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

超过100，000名患有帕金森病（PD）的美国退伍军人目前接受PD相关护理， 从VA的服务。除了运动并发症，PD的特征是进行性认知功能下降 从而导致长期功能损伤和生活质量下降。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（PD-D）。 由于PD-MCI是发展PD-D的风险因素，因此迫切需要开发治疗方法以改善PD-D。 认知和减缓或停止进展为PD-D。PD-MCI和PD-D的治疗选择有限， 为退伍军人量身定制治疗的可能需要使这成为一个重要的研究课题。重复经颅 磁刺激（rTMS）显示出作为有效的认知神经康复治疗的前景。到目前为止， 尚无rTMS研究评估rTMS对PD-MCI患者认知功能的影响。也没有PD 神经生理学研究使用rTMS检查认知神经网络中的神经可塑性。这个cda 2 旨在通过进行一项小规模的随机对照试验（RCT）来填补这一空白， rTMS对认知结果以及退伍军人脑连接的安全性和治疗效果 PD-MCI PD-MCI受试者将被随机分配至活性rTMS或假rTMS组。参与者将 在基线、终点（24天后立即）完成标准化神经认知成套测验评估 干预）和一个月的随访。主要结果是执行功能的改变。二次 结果包括其他认知领域任务的表现和现实生活功能的近端测量 其捕获与PD中的认知损害相关的相关功能变化。多模态神经成像， 参与者的子样本，将用于研究rTMS引起的神经连接变化。变化 静息状态功能连接，通过基于体素的形态测量和白色物质的灰质体积 将在基线和终点通过弥散张量成像评估完整性。告知如何优化 在PD-MCI的rTMS治疗中，这些变化将与认知表现的变化相关。博士 Kletzel是CDA 2的优秀候选人。她一直在为建立事业打下坚实的基础 作为退伍军人管理局神经康复领域的临床神经科学家她的临床前神经科学背景 结合她的博士后和CDA 1临床研究培训，使她独特地适合成功地 解决研究目标。Kletzel博士的长期职业目标是发展和优化认知能力， 康复治疗的退伍军人与PD，以改善他们的功能和生活质量。她 近期的职业目标是进行她的第一个小型临床随机对照试验，并利用这些数据为 神经认知康复领域，以及作为一个独立的研究者获得VA优异奖。到 为了实现这些职业目标，Kletzel博士在她的职业计划中制定了重要的学习目标。 这些措施包括建立和提高她的PD和认知康复的临床知识， 扩大她的技能，获取和分析多模态先进的神经成像数据，并发展她的 进行测量研究的技能。Kletzel博士组建了一支令人印象深刻的指导团队， 她的研究和职业规划该团队包括PD和认知，神经调节， 神经影像学和结果测量。完成该CDA 2有望促进康复健康 护理受认知能力下降影响的退伍军人，为他们提供必要的第一步， 神经调节认知干预，具有很大的潜力，转化为临床认知 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

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.