REHABILITATION OF CIRCADIAN BLINDNESS IN OLDER PEOPLE

老年人昼夜节律失明的康复

• 批准号: 2855798
• 负责人: Elizabeth B. Klerman
• 金额: $ 10.85万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-01-20 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2855798
• 关键词: auditory stimulus; blindness; body temperature; chronotherapy; circadian rhythms; cognition; cortisol; electroencephalography; electromyography; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; melatonin; performance; psychomotor function; psychophysiology; saliva; sleep; sleep disorders; stimulus /response; urinalysis; wakefulness

Both blindness and aging are frequently associated with sleep disturbances for which medicines with undesired and potentially dangerous side effects are often prescribed. In blind individuals, these sleep disturbances may be due to misalignment of the endogenous circadian pacemaker and its outputs with respect to the sleep-wake schedule, for they lack the periodic light input necessary for entrainment of the circadian clock to the 24 hour day. Without such light input, circadian rhythms of blind individuals may "free-run" at a period of the endogenous circadian pacemaker which is near-to but different from 24.00 hours. In these free- running blind people, there may be a chronic sleep and circadian rhythm disturbance whose severity varies with the relative relationship between the sleep/wake cycle and the internal clock. With aging, there is an increase in blindness and therefore the prevalence of this disability. In this research proposal, I plan to study blind older people to verify the presence of free-running circadian rhythms and then treat them with melatonin, an endogenous hormone, both to alleviate the chronic sleep problems that occur when they maintain a 24-hour schedule and to improve cognitive performance during the following waking hours. Specifically, I plan to test the hypotheses that (1) the majority of older blind patients without conscious light perception are unable to synchronize their circadian pacemakers to the 24-hour day; (2) light input to the hypothalamus and pineal is functionally absent in these blind people; (3) non-visual cognitive and psychometric performance decrements, as well as sleep, endocrine and metabolic abnormalities are found in these blind people; and (4) pre-sleep administration of physiological doses of melatonin will improve sleep, cognitive and psychomotor performance measures. Each older blind subject will be studied several times, first to establish the presence of free-running circadian rhythms and associated disorders, then during treatment with melatonin to verify improvement of sleep variables, such as sleep latency and sleep efficiency, and cognitive and performance measures. The results will be applicable to the blind community, to the older population with and without vision or light exposure problems, as well as to younger individuals on non-24 hour schedules, such as people on rotating shift work or night work schedules. Improving the sleep and performance measures of this large segment of the population using physiologic amounts of a natural hormone rather than pharmacological doses of medicines with potentially dangerous side effects has the potential to rehabilitate and improve the lives of the many individuals and their families.

失明和衰老经常与睡眠障碍有关 对于那些具有不良和潜在危险副作用的药物， 经常被规定。在盲人中，这些睡眠障碍可能 是由于内源性昼夜节律起搏器及其 关于睡眠-觉醒时间表的输出，因为它们缺乏 周期性的光输入对于生物钟的夹带是必要的， 一天24小时。如果没有这样的光输入， 个体可以在内源性昼夜节律的一段时间内“自由奔跑” 接近但不同于24小时的起搏器。在这些自由- 跑步盲人，可能有慢性睡眠和昼夜节律 其严重程度随以下因素之间的相对关系而变化的干扰 睡眠/唤醒周期和内部时钟。随着年龄的增长， 失明的增加，因此这种残疾的流行。 在这个研究建议中，我计划研究失明的老年人，以验证 自由运行的昼夜节律的存在，然后用 褪黑激素是一种内源性激素，既能缓解慢性睡眠， 当他们保持一个24小时的时间表时发生的问题， 在接下来的清醒时间内的认知表现。我特别 计划检验以下假设：（1）大多数老年盲人患者 没有有意识的光感知， 昼夜节律起搏器到24小时的一天;（2）光输入到 下丘脑和松果体在这些盲人中功能缺失;（3） 非视觉认知和心理测量性能下降，以及 在这些盲人中发现睡眠、内分泌和代谢异常 人;和（4）睡前给予生理剂量的 褪黑激素将改善睡眠、认知和精神运动表现 措施 每个年长的盲人受试者将被研究多次，首先要确定 自由运行的昼夜节律和相关疾病的存在， 然后在用褪黑激素治疗以验证睡眠改善的过程中 变量，如睡眠潜伏期和睡眠效率，以及认知和 业绩计量。 研究结果将适用于盲人群体， 有和没有视力或光照问题的人群，以及 对于非24小时计划的年轻人，例如 轮班工作或夜间工作时间表。改善睡眠， 这一大部分人口的业绩衡量标准， 生理量的天然激素，而不是药理剂量 具有潜在危险副作用的药物有可能 恢复和改善许多人的生活， 家庭

项目成果

Nonphotic entrainment of the human circadian pacemaker.

人类昼夜节律起搏器的非光夹带。

• DOI: 10.1152/ajpregu.1998.274.4.r991
• 发表时间: 1998
• 期刊: The American journal of physiology
• 作者: Klerman,EB;Rimmer,DW;Dijk,DJ;Kronauer,RE;Rizzo3rd,JF;Czeisler,CA
• 通讯作者: Czeisler,CA

Circadian and sleep-dependent regulation of hormone release in humans.

• 发表时间: 1999
• 期刊: Recent progress in hormone research
• 作者: C. Czeisler;E. Klerman

Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects.

在完全失明的人类受试者中，昼夜节律褪黑激素分泌事件的持续时间没有增加。

• DOI: 10.1210/jcem.86.7.7659
• 发表时间: 2001
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Klerman,EB;Zeitzer,JM;Duffy,JF;Khalsa,SB;Czeisler,CA
• 通讯作者: Czeisler,CA

Circadian rhythms of women with fibromyalgia.

患有纤维肌痛的女性的昼夜节律。

• DOI: 10.1210/jcem.86.3.7293
• 发表时间: 2001
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Klerman,EB;Goldenberg,DL;Brown,EN;Maliszewski,AM;Adler,GK
• 通讯作者: Adler,GK

Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients.

人类昼夜节律起搏器在整个主观一天中对光敏感，没有瞬变的证据。

• DOI: 10.1152/ajpregu.1997.273.5.r1800
• 发表时间: 1997
• 期刊: The American journal of physiology
• 作者: Jewett,ME;Rimmer,DW;Duffy,JF;Klerman,EB;Kronauer,RE;Czeisler,CA
• 通讯作者: Czeisler,CA