Neuropathology for disrupted multiscale activity control in Alzheimer's disease

阿尔茨海默病多尺度活动控制中断的神经病理学

• 批准号: 9264449
• 负责人: Kun Hu
• 金额: $ 35.78万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264449
• 关键词: Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amygdaloid structure; Animals; Autopsy; Award; Behavior Control; Behavioral; Biology; Brain; Brain region; Caregivers; Cerebral cortex; Chronic; Circadian Rhythms; Clinical; Clinical Trials; Cognitive; Cohort Studies; Complex; Complication; Coupled; Cross-Sectional Studies; Databases; Dementia; Development; Disease; Disease Progression; Early Diagnosis; Early identification; Elderly; Epidemiology; Exhibits; Failure; Fractals; Functional disorder; Funding; Goals; Hippocampus (Brain); Hour; Human; Impaired cognition; Incidence; Individual; Israel; Laboratories; Lead; Long-Term Care; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Medical center; Memory; Methods; Modernization; Monitor; Motor; Motor Activity; Nerve Degeneration; Neurons; Nonlinear Dynamics; Outcome; Participant; Pathologic; Patients; Pattern; Periodicity; Physics; Physiological; Probability; Process; Property; Risk; Senile Plaques; Severity of illness; Sleep; Structure; System; Testing; Time; Tissues; age effect; base; circadian pacemaker; cognitive function; cognitive process; cost efficient; entorhinal cortex; follow up assessment; follow-up; multidisciplinary; neuroimaging; neuropathology; novel; predictive marker; predictive tools; prospective; public health relevance; relating to nervous system; suprachiasmatic nucleus; tool

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.

描述（由申请人提供）：阿尔茨海默病（AD）的早期诊断或AD风险的识别对于AD患者及其护理人员的更好结局非常重要。利用现代统计物理学和非线性动力学的新概念和方法，PI最近的研究表明，人类运动活动不仅在某些固定的时间尺度上表现出节律（例如，约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鲁棒分形波动。Te分形图案是独立的环境条件和持续时间从几秒钟到24小时，表明一个内在的多尺度活动控制。更重要的是PI和他的同事 显示多尺度活动控制（MAC）随着衰老而退化，并且在AD中进一步退化，并且退化的程度与淀粉样蛋白斑块（AD的标志）强烈相关，并且与昼夜节律性的传统测量相比，可以更好地预测昼夜节律功能障碍。这些结果提供了强有力的证据，证明MAC在生理上很重要，可能反映了运动活动控制系统的完整性和适应性。本项目的目的是测试MAC预测老年受试者认知能力下降和AD风险的能力。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）的独特数据库进行纵向研究-这是一项针对常见慢性衰老疾病的纵向流行病学临床病理队列研究，重点关注认知和运动功能下降以及AD风险。具体目标是：1）确定衰老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下降风险和阿尔茨海默病发病率的能力; 3）确定导致老年受试者多尺度活动控制中断的脑神经变性。实现这些目标将定义运动活动控制的退化的时间曲线及其与AD发展过程中大脑神经退行性变的关系。建议的MAC措施可以作为一个具有成本效益的，可靠的工具来预测AD的风险和监测疾病的进展。