Fractal motor activity regulation and the risk for Alzheimers disease in middle-to-old aged adults

项目摘要/摘要 阿尔茨海默病(AD)的临床表现，如记忆力丧失和认知障碍 主要发生在65岁的人群中。但据信，这种疾病在十多年的时间里一直在悄悄地发展 在其临床表现之前，疾病进程最早开始于45岁左右。这 阿尔茨海默病的临床前阶段将为有效的治疗干预提供关键的机会。因此，早些时候 确定有AD风险的个人对于这些人更好的健康结局是重要的，并且 他们的照顾者。本课题的目标是确定人体生理过程中的分形调控能力。 波动预测中老年AD的风险。许多生理波动，包括 心率和运动活动的波动呈现出分形图案，即波动的图案非常 在不同的时间尺度上相似。大量研究表明，分形规律对 在可塑性和适应性方面的生理优势，例如减少心脏和心脏的分形性 随着年龄的增长和病理条件下的运动活动调节，最重要的是，通过预测性 减少心脏分形性调节对降低存活率的价值。Pi的团队是第一批展示 退化的分形规则与阿尔茨海默病(AD)之间的机制联系。他们发现这种分形体 运动活动调节(FMAR)随着年龄的增长和AD的发生而降解，而且这种降解是强烈的 与认知能力下降有关。基于这些初步数据，该提案旨在测试 FMAR改变可预测中老年AD发病。为此，Pi和他的团队提议 研究英国生物库(http://www.ukbiobank.ac.uk))的现有数据库，其中约500,000名参与者年龄 在2006-2010年招募了40到69岁的人，并同意对他们的健康进行跟踪。具体目标 1)确定年龄和AD的遗传风险对中老年人群FMAR的影响；2) 确定中老年人群中FMAR与认知和AD事件的关系；3) 确定中老年人群神经解剖学改变对FMAR的影响。解决目标问题 将提供从中年到老年的分形规则变化的第一个正式评估， 潜在的神经解剖学变化，以及它在早期或临床前阶段预测AD风险的能力。 这些结果将使我们更好地理解健康和健康的 阿尔茨海默病的病理性老化，应为改善AD的诊断和治疗提供有用的指导 与AD相关的症状。

Project Summary/Abstract Clinical manifestations of Alzheimer's disease (AD) such as memory loss and cognition impairment occur mostly in people aged 65 years. But the disease is believed to progresses silently for more than a decade before its clinical manifestations such that the disease process starts as early as in the middle of 40s. This preclinical phase of AD would provide a critical opportunity for effective therapeutic interventions. Thus, earlier identification of the individuals at the risk for AD is important for better healthy outcomes of these people and their caregivers. The goal of this project is to determine the ability of fractal regulation in physiological fluctuations to predict the risk of AD in middle to old aged people. Many physiological fluctuations including heart rate and motor activity fluctuations display fractal patterns, i.e., the patterns of fluctuations are very similar at different time scales. Numerous studies indicate that fractal regulation imparts considerable physiological advantage in terms of plasticity and adaptability, as exemplified by reduced fractal cardiac and motor activity regulations with aging and under pathological conditions, and most importantly, by the predictive value of reduced fractal cardiac regulation for decreased survival. PI's group is one of the first to show a mechanistic link between degraded fractal regulation and Alzheimer's disease (AD). They found that fractal motor activity regulation (FMAR) is degraded with aging and in AD, and that the degradation is strongly associated with cognitive decline. Based on these preliminary data, the proposal is designed to test whether FMAR alterations predict incident AD in middle to old aged people. To this end, PI and his team propose to study the existing database of UK Biobank (http://www.ukbiobank.ac.uk) in which ~500,000 participants aged between 40-69 years were recruited in 2006-2010 and agreed to have their health followed. The specific aims are 1) to determine the effects of age and genetic risk for AD on FMAR in middle-to-old aged adults; 2) to determine the associations of FMAR with cognition and incident AD in middle-to-old aged adults; and 3) to determine the effects of neuroanatomical changes on FMAR in middle-to-old aged adults. Addressing the aims will provide a first formal assessment of the alterations of fractal regulation from middle to old ages, the underlying neuroanatomical changes, and its ability to predict the risk of AD at early or preclinical stages. These results will lead to a much better understanding of the complex biology and physiology of healthy and pathologic aging in AD, which ought to provide useful guidance for improved diagnosis and treatment of AD or AD-related symptoms.