SENILE CHANGES IN CIRCADIAN RHYTHMS AND BEHAVIOR

老年昼夜节律和行为的变化

• 批准号: 2050727
• 负责人: ANDREW SATLIN
• 金额: $ 25.17万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2050727
• 关键词: Alzheimer's disease; aging; behavior disorders; behavior test; body physical activity; body temperature; circadian rhythms; glia; histopathology; human old age (65+); human subject; immunocytochemistry; longitudinal human study; neural degeneration; neurons; postmortem; sleep disorders; statistics /biometry; suprachiasmatic nucleus; vasopressins

Sleep disorders and other behavioral disturbances are common complaints among patients with Alzheimer's disease (AD) and their families, and frequently result in institutionalization. Evidence from previous investigations suggests that these clinical problems may be due in part to age- and disease-related disturbances in one or more components of the human circadian timing system. The long-term goals of our research are two-fold and complementary: 1. To determine the pathophysiology of sleep and behavioral disturbances in AD as these related to abnormalities of structure and function in the circadian timing system; 2. To elucidate the mechanisms by which structural components of the circadian timing system affect behavior, using a pathological condition (AD) as an experiment of nature. The specific aims of this research are: 1. To employ a constant routine protocol to determine the amplitude and phase of the endogenous circadian pacemaker in AD, free of those masking influences present under natural conditions; 2. To assess the relationship between amplitude and phase changes in AD and objective measures of sleep fragmentation and agitated behavior; 3. To establish the relationship between the amplitude and phase of the endogenous circadian pacemaker and the size, cellularity and neuropathology of the suprachiasmatic nucleus (SCN), the putative anatomic location of that pacemaker. To accomplish these aims, we will conduct longitudinal clinical evaluations, followed by post-mortem neuropathological studies, of 90 carefully diagnosed AD patients. A control population of 18 matched healthy elderly subjects will be studied under identical conditions. Clinical measures of sleep and agitation will be obtained by direct, continuous behavioral observation by trained raters for 72 hours. Subjects then will be evaluated during a constant routine protocol to determine the amplitude and phase of their endogenous circadian pacemaker, independent of the masking influences of sleep, activity, posture, meals and lighting. Statistical comparisons will be made with controls, and with the behavioral observation data. Patients will be followed longitudinally until autopsy, and a neuropathological examination will be performed to establish the dementia diagnosis. Morphometric and immunocytochemical techniques will be used to determine the glial/neuron ratio and vasopressin cellularity of the SCN. Statistical correlations between these indices of SCN degeneration in patients with pathologically-confirmed AD and the amplitude and phase of the endogenous circadian pacemaker will be tested.

睡眠障碍和其他行为障碍是常见的投诉 在阿尔茨海默氏病（AD）及其家人的患者中 经常导致制度化。 以前的证据 调查表明，这些临床问题可能部分是由于 在一个或多个组成部分中与年龄和疾病相关的障碍 人类的昼夜节律定时系统。 我们研究的长期目标是两个方面和互补的： 1。确定睡眠和行为障碍的病理生理学 在AD中，这些与结构和功能异常有关 昼夜节律系统； 2。阐明结构成分的机制 昼夜节律系统使用病理状况会影响行为 （AD）作为自然的实验。 这项研究的具体目的是： 1。采用恒定常规协议来确定幅度和 AD中的内源性昼夜节奏起搏器的阶段，没有那些掩盖 在自然条件下的影响； 2。评估AD的幅度与相变之间的关系 和睡眠破碎和搅动行为的客观度量； 3。建立幅度和相位之间的关系 内源性昼夜节奏起搏器以及大小，细胞性和 假定核（SCN）的神经病理学，推定 该起搏器的解剖位置。 为了实现这些目标，我们将进行纵向临床 评估，随后是验尸后神经病理学研究，为90 精心诊断的AD患者。 对照人群18匹配 健康的老年受试者将在相同的条件下进行研究。 睡眠和搅动的临床指标将通过直接获得 训练有素的评估者连续观察72小时。 然后，将在恒定的例程协议期间评估受试者 确定其内源昼夜节律的幅度和相位 起搏器，独立于睡眠，活动的影响， 姿势，饭菜和照明。 统计比较将与 控制和行为观察数据。 患者会 纵向直到尸检和神经病理学 检查将进行检查以建立痴呆症诊断。 形态计量和免疫细胞化学技术将用于确定 SCN的神经胶质/神经元比和加压素细胞。 这些SCN变性指标之间的统计相关性 患有病理确认的AD的患者以及 内源性昼夜节奏起搏器将进行测试。