SENILE CHANGES IN CIRCADIAN RHYTHMS AND BEHAVIOR

睡眠障碍和其他行为障碍是常见的投诉 阿尔茨海默病（AD）患者及其家属， 往往导致制度化。 以前的证据 研究表明，这些临床问题可能部分是由于 与年龄和疾病有关的障碍，在一个或多个组成部分， 人体生理节奏计时系统 我们研究的长期目标是双重和互补的： 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， 昼夜节律计时系统; 2. 为了阐明的机制，结构组成部分的 昼夜节律计时系统影响行为，使用病理条件 (AD)作为自然的实验。 这项研究的具体目标是： 1. 采用恒定的常规方案来确定振幅， AD中内源性昼夜节律起搏点的相位，不受那些掩蔽 自然条件下的影响; 2. 评估AD中振幅和相位变化之间的关系 以及睡眠碎片和躁动行为的客观测量; 3. 为了建立振幅和相位之间的关系， 内源性昼夜节律起搏器和大小，细胞结构和 视交叉上核（SCN）的神经病理学， 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研究。 评估，然后是死后神经病理学研究，90 仔细诊断AD患者。 18名对照人群 将在相同的条件下研究健康的老年受试者。 睡眠和躁动的临床测量将通过直接， 由经过培训的评定者进行72小时的连续行为观察。 然后将在常规检查中对受试者进行评价 议定书 确定其内源性昼夜节律的幅度和相位 起搏器，独立于睡眠，活动， 姿势、饮食和灯光。 将进行统计学比较， 对照组和行为观察数据。 患者将 纵向跟踪直至尸检，并进行神经病理学检查 将进行检查以确定痴呆诊断。 将使用形态学和免疫细胞化学技术来确定 SCN的胶质/神经元比率和加压素细胞构成。 SCN变性的这些指标之间的统计相关性， 患有病理学证实的AD的患者， 将测试内源性昼夜节律起搏器。

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.