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）：早期诊断阿尔茨海默氏病（AD）或鉴定AD风险对于AD和Thei护理人员的人来说，对更好的结果很重要。 PI使用源自现代统计物理学和非线性动力学的新颖概念和方法，最近的研究表明，人类运动活动不仅在某些固定时间尺度（例如，在〜24小时时在〜24小时时）表现出节奏，而且还表现出具有强大的分形波动，具有相似的时间结构和相似的时间尺度的统计特性。 TE分形模式与环境条件无关，并且从几秒钟到24小时持续存在，表明内在的多尺度活动控制。更重要的是，Pi和他的同事 表明多尺度活动控制（MAC）随着衰老而降解并进一步降解在AD中，并且降解程度与淀粉样蛋白斑块（AD的标志）密切相关，并且可以更好地预测与传统的昼夜节律性症状相比，与昼夜节律的昼夜节律性障碍相比。这些结果提供了有力的证据，表明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。该项目的GAL是测试MAC预测认知能力下降的能力和老年受试者的AD风险。为了实现这一目标，PI和他的团队提议使用1727名参与者（53-103岁）的独特数据库进行纵向研究，该数据集中在Rush Memory和Aging Project（MAP）中 - 一项纵向，流行病学的临床临床临床学会研究，对衰老的常见慢性条件的衰老持续性和MOTOTIC and Motion和Motion的强调降低了衰落的衰老常见慢性条件。具体目的是1）确定衰老和阿尔茨海默氏病对多尺度活动控制的纵向影响； 2）确定o多尺度活动控制能力的能力，以预测认知能力下降和阿尔茨海默氏病发病率的风险； 3）确定大脑中的神经退行性变化，导致较老受试者的多尺度活动控制。实现这些目标将定义运动活性控制中降解的时间概况及其与AD发育过程中大脑中神经变性的关系。提出的MAC措施可能是一种具有成本效益，可靠的工具，可预测AD的风险并监测疾病的发展。