neuropathology for disrupted multiscale activity control in Alzheimer's disease

描述(由申请人提供)：早期诊断阿尔茨海默病(AD)或确定AD的风险对于AD患者及其照顾者的更好结果非常重要。利用现代统计物理学和非线性动力学的新概念和新方法，Pi最近的研究表明，人类运动活动不仅在一定的固定时间尺度上表现出节律(例如~24小时的昼夜节律)，而且在不同的时间尺度上具有相似的时间结构和统计特性的稳健的分形波动。TE分形图与环境条件无关，从几秒钟持续到24小时，表明内在的多尺度活动控制。更重要的是，派和他的同事们 研究表明，多尺度活动控制(MAC)随着年龄的增长而退化，并在AD中进一步退化，并且退化的程度与淀粉样斑块(AD的一个特征)密切相关，与传统的昼夜节律性指标相比，多尺度活动控制(MAC)可以更好地预测昼夜节律障碍。这些结果提供了强有力的证据，表明MAC在生理上是重要的，可能反映了运动活动控制系统的完整性和适应性。本项目的GAL是为了测试MAC对老年受试者认知功能减退和AD风险的预测能力。为了实现这一目标，Pi和他的团队建议使用Rush Memory and Aging Project(MAP)中收集的1727名参与者(53-103岁)的独特数据库进行一项纵向研究。MAP是一项关于常见慢性老龄化状况的纵向、流行病学临床-病理队列研究，重点是认知和运动功能下降以及AD的风险。具体目标是1)确定老龄化和阿尔茨海默病对多尺度活动控制的纵向影响；2)前瞻性地确定多尺度活动控制预测认知能力下降和阿尔茨海默病发病率的能力；3)确定导致老年人多尺度活动控制中断的大脑神经变性。实现这些目标将确定AD发展过程中运动活动控制退化的时间分布及其与大脑神经退行性变的关系。拟议的MAC措施可能成为预测AD风险和监测疾病进展的一种经济高效、可靠的工具。

DESCRIPTION (provided by applicant): Early diagnosis of Alzheimer's disease (AD) or identification of the risk for AD is important for better outcomes for individuals with AD and thei caregivers. Using novel concepts and methods derived from modern statistical physics and nonlinear dynamics, PI's recent studies show that human motor activity exhibits not only rhythms at certain fixed time scales (e.g. circadian rhythms at ~24 hours), but also robust fractal fluctuations with similar temporal structure and statistical properties at different time scales. Te fractal patterns are independent of environmental conditions and persist from seconds up to 24 hours, indicating an intrinsic multiscale activity control. More importantly, PI and his colleagues show that multiscale activity control (MAC) is degraded with aging and further degraded in AD, and that the degree of the degradation is strongly associated with amyloid plaques (a hallmark of AD), and can better predict circadian dysfunction as compared to traditional measures of circadian rhythmicity. These results provide strong evidence that MAC is physiologically important, likely reflecting integrity and adaptability of the motor activity control system. The gal of this project is to test the ability of MAC to predict cognitive decline and the risk for AD in elderly subjects. To achieve this goal, PI and his team propose to perform a longitudinal study using the unique database of 1727 participants (53-103 years old), collected in the Rush Memory and Aging Project (MAP) - a longitudinal, epidemiologic clinical-pathologic cohort study of common chronic conditions of aging with an emphasis on decline in cognitive and motor function and risk of AD. The specific aims are 1) to determine the longitudinal effects of aging and Alzheimer's disease on multiscale activity control; 2) to determine prospectively the ability o multiscale activity control to predict the risk of cognitive decline and Alzheimer's disease incidence; 3) to identify neurodegeneration in brain that contribute to disrupted multiscale activity control in older subjects. Achieving these aims will define the temporal profile of the degradation in motor activity control and its relationship with neurodegeneration in the brain during the development of AD. The proposed MAC measures may serve as a cost-efficient, reliable tool to predict the risk of AD and to monitor the progression of the disease.