rTMS as a Cognitive Rehabilitation Approach in Veterans with Parkinson's Disease

rTMS 作为帕金森病退伍军人的认知康复方法

• 批准号: 10454831
• 负责人: Sandra Lynn Kletzel
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454831
• 关键词: Activities of Daily Living; Address; Adverse event; Affect; Area; Automobile Driving; Behavioral; Brain; Cholinesterase Inhibitors; Chronic Disease; Clinical; Clinical Research; Cognition; Cognitive; Cognitive Therapy; Cognitive deficits; Coupled; Data; Dementia; Devices; Diffusion Magnetic Resonance Imaging; Double-Blind Method; FDA approved; Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Health; Healthcare; High Prevalence; Impaired cognition; Intervention; Knowledge; Learning; Left; Life; Literature; Measurement; Measures; Mental Depression; Mental disorders; Mentors; Motor; Neurocognitive; Neurodegenerative Disorders; Neurologic; Neurologic Dysfunctions; Neuronal Plasticity; Neuropsychological Tests; Neurosciences; Outcome; Outcome Measure; Parkinson Disease; Participant; Patients; Performance; Pharmacologic Substance; Pilot Projects; Population; Postdoctoral Fellow; Prefrontal Cortex; Protocols documentation; Quality of life; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recovery of Function; Rehabilitation Outcome; Rehabilitation therapy; Research; Research Personnel; Research Project Grants; Research Support; Research Training; Rest; Risk Factors; Safety; Secure; Standardization; Techniques; Testing; Therapeutic Effect; Training; Translating; United States National Institutes of Health; Veterans; base; care systems; career; cognitive enhancement; cognitive function; cognitive impairment in Parkinson' s; cognitive performance; cognitive rehabilitation; executive function; experience; follow-up; functional disability; functional outcomes; gray matter; improved; individualized medicine; interest; memory process; mild cognitive impairment; morphometry; motor impairment; multimodal neuroimaging; multimodality; neural network; neuroimaging; neurological rehabilitation; neuromechanism; neurophysiology; neuropsychiatric disorder; neuroregulation; performance tests; pre-clinical; primary outcome; processing speed; programs; relating to nervous system; repetitive transcranial magnetic stimulation; safety and feasibility; secondary outcome; skills; support network; trial design; white matter

More than 100,000 US Veterans living with Parkinson's disease (PD) currently receive PD-related care and services from the VA. In addition to motor complications, PD is characterized by progressive cognitive decline leading to long-term functional impairment and diminished quality of life. Approximately 20-55% of PD patients will develop mild cognitive impairment (PD-MCI) while up to 80% will develop dementia (PD-D). Since PD-MCI is a risk factor for developing PD-D, there is a critical need to develop treatments to improve cognition and slow or stop progression to PD-D. Limited treatment options for PD-MCI and PD-D and the possible need to tailor treatments to Veterans makes this an important research topic. Repetitive transcranial magnetic stimulation (rTMS) shows promise as an effective cognitive neurorehabilitation treatment. To date, no rTMS studies have assessed the effect of rTMS on cognitive function in PD-MCI. Nor has there been PD neurophysiological studies using rTMS to examine neural plasticity in cognitive neural networks. This CDA2 seeks to fill this gap by conducting a small scaled pilot randomized controlled trial (RCT) designed to assess the safety and therapeutic effects of rTMS on cognitive outcomes as well as on brain connectivity in Veterans with PD-MCI. PD-MCI participants will be randomized to either active rTMS or sham rTMS. Participants will complete a standardized neurocognitive battery assessment at baseline, endpoint (immediately after the 24 day intervention) and at a one month follow-up. The primary outcome is change in executive function. Secondary outcomes include performance on other cognitive domain tasks and a proximal measure of real-life function that captures relevant functional changes related to cognitive impairment in PD. Multi-modal neuroimaging, in a subsample of participants, will be used to study neural connectivity changes induced by rTMS. Changes in resting state functional connectivity, grey matter volume via voxel-based morphometry and white matter integrity via diffusion tensor imaging will be assessed at baseline and endpoint. To inform how to optimize rTMS treatment in PD-MCI, these changes will be correlated with changes in cognitive performance. Dr. Kletzel is an excellent candidate for a CDA2. She has been building a strong foundation for establishing a career as a VA clinical neuroscientist in the field of neurorehabilitation. Her preclinical neuroscience background combined with her post-doctoral and CDA1 clinical research training makes her uniquely suited to successfully address the research objectives. Dr. Kletzel's long-term career goal is to develop and optimize cognitive rehabilitation treatments for Veterans with PD so as to improve their function and quality of life. Her immediate career goals are to conduct her first small clinical RCT and use these data both to contribute to the field of neurocognitive rehabilitation as well as to secure a VA Merit grant as an independent investigator. To achieve these career goals, Dr. Kletzel has developed critical learning objectives set forth in her career plan. These include building upon and enhancing her clinical knowledge of PD and cognitive rehabilitation, expanding her skills of acquiring and analyzing multi-modal advanced neuroimaging data and developing her skills to conduct measurement research. Dr. Kletzel has assembled an impressive mentoring team to support her research and career plans. The team includes experts in the areas of PD and cognition, neuromodulation, neuroimaging and outcome measures. Completion of this CDA2 is expected to advance rehabilitative health care of Veterans who are affected by cognitive decline by providing necessary first steps towards developing a neuromodulatory cognitive intervention that has great potential to translate into clinical cognitive rehabilitation programs for Veterans with the goal of maximizing functional outcomes and improving quality of life.

