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.

睡眠障碍是一种进行性痴呆疾病谱共有的破坏性症状， 它的存在常常促使家庭决定为患者寻求机构护理。正常睡眠-觉醒 调节的特征是振荡的、昼夜节律的、警觉的过程和线性的、睡眠诱导的过程 建筑物需要睡眠作为一个功能的持续时间之前清醒。在我们以前的研究中， 人群中，我们发现诊断特异性昼夜节律异常的男性，其中涉及中央， 额颞叶阿尔茨海默病患者睡眠-觉醒障碍病因学中的昼夜节律紊乱 变性和路易体病此外，我们还发现SCN细胞群的异常， 与阿尔茨海默病的特定昼夜节律和行为变化有关。我们现在希望建立 基于这些初步的发现，并将我们的研究扩展到SCN外的昼夜节律系统以及SCN 本身我们建议在这段供资期间测试四个假设。1)AD患者的多导睡眠图将 在核心体温昼夜节律有较大相位延迟的患者中， 其特征在于降低的睡眠效率增加了更长的睡眠等待时间。睡眠将更加分散， 与AD患者相比，FTD患者的觉醒次数增加。2)女性患者 可能AD患者的体温和活动时相与男性患者和正常人相似 对照组; 3）AD患者的夜间躁动和不安是由于AD患者的肾上腺素能神经支配丧失所致。 视交叉上核，并将在SCN中作为较低RIA血清素转运蛋白（5-HTT）检测到 与FTD患者和对照组相比。此外，AD患者的夜间躁动测量值更高 5-HTT较低的患者;和4）FTD患者的目标食欲素/下丘脑泌素水平降低 下丘脑、蓝斑、中线丘脑和/或中缝背核的周围区组织 与AD和对照组相比。活性和温度的解离程度将与 10 ss的食欲素/下丘脑泌素在具有相同痴呆诊断的患者中。为实现这些目标 我们将研究患有进行性痴呆疾病的患者，收集核心体温， 每6个月采集一次多导睡眠图和运动活动数据，随后进行尸检 除了基于诊断的神经病理学研究之外，还进行神经病理学研究。