Sleep, Circadian Rhythms and Dementing Illnesses

睡眠、昼夜节律和痴呆症

• 批准号: 7470299
• 负责人: DAVID G HARPER
• 金额: $ 35.64万
• 依托单位: BEDFORD VA RESEARCH CORPORATION, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7470299
• 关键词: Affect; Age; Agitation; Alzheimer' s Disease; Area; Behavioral; Body Temperature; Carrier Proteins; Cessation of life; Characteristics; Circadian Rhythms; Data; Dementia; Deterioration; Diagnosis; Disease; Disruption; Dissociation; Elderly; Etiology; Family; Female; Functional disorder; Funding; Hour; Human; Hypothalamic structure; Illness impact; Immunohistochemistry; Indium; Institutionalization; Laboratories; Lewy Body Disease; Link; Measurement; Measures; Motor Activity; Nature; Numbers; Patient Care; Patients; Pattern; Periodicity; Phase; Physiological; Pick Disease of the Brain; Play; Polysomnography; Population; Principal Investigator; Process; REM Sleep; Radioimmunoassay; Regulation; Reporting; Role; Sleep; Sleep disturbances; Symptoms; System; Temperature; Testing; Thalamic structure; Thinking; Time; Tissues; Wakefulness; Work; base; behavior measurement; cost; disorder control; dorsal raphe nucleus; hypocretin; improved; locus ceruleus structure; male; men; nerve supply; phase change; programs; serotonin transporter; suprachiasmatic nucleus

Sleep disturbance is a disruptive symptom shared by the spectrum of progressive dementing illnesses, and its presence often precipitates decisions by families to seek institutional care for patients. Normal sleep-wake regulation is characterized by an oscillatory, circadian, alerting process and a linear, sleep-inducing process building need to sleep as a function of the duration of prior wakefulness. In our previous studies in this population, we have found diagnosis-specific circadian abnormalities in men which implicate central, circadian dysfunction in the etiology of sleep-wake disturbance in Alzheimer's disease, frontotemporal degeneration, and Lewy body disease. In addition, we have found abnormalities in SCN cellular populations in men linked with specific circadian and behavioral changes in Alzheimer's disease. We now wish to build upon these initial findings and expand our studies to the extra-SCN circadian system as well as the SCN itself. We propose for this funding period to test four hypotheses. 1) Polysomnographic sleep in AD will be more disturbed in patients with large phase-delays of their circadian core-body temperature rhythm characterized by reduced sleep efficiency add longer sleep latency. Sleep will be more fragmented in patients with FTD compared to AD patients with an increased number of awakenings. 2) Female patients with probable AD will have similady delayed phase of temperature and activity as male patients and normal controls; 3) Noctumal agitation and restlessness, seen in AD, results from loss of serotonergic innervation of the suprachiasmatic nuclei and will be detectable as lower RIA serotonin transporter protein (5-HTT) in SCN compared to FTD patients and controls. In addition,_ measurements of nocturnal agitation will be higher in AD patients with lower 5-HTT; and 4) Patients with FTD wilt have lowered levels of orexin/hypocretin in target tissue of perifonical area of the hypothalamus, locus coeruleus, midline thalamus and/or dorsal raphe nuclei compared to AD and controls. The extent of dissociation of activity and temperature will be related to the 10ss of orexin/hypocretin in patients carrying the same dementia diagnoses. To accomplish these objectives we will study patients with progressive dementing illnesses collecting core-body temperature, polysomnographic and locomotor activity data every 6 months and followed by post-mortem neuropathological studies in addition to diagnosis-based neuropathological studies.

睡眠障碍是通过逐渐痴呆疾病和 它的存在通常会导致家庭决定为患者寻求机构护理。正常的睡眠醒 调节的特征是振荡，昼夜节律，警报过程和线性诱导睡眠过程 建筑物需要睡眠作为先前清醒的持续时间。在我们以前的研究中 人口，我们发现男性的诊断特异性异常，这意味着中心， 阿尔茨海默氏病睡眠觉醒障碍病因的昼夜节律功能障碍，额颞 变性和刘易身体疾病。此外，我们发现SCN细胞种群异常 在与特定昼夜节律和阿尔茨海默氏病的行为变化有关的男性中。我们现在想建造 根据这些初步发现，并将我们的研究扩展到超级SCN昼夜节律系统以及SCN 本身。我们建议在此资金期间检验四个假设。 1）广告中的多摄影学睡眠将是 对昼夜节律核心体温度节奏的大相期延期的患者更加干扰 以降低的睡眠效率为特征，增加了更长的睡眠潜伏期。睡眠会更分散 与AD患者相比，FTD患者的觉醒次数增加。 2）女性患者 有可能的AD将与男性患者和正常患者具有相似的温度和活性延迟阶段 控件； 3）在AD中看到的夜量的躁动和不安，是由于血清素能神经神经神经神经的丧失而导致的 可检测到SCN中的RIA 5-羟色胺转运蛋白（5-HTT），可检测到SCN的较低的核核。 与FTD患者和对照组相比。此外，_夜间搅动的测量值将在AD中更高 较低5-HTT的患者； 4）FTD WILT患者的靶标的Orexin/dybocretin降低 下丘脑，基因座，中线丘脑和/或背侧raphe核的牙线区域的组织 与AD和对照组相比。活性和温度解离的程度将与 携带相同痴呆诊断的患者中的10S OREXIN/低载素。实现这些目标 我们将研究患有逐渐痴呆疾病的患者，以收集核心体温， 每6个月一次多摄影和运动活动数据，然后进行验尸 除基于诊断的神经病理学研究外，神经病理学研究。