目前有超过10万名患有帕金森氏病(PD)的美国退伍军人接受PD相关护理和 退伍军人事务部提供的服务。除运动并发症外，帕金森病的特点是进行性认知能力下降。 导致长期的功能损害和生活质量下降。大约20%-55%的PD 患者将发展为轻度认知障碍(PD-MCI)，而高达80%的患者将发展为痴呆症(PD-D)。 由于PD-MCI是发展PD-D的危险因素，因此迫切需要开发治疗方法以改善 认知和延缓或停止进展为PD-D。PD-MCI和PD-D的治疗选择有限 可能需要为退伍军人量身定做治疗方案，这使得这成为一个重要的研究课题。重复经颅 磁刺激(RTMS)是一种有效的认知神经康复治疗方法。到目前为止， 目前尚无rTMS研究评估rTMS对PD-MCI患者认知功能的影响。也没有警局 使用rTMS检查认知神经网络中神经可塑性的神经生理学研究。此CDA2 寻求通过进行小规模试点随机对照试验(RCT)来填补这一空白，该试验旨在评估 RTMS对退伍军人认知功能和脑连通性的安全性和疗效 PD-MCI。PD-MCI参与者将被随机分为活动rTMS组和假rTMS组。参与者将 在基线、终点(24天后立即)完成标准化的神经认知成套评估 干预)和一个月的随访期。主要结果是执行功能的改变。次要的 结果包括在其他认知领域任务上的表现和对现实生活功能的近距离测量 这捕捉到了与帕金森病认知障碍相关的功能变化。多模式神经成像，在 参与者的一个子样本将被用来研究rTMS诱导的神经连接变化。中的更改 静息状态功能连接、基于体素的形态测量的灰质体积和白质 通过扩散张量成像的完整性将在基线和终点进行评估。告知如何优化 RTMS治疗PD-MCI时，这些改变将与认知表现的改变相关。Dr。 Kletzel是CDA2的绝佳候选者。她一直在为建立自己的事业奠定坚实的基础 作为退伍军人事务部神经康复领域的临床神经学家。她的临床前神经科学背景 结合她的博士后和CDA1临床研究培训，使她独特地适合成功 阐述研究目标。Kletzel博士的长期职业目标是开发和优化认知 对退伍军人帕金森病患者进行康复治疗，以改善其功能和生活质量。她 目前的职业目标是进行她的第一个小型临床随机对照试验，并使用这些数据来为 在神经认知康复领域，以及作为一名独立研究人员获得退伍军人管理局奖励金。至 为了实现这些职业目标，Kletzel博士在她的职业规划中制定了关键的学习目标。 这些包括建立和加强她对帕金森病和认知康复的临床知识， 扩展她获取和分析多模式高级神经影像数据的技能，并发展她 具备进行测量研究的技能。Kletzel博士组建了一个令人印象深刻的指导团队来支持 她的研究和职业规划。该团队包括帕金森病和认知、神经调节、 神经成像和结果测量。这一CDA2的完成有望促进康复健康 护理受认知衰退影响的退伍军人，提供必要的第一步 神经调节性认知干预，具有转化为临床认知的巨大潜力 退伍军人康复计划，目标是最大限度地提高功能结果和改善质量 生活。