Role of Brain in Bladder Control and Continence in Elderly Women

描述(申请人提供)：急迫性尿失禁(Ul)是老年性Ul最常见的形式，对患者的生活和整个社会都有重大影响。它表现为排尿急迫和尿漏，伴随着不自主的膀胱收缩(逼尿肌过度活动)，意味着大脑未能发挥其控制膀胱的作用。迅速涌现的神经成像数据支持这种作用，至少在健康的年轻志愿者中是这样。这位候选人一直在与一个率先研究大脑对膀胱的控制(同时进行尿动力学功能脑成像)的团队合作。他们共同表明，在患有Ul的老年女性中，参与映射和监测膀胱传入信号的两个关键脑区对膀胱充盈的反应不同，同时额叶皮质(负责执行排尿控制)的反应受损，并招募代偿路径以抑制紧迫感和防止尿漏。本提案旨在为候选人提供成为一名独立调查员所需的额外技能，能够继续以创新的、跨学科的方式处理老年性UL的复杂综合征。活动分为两个主要部分：1)学术，进一步发展神经成像、尿动力学和尿失禁方面的理论和实践专门知识，通过在指定导师的直接监督下进行相关程序和临床咨询获得，并得到神经科学、统计学和成像技术课程的支持；2)科学，根据先前观察得出的假设，执行研究计划。拟议的研究计划强烈针对老龄化，因为它的目标是：1)在更大的老年冲动失禁受试者中测试现有的初步观察结果；以及2)调查与年龄相关的白质高强度(WMHI)在冲动Ul中的作用，因为已知它们与冲动失禁和逼尿肌过度活动有关，以及它们对额叶皮质(执行)功能的负面影响。相关性：老年性尿失禁影响了15%的美国老年人，因此是一个重要的公共卫生问题，在过去的半个世纪里，治疗效果几乎没有进步。拟议的培训将为候选人提供学术发展和一套新的技能，用于调查老年性UL的潜在原因和开发新的治疗策略。

DESCRIPTION (provided by applicant): Urge urinary incontinence (Ul) is the most common form of geriatric Ul, with significant impact on patients' lives and on society as a whole. It is manifested by urgency to void and urine leakage, associated with involuntary bladder contraction (detrusor overactivity), implying failure of the brain to fulfill its role in controlling the bladder. Rapidly emerging neuroimaging data support this role, at least in healthy young volunteers. The candidate has been working with a team that has pioneered the study of brain control of bladder (functional brain imaging with simultaneous urodynamics). Together they have shown, in older women with urge Ul, a different response to bladder filling in 2 key brain regions involved in mapping and monitoring bladder afferent signals, combined with impaired response in frontal cortex (responsible for executive control of voiding) and recruitment of compensatory pathways to suppress urgency and prevent urine leakage. The present proposal is designed to provide the candidate with the additional skills needed to become an independent investigator capable of continuing to address the complex syndrome of geriatric Ul in an innovative, cross-disciplinary manner. Activities are structured in two major components: 1) academic, with further development of theoretical and practical expertise in neuroimaging, urodynamics and urinary incontinence, obtained by performing the relevant procedures and clinical consults under the direct supervision of designated mentors, and supported by coursework in neuroscience, statistics and imaging techniques; and 2) scientific, by carrying out a research plan based on hypotheses derived from previous observations. The proposed Research Plan is strongly oriented toward aging, as it aims: 1) to test existing preliminary observations in a larger sample of older urge incontinent subjects; and 2) to investigate the role of age-associated white matter hyperintensities (WMHI) in urge Ul, because of their known association with urge incontinence and detrusor overactivity and their negative effect on frontal cortex (executive) function. Relevance: geriatric urinary incontinence affects 15% of US elderly and thus represents an important public health issue for which therapeutic efficacy has advanced little in the past half century. The proposed training ill provide the candidate with academic development and a novel set of skills to use in investigating the potential causes of geriatric Ul and in developing new treatment strategies.