Impact of Behavioral Treatment of Insomnia on Nighttime Urine Production

项目总结 夜尿症普遍、病态和昂贵(2012年为610亿美元/年)，是一个主要问题，特别是对老年人来说。 它增加了跌倒、骨折、抑郁症、养老院安置和死亡的风险。然而，管理 夜尿症仍不充分。大多数夜尿症的行为和药物治疗都集中在与膀胱相关的 病因，最常见的原因是夜间多尿(NP)，或睡眠时尿量增加 在过去的50年里，人们对此仍然知之甚少，也没有得到充分的对待，几乎没有取得什么进展。颠覆 白天排泄模式，夜间尿量较高的情况在老年人中常见。在中国学习的同时 年轻人的研究表明，睡眠在调节老年人夜间尿液排泄方面起着关键作用。 睡眠不良在NP中的作用还没有得到充分的研究。 尿液的产生遵循一种昼夜节律模式，即从清醒到睡眠的转变之后是一个明显的 减少水、电解质和其他渗透活性物质的排泄。青年学生的研究 人们已经确定生理尿液的产生遵循昼夜节律，这种节律是有调节的 通过控制水分和盐分排泄的激素，如精氨酸加压素的日变化， 肾素-血管紧张素-醛固酮系统和心钠素。睡眠不足减缓夜间睡眠激增 这些激素会改变水和盐的排泄，从而增加夜间尿量 导致NP。 最近的证据表明，睡眠质量差，频繁的睡眠中断，特别是在睡眠的第一部分 夜间和第一次不间断睡眠时间较短与NP有关，但其病理生理学 没有完全理解。此外，在睡眠不佳的老年人中，我们已经证明了一种行为 仅针对睡眠的干预(BBTI-失眠的简要行为治疗和有效 失眠的多模式行为治疗)不仅能改善睡眠，还能改善夜尿症。因此，我们假设 睡眠第一阶段的睡眠中断会影响夜间尿液的激素调节 导致NP的生产。此外，我们假设，延长第一次不间断睡眠的干预措施 经期会减少NP，因此会出现夜尿症。 本提案的目的是：1)审查BBTI对第一个 夜尿症老年患者的不间断睡眠周期和NP；2)建立NP和首次睡眠持续时间 不间断睡眠是BBTI影响夜尿症的机制。我们的假设是BBTI改善了 夜尿症不仅通过改善睡眠(特别是第一个不间断睡眠阶段的持续时间)，而且还 通过减少NP。 为了实现我们的目标，我们将招募60名有夜尿症和NP的社区居住成年人(65岁)。沉睡 主观上使用失眠严重程度指数进行评估，客观上使用7天睡眠日记和手腕进行评估 活动记录仪。同时，我们将收集3天的膀胱日记数据，以记录它们的排尿模式和容量 在白天和晚上。参与者将被随机接受为期4周的行为睡眠干预BBTI 由训练有素的治疗师或信息控制干预。参与者将重复研究措施 干预后。 这项研究结果将对睡眠不佳的共同病理机制提供重要的见解， 夜尿症和夜间排尿。我们将利用这些发现来构建一个更大的R01，以便在 NP的老年生物机制，调节盐和水排泄的激素的昼夜节律，以及 睡眠治疗对这些节律的影响。

PROJECT SUMMARY Prevalent, morbid, and costly ($61 billion/year in 2012), nocturia is a major problem, especially for older adults. It increases the risk of falls, fractures, depression, nursing home placement, and death. Yet management of nocturia remains inadequate. Most behavior and pharmacotherapies for nocturia focus on bladder-related etiologies, and it’s most prevalent attribute nocturnal polyuria (NP), or increased urine production during sleep remains poorly understood and inadequately treated with little advancement over the last 50 years. Disruption of diurnal excretory pattern, with higher nighttime urine production is common in older adults. While studies in young adults show that sleep plays a critical role in regulating nighttime urine production, among older adults the role of poor sleep in NP is under-investigated. Urine production follows a circadian pattern in which transition from wake to sleep is followed by a pronounced decrease in excretion of water, electrolytes and other osmotically active substances. Studies in young population have established that physiological urine production follows a circadian rhythm, which is regulated by diurnal variation in secretion of hormones controlling water and salt excretion such as arginine vasopressin, renin-angiotensin-aldosterone system, and atrial natriuretic peptide. Sleep deprivation blunts nocturnal surge of these hormones and consequently alter water and salt excretion thereby increase nighttime urine volume leading to NP. Recent evidence suggests that poor sleep quality, frequent sleep interruptions especially in the first part of the night and shorter duration of first uninterrupted sleep period are associated with NP but its pathophysiology is not fully understood. Additionally, among older adults with poor sleep, we have shown that a behavioral intervention directed solely towards sleep (BBTI- brief behavioral treatment of insomnia an efficacious multimodal behavioral treatment for insomnia) not only improves sleep, but also nocturia. Hence, we postulate that sleep interruptions in the first part of the sleep impacts the hormonal regulation of nighttime urine production causing NP. In addition, we postulate that interventions to prolong the first uninterrupted sleep period will decrease NP and hence nocturia. The, aims of the present proposal are to: 1) examine the impact of BBTI on duration of the first of uninterrupted sleep period and NP in elderly with nocturia; and 2) establish NP and duration of first uninterrupted sleep as mechanisms by which BBTI impacts nocturia. Our hypothesis is that BBTI improves nocturia not only by improving sleep, (and specifically, duration of the first uninterrupted sleep period), but also by decreasing NP. To accomplish our goals we will recruit 60 community dwelling adults (aged >65) with nocturia and NP. Sleep will be assessed subjectively with the Insomnia Severity Index and objectively by 7-day sleep diary and wrist actigraph. Concurrently we will collect 3-day bladder diary data to document their voiding pattern and volume during day and night. Participants will be randomized to receive the 4-week behavioral sleep intervention BBTI by a trained therapist or an information control intervention. The participants will repeat the study measures post-intervention. The study results will provide important insights into shared pathological mechanisms underlying poor sleep, nocturia and nighttime urine production. We will use these findings to construct a larger R01 to explore in the elderly biological mechanisms of NP, circadian rhythms of hormones regulating salt and water excretion, and the impact of sleep treatment on these rhythms.