Behavioral therapy to treat urinary symptoms in Parkinson's disease

描述(由申请人提供) 据估计，40%的帕金森病(PD)患者患有下尿路症状(LUTS)，其中超过25%的患者有尿失禁(UI)。目前的治疗指南建议使用抗胆碱能药物治疗，这是基于专家的意见，因为到目前为止，还没有对成人PD患者进行任何治疗LUTS(包括UI)的随机对照试验。通常用于治疗泌尿症状的抗胆碱能药物会增加抗帕金森症治疗的抗胆碱能负担，从而增加疾病的认知和自主神经负担。与此同时，对尿失禁的行为干预--包括盆底肌肉锻炼(PFME)疗法--在随机对照试验中已被证明有效，且没有副作用。基于运动的UI行为干预要求个体学习运动技能(PFME)并实施适应性策略。作为改进循证治疗指南的第一步，候选人发表了一份唯一已知研究的摘要，该研究证明了使用基于运动的行为疗法治疗成人帕金森病患者尿失禁的可行性和潜在的治疗益处。行为疗法的随机对照试验将为优化患有PD和LUTS的退伍军人的护理提供一个合乎逻辑的下一步。该提案的项目目标包括：1.采用随机对照试验设计，评价基于运动的行为疗法治疗退伍军人帕金森病患者下尿路综合征的疗效。2.探讨帕金森病被试利用内隐记忆进行程序性学习的运动任务--运动型行为策略的学习和实施机制。3.在影响学习和记忆事实知识和程序技能的老化过程中获得知识和专业知识。4.了解自主神经功能障碍，掌握评估自主神经功能的技能。5.在纵向数据分析方面获得高级生物统计学培训。指导：指导团队将教师与研究方法、PD患者的护理和排尿功能障碍的管理方面的专业知识结合起来。导师包括：Theodore M.Johnson，II，医学博士，公共卫生硕士(初级，老年病学)，Kathryn L.Burgio，博士(行为心理学)，和Jorge L.Juncos，医学博士(运动障碍)。顾问：Gerald McGwin博士(生物统计学)和Felicia Goldstein博士(神经心理学)。职业生涯和研究计划：建议进行一项随机对照试验，以评估以盆底肌肉锻炼为基础的行为疗法治疗成人帕金森病患者下尿路综合征的疗效。根据尿失禁严重程度、帕金森病严重程度和性别进行分层后，60名受试者(每组30名)将被随机分成接受行为治疗或接受行为控制的8周。在完成行为治疗干预的参与者中计划进行为期6个月的随访。主要结果(尿失禁的频率)将使用七天的膀胱日记进行测量。程序学习的运动任务(连续反应时任务(SRTT))将在基线上给予所有参与者。探索性分析将评估SRTT的表现，将其作为成功实施基于运动的行为疗法以减少每周UI频率的预测因素。职业发展活动包括流行病学建模和纵向分析方面的生物统计学高级课程。高级课程作业和认知老化的定向阅读被提出。候选人将通过定向阅读、课程作业和实践培训来增加她对自主神经功能障碍的知识。候选人希望拟议的职业和研究计划将为她申请功绩审查资金做好准备，以建立作为调查人员的独立性，并提供必要的证据来支持患有PD的退伍军人LUT的治疗指南。

DESCRIPTION (provided by applicant) An estimated 40% of Parkinson's disease (PD) patients suffer from lower urinary tract symptoms (LUTS) including more than 25% who have urinary incontinence (UI). Current treatment guidelines, that recommend treatment with anticholinergic drugs, are based on expert opinion, because no randomized controlled trials of any therapy for LUTS (including UI) have been completed to date in adults with PD. Anticholinergic medications typically used to treat urinary symptoms can add to the anticholinergic burden of antiparkinsonian therapy, and thus to the cognitive and autonomic burdens of the illness. Meanwhile, behavioral interventions for UI - including pelvic floor muscle exercise (PFME) therapy - have proven efficacy in randomized controlled trials and are free of side effects. Exercise-based behavioral interventions for UI require individuals to learn motor skills (PFME) and implement an adaptive strategy. As a first step in improving evidence-based treatment guidelines, the candidate published an abstract of the only known study demonstrating the feasibility and potential therapeutic benefit of using exercise-based behavioral therapy to treat UI in adults with PD. Randomized controlled trials of behavioral therapy would provide a logical next step to optimize the care of veterans with PD and LUTS. The project goals for this proposal include: 1. Evaluate the efficacy of exercise-based behavioral therapy to treat LUTS among veterans with PD using a randomized controlled trial design. 2. Explore the mechanism utilized by PD participants to learn and implement the exercise-based behavioral strategy as a motor task of procedural learning using implicit memory. 3. Gain knowledge and expertise in aging processes that affect the ability to learn and remember both factual knowledge and procedural skills. 4. Gain understanding of autonomic dysfunction and technical skill in evaluating autonomic function. 5. Gain advanced biostatistical training in the analysis of longitudinal data. Mentoring: The mentoring team combines faculty with expertise in research methodology, the care of persons with PD, and management of voiding dysfunction. Mentors include: Theodore M. Johnson, II, MD, MPH (Primary, geriatrics), Kathryn L. Burgio, PhD (behavioral psychology), and Jorge L. Juncos, MD (movement disorders). Advisors: Gerald McGwin, PhD (biostatistics) and Felicia Goldstein, PhD (neuropsychology). Career and Research Plan: A randomized controlled trial is proposed to assess the efficacy of pelvic floor muscle exercise-based behavioral therapy to treat LUTS in adults with PD. After stratification by UI severity, PD severity, and gender, a group of 60 subjects (30 in each group) will be randomized to receive behavioral therapy or a behavioral control over 8 weeks. A 6-month follow-up is planned among participants who complete the behavioral therapy intervention. The primary outcome (frequency of UI) will be measured using a seven-day bladder diary. A motor task of procedural learning (Serial Reaction Time Task (SRTT)) will be administered at baseline to all participants. Exploratory analyses will assess performance on the SRTT as a predictor of success in implementing exercise-based behavioral therapy to reduce weekly UI frequency. Career development activities include advanced biostatistical coursework in epidemiologic modeling and longitudinal analyses. Advanced coursework and directed readings in cognitive aging are proposed. The candidate will increase her knowledge of autonomic dysfunction through directed readings, coursework, and practical training. The candidate expects the proposed career and research plan will prepare her to apply for Merit Review funding to establish independence as an investigator and provide needed evidence to support guidelines for the treatment of LUTS in veterans with PD.