Sleep and Bladder Study

项目总结 普遍、病态和昂贵(≥每年830亿美元)，紧迫性尿失禁(UUI)是一个主要问题， 尤其是对年长的女性。由于病因通常归因于膀胱痉挛，可用的治疗方法有 以膀胱为靶标，仅提供适度的好处。尽管反应不充分，遵守情况也很差，但 几十年来，UUI的治疗方法几乎没有变化，而一种新的整体方法来补充 或加强目前的治疗将对那些有衰弱症状的人的护理产生重大影响。 UUI与睡眠不佳有很强的双向关系，这是老年人普遍抱怨的问题。高达50%的 老年人报告睡眠不佳，这会使UUI的风险在5年内增加55%。大脑扮演着一个 睡眠在可控机制中起着至关重要的作用，已知睡眠会影响参与执行的通路 可控性控制。具体地说，睡眠不足与内侧前额叶皮质活动不足有关。 (MPFC)-我们已经确定的参与排尿执行控制的区域，以及潜在的治疗 对生物反馈辅助盆底肌肉治疗的反应。因此，我们假设睡眠不佳会抑制 控制膀胱，就像控制认知任务一样；解决睡眠问题将改善对 膀胱靶向UUI治疗同时进行的膀胱补充治疗。 我们的总体目标是：(A)评估行为睡眠干预对UUI的额外好处 护理标准(β3-肾上腺素能受体激动剂米拉贝格隆)为评估和解决提供证据 睡眠治疗UUI，以及(B)更好地了解大脑在睡眠对UU提供的影响中所起的作用 研究针对已识别的大脑通路的其他基于大脑的改良疗法的理论基础。 具体目的是检查辅助短暂行为治疗失眠(BBTI)的效果。 一线药物治疗：米雷贝格隆(1)尿失禁；(2)夜尿；(3)mPFC活性以确定疗效 通过评估睡眠对目前已知的介质的影响而产生的机制；以及(4)睡眠的持久性 治疗反应。 我们将随机选择100名年龄在≥60岁的女性，让她们接受8周的单独服用米拉贝格隆或服用 Mirabegron+BBTI，评估治疗前和治疗前的膀胱症状、睡眠以及脑功能和结构变化 干预后。我们还将探讨干预后6个月治疗反应的持久性。 这项研究将提供有史以来第一个关于综合多组分脑膀胱疗法的数据 以大小便失禁为靶点的已知大脑机制涉及到大小便失禁控制。它将评估临床 这种新配对的反应和持久性，并提供了对涉及的潜在途径的理解 在它的治疗机制上。

PROJECT SUMMARY Prevalent, morbid, and costly (≥$83 billion/year), urgency urinary incontinence (UUI) is a major problem, especially for older women. With etiology usually ascribed to bladder spasms, the available therapies are bladder-targeted and provide only a modest benefit. Despite inadequate response and poor adherence, there has been little change in therapeutic approach to UUI in decades, and a novel holistic approach to complement or enhance current treatment will have a significant impact on care of those with the debilitating symptoms. UUI has strong bidirectional relationship with poor sleep, a prevalent complaint in older adults. Up to 50% of older adults report poor sleep, which increases the risk of UUI by up to 55% over 5 years. The brain plays a vital role in the continence mechanism and sleep is known to affect the pathways involved in executive continence control. Specifically, sleep loss is associated with hypoactivity in the medial prefrontal cortex (mPFC) – a region we have identified to be involved in executive control of voiding, and potential therapeutic response to biofeedback-assisted pelvic floor muscle therapy. Hence, we hypothesize that poor sleep inhibits bladder control as it does with cognitive tasks; and addressing sleep will improve executive control of the bladder complementing concurrent bladder-targeted UUI therapy. Our overall goals are to: (a) assess the additional benefit of behavioral sleep intervention on UUI to the standard of care (β3- adrenoceptor agonist mirabegron) providing evidence for assessing and addressing sleep for treatment of UUI, and (b) better understand the brain’s role in the effect of sleep on UU providing rationale to investigate other ameliorative brain-based therapies targeting the identified brain pathways. Specific aims are to examine the effect of adjunctive Brief Behavioral Treatment of Insomnia (BBTI) with the first-line pharmacotherapy: mirabegron on (1) UUI; (2) nocturia; (3) mPFC activity to confirm therapeutic mechanisms by assessing the effect of sleep on currently understood mediators; and (4) durability of therapeutic response. We will randomize 100 women aged ≥ 60 years to receive 8 weeks of either mirabegron alone or mirabegron+BBTI, assessing bladder symptoms, sleep, and functional and structural brain changes pre- and post-intervention. We will also explore the durability of therapeutic response at 6-months post-intervention. The study will provide the first-ever data on a comprehensive multicomponent brain-bladder therapy for incontinence targeting the known brain mechanisms involve in continence control. It will evaluate clinical response and durability of this novel pairing and provide an understanding of the underlying pathways involved in its therapeutic mechanism.