Cognitive, urinary, and functional trajectories of older women using pharmacologic treatment strategies for urgency incontinence

项目摘要 60岁以上的女性中有五分之一患有急迫性尿失禁，这种情况与以下疾病有关： 抑郁、社交孤立、身体机能下降和丧失独立生活能力。目前 最常用的急迫性尿失禁的治疗是抗胆碱能药物， 抑制膀胱的不自主收缩。不幸的是，多项观察性研究表明， 抗胆碱能膀胱治疗可能对认知有不良影响，这是基于 老年痴呆症患者开这些药。因此，人们普遍担心， 老年失禁患者服用抗胆碱能药物希望改善膀胱状况 控制可能会使自己面临更大的风险，由于认知障碍的功能妥协。 然而，迄今为止，将抗胆碱能膀胱药物与痴呆症联系起来的数据来自于 回顾性观察分析而不是前瞻性试验。少数（主要是行业赞助） 使用抗胆碱能膀胱治疗直接评估老年人认知功能的研究， 小而矮，使用相对不敏感的认知筛查措施，限制了他们的能力， 发现认知上有意义的变化。而另一种治疗尿失禁的非抗胆碱能药物 (theβ-3-激动剂药物米拉贝隆）现已上市，很少有研究比较这种药物的作用。 药物治疗的抗胆碱能膀胱治疗，并没有涉及比较前瞻性 评估老年人的认知能力。在缺乏不利认知影响的严格证据的情况下， 抗胆碱能膀胱药物继续被广泛地开给社区中的老年患者， 包括那些已知有认知障碍、阿尔茨海默病和相关痴呆症的人。 为了解决这个问题，我们将进行一项严格的、前瞻性的随机研究， 认知，泌尿和功能轨迹在约270老年失禁妇女没有预先存在的痴呆症。 基线时频繁尿急性尿失禁且认知功能正常或轻度受损的女性将被纳入研究。 分配接受标准抗胆碱能药物、β-3激动剂或无药物治疗（安慰剂）， 此外，患者为导向，循证信息的行为管理尿失禁。超过 1个月、6个月和9个月时，我们将比较两组患者的认知、泌尿和其他功能和生活质量结果。 抗胆碱能治疗与β-3-激动剂治疗和安慰剂相比。这项研究解决了紧迫的 需要严格的证据来确定药物性尿失禁治疗策略对两者的影响， 认知障碍和尿失禁，作为两种最常见的（和经常共病）的条件， 促使老年妇女从独立生活过渡到进入长期护理设施。

PROJECT SUMMARY One in five women over the age of 60 suffers from urgency incontinence, a condition associated with depression, social isolation, physical function decline, and loss of ability to live independently. Currently, the most commonly used treatments for urgency incontinence are anticholinergic medications designed to suppress involuntary contractions of the bladder. Unfortunately, multiple observational studies have suggested that anticholinergic bladder therapy may have adverse effects on cognition, based on higher rates of diagnosed dementia in older patients prescribed these medications. As a result, there is widespread concern that older incontinent patients who take anticholinergic medications in the hopes of improving their bladder control may be exposing themselves to greater risk of functional compromise due to cognitive impairment. To date, however, the data linking anticholinergic bladder medications with dementia are derived from retrospective observational analyses rather than prospective trials. The few (and primarily industry-sponsored) studies directly assessing cognitive function in older adults using anticholinergic bladder therapy have been small and short and have used relatively insensitive cognitive screening measures, limiting their ability to detect meaningful changes in cognition. While an alternate, non-anticholinergic medication for incontinence (the beta-3-agonist drug mirabegron) is now available, very little research has compared the effects of this medication to that of anticholinergic bladder therapy, and none has involved comparative prospective assessments of cognition in older adults. In the absence of rigorous evidence of adverse cognitive effects, anticholinergic bladder medications continue to be widely prescribed to older patients in the community, including those with known cognitive impairment, Alzheimer’s disease, and related dementias. To address this issue, we will conduct a rigorous, prospective, randomized study to evaluate extended cognitive, urinary, and functional trajectories in ~270 older incontinent women without pre-existing dementia. Women with frequent urgency incontinence and normal or mildly impaired cognitive function at baseline will be assigned to receive standard anticholinergic, beta-3 agonist, or no pharmacologic treatment (placebo) in addition to patient-directed, evidence-based information about behavioral management of incontinence. Over 1, 6, and 9 months, we will compare cognitive, urinary, and other functional and quality-of-life outcomes of anticholinergic therapy in comparison to beta-3-agonist therapy and placebo. This research address the urgent need for rigorous evidence to determine the effects of pharmacologic incontinence treatment strategies on both cognitive impairment and incontinence, as two of the most common (and frequently comorbid) conditions that cause older women to transition from living independently to entering long-term care facilities.