Role of Brain in Bladder Control and Continence in Elderly Women

描述（由申请人提供）：急迫性尿失禁（Urge urinary incontinence, Ul）是最常见的老年尿失禁，对患者的生活和整个社会都有重大影响。表现为急尿和尿漏，伴有膀胱不自主收缩（逼尿肌过度活动），暗示大脑未能履行其控制膀胱的作用。快速出现的神经成像数据支持这一作用，至少在健康的年轻志愿者中是这样。该候选人一直在与一个率先研究大脑控制膀胱（同时尿动力学的功能性脑成像）的团队合作。他们共同表明，在老年女性急迫性尿失禁中，涉及绘制和监测膀胱传入信号的两个关键大脑区域对膀胱充血的反应不同，并伴有额叶皮质（负责排尿的执行控制）的反应受损，以及抑制急迫性和防止尿漏的代偿通路的招募。本提案旨在为候选人提供所需的额外技能，使其成为一名独立研究者，能够以创新的跨学科方式继续解决老年Ul的复杂综合征。活动由两个主要部分组成：1)学术，通过在指定导师的直接监督下进行相关程序和临床咨询，并辅以神经科学，统计学和成像技术课程，进一步发展神经影像学，尿动力学和尿失禁的理论和实践专业知识；2)科学，通过执行基于先前观察得出的假设的研究计划。拟议的研究计划强烈倾向于衰老，因为它的目的是：1)在更大的老年急迫性失禁受试者样本中测试现有的初步观察结果；2)研究年龄相关白质高强度（WMHI）在急迫性尿失禁和逼尿肌过度活动以及对额叶皮质（执行）功能的负面影响中的作用。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Ul的潜在原因和制定新的治疗策略。

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.