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（UI）是老年UI的最常见形式，对患者的生活和整个社会具有重大影响。它表现为排尿紧迫感和尿液渗漏，与不自主的膀胱收缩（逼尿肌过度活动）相关，这意味着大脑无法履行其控制膀胱的作用。快速出现的神经影像学数据支持这一作用，至少在健康的年轻志愿者中。该候选人一直与一个团队合作，该团队开创了膀胱的大脑控制研究（功能性脑成像与同步尿动力学）。他们一起显示，在患有急迫性尿失禁的老年女性中，在参与映射和监测膀胱传入信号的2个关键脑区域中对膀胱充盈的不同反应，与额叶皮层（负责排尿的执行控制）中的受损反应和抑制急迫性和防止尿渗漏的补偿途径的募集相结合。本提案旨在为候选人提供成为独立调查员所需的额外技能，能够以创新，跨学科的方式继续解决老年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，尿动力学和尿失禁的理论和实践专业知识，通过在指定导师的直接监督下执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）科学性，即根据以前的观察得出的假设执行研究计划。拟定的研究计划强烈倾向于老龄化，因为其目的是：1）在更大样本的老年急迫性尿失禁受试者中测试现有的初步观察结果; 2）研究年龄相关的白色高信号（WMHI）在急迫性尿失禁中的作用，因为已知它们与急迫性尿失禁和逼尿肌过度活动相关，并对额叶皮层（执行）功能产生负面影响。 相关性：老年尿失禁影响15%的美国老年人，因此代表了一个重要的公共健康问题，在过去的半个世纪中，其治疗效果几乎没有进展。所提出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.