SENILE CHANGES IN CIRCADIAN RHYTHMS AND BEHAVIOR

睡眠障碍和其他行为障碍是常见的主诉 在阿尔茨海默病(AD)患者及其家人中， 经常导致制度化。以前的证据 调查表明，这些临床问题可能是部分原因。 与年龄和疾病相关的障碍有关的一个或多个组成部分 人类昼夜节律计时系统。 我们研究的长期目标是双重和相辅相成的： 1.确定睡眠和行为障碍的病理生理学 在AD中，这些与脑结构和功能的异常有关 昼夜节律计时系统； 2.阐明人参皂甙的结构成分的作用机制 昼夜节律系统影响行为，使用一种病理状态 (公元)作为一种自然实验。 这项研究的具体目的是： 1.采用恒定的常规方案来确定幅度和 阿尔茨海默病患者的内源性昼夜节律起搏器的时相，没有这些掩蔽 自然条件下存在的影响； 2.评价阿尔茨海默病的幅度和相位变化之间的关系 客观测量睡眠碎片化和躁动行为； 3.建立信号的幅度和相位之间的关系 内源性昼夜节律起搏器的大小、细胞密度和 视交叉上核的神经病理学 起搏器的解剖位置。 为了达到这些目标，我们将进行纵向临床 评估，随后进行死后神经病理学研究，共90人 仔细诊断AD患者。18个配对的对照种群 健康的老年受试者将在相同的条件下进行研究。 睡眠和躁动的临床测量将通过直接、 由训练有素的评分员连续观察72小时。 然后，受试者将在固定的常规方案期间进行评估，以 确定它们的内源性昼夜节律的幅度和相位 起搏器，不受睡眠、活动、 姿势、用餐和灯光。统计上的比较将与 对照，并与行为观察数据进行比较。病人将会是 纵向追踪，直到尸检，和神经病理 将进行检查以确定痴呆症的诊断。 将使用形态测量和免疫细胞化学技术来确定 SCN的神经胶质/神经元比值和加压素细胞数。 SCN退变的这些指标之间的统计相关性 经病理证实的阿尔茨海默病患者及其波幅和相位 将对内源性昼夜节律起搏器进行测试。

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.