Cognitive Biomarker Targets for Treatment in Veterans with Parkinson's Disease

治疗帕金森病退伍军人的认知生物标志物目标

• 批准号: 9067161
• 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: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067161
• 关键词: Address; Advisory Committees; Affect; Area; Attention; Behavior; Behavioral; Biological Markers; Biological Neural Networks; Brain; Brain region; Caregivers; Caring; Cholinesterases; Chronic Disease; Cognition; Cognitive; Cognitive deficits; Coupled; Craniocerebral Trauma; Data; Dementia; Development; Elements; FDA approved; Functional Magnetic Resonance Imaging; Goals; Health; Imaging Techniques; Impaired cognition; Intervention; Knowledge; Language; Life; Literature; Memory; Mental disorders; Mentors; Mood Disorders; Moods; Motor; Movement Disorders; Nature; Neurobiology; Neurodegenerative Disorders; Neurologic; Neurologic Dysfunctions; Neurological rehabilitation; Neuronal Plasticity; Neuropsychological Tests; Neurorehabilitation; Outcome; Parkinson Disease; Participant; Patients; Persons; Pharmacologic Substance; Phenotype; Population; Post-Traumatic Stress Disorders; Prevalence; Protocols documentation; Quality of life; Randomized; Randomized Controlled Trials; Recording of previous events; Recruitment Activity; Rehabilitation Outcome; Rehabilitation therapy; Research; Research Project Grants; Rest; Risk; Risk Factors; Safety; Scientific Advances and Accomplishments; Services; Severities; Short-Term Memory; Site; Staging; Techniques; Testing; Therapeutic; Training; Traumatic Brain Injury; Veterans; Visuospatial; Work; aging population; base; brain behavior; career; cognitive enhancement; cognitive function; cognitive rehabilitation; cognitive task; cohort; combat; daily functioning; executive function; improved; individualized medicine; innovation; insight; interest; knowledge base; mild cognitive impairment; motor disorder; motor symptom; neuropsychiatric disorder; neuropsychological; non-motor symptom; prevent; primary outcome; public health relevance; rehabilitation strategy; relating to nervous system; repetitive transcranial magnetic stimulation; secondary outcome; targeted biomarker; therapeutic target; tool

 DESCRIPTION: More than 100,000 Veterans living with Parkinson's disease (PD) currently receive PD-related care and services from the VA. Management of PD includes treatment of both motor and non-motor symptoms. Mild cognitive impairment (PD-MCI) is a common non-motor symptom in PD that negatively impacts functioning, is a main determinant of quality of life, and is a risk factorfor developing dementia. In the civilian population, over a quarter of PD patients have PD-MCI; estimates are unknown in Veterans. It is also unknown if combat- related risk factors impact the nature PD-MCI (i.e., severity or types of cognitive domains), thus studying PD- MCI in Veterans may be particularly important. Limited treatment options for PD-MCI in the civilian population and the possible need to tailor treatments to Veterans with PD-MCI makes this an important research topic. Understanding PD-MCI can offer insight into the brain mechanisms at the earliest stage of cognitive decline. For example, cognitive function is supported by brain regions that comprise neural networks. These networks are functionally connected even when a cognitive task is not being performed (i.e., when a person is at rest). Changes in the resting state functional connectivity (rsFC) of cognitive networks are associated with changes in cognitive function. Understanding unique differences in the rsFC of cognitive networks associated with PD-MCI will aid in elucidating the neurobiology of this condition. Such information can be used to develop early rehabilitation interventions, such as repetitive transcranial magnetic stimulation (rTMS), that focus on preventing or delaying the onset of PD-D. rTMS is a non-pharmacological and non- invasive stimulation technique that can induce neuronal plasticity in targeted brain regions and networks. rTMS shows promise as a tool for cognitive enhancement in people with neurological conditions. The objectives of the current CDA2 proposal are to enhance our understanding of the mild cognitive deficits that most frequently occur in Veterans with PD and to determine the altered rsFC of critical brain regions that support cognitive function. Information gained about these brain and behavior relationships will be used to guide the development of a protocol for a cognitive rehabilitation intervention using rTMS. To carry out these objectives, Veterans with PD will be recruited and cognitive behavior will be characterized using neuropsychological tests. The underlying neurobiology of the behavior will be characterized using advanced functional magnetic resonance imaging (fMRI) techniques and rsFC analysis. Multiple approaches for functional connectivity analyses will be undertaken. Specifically, disruptions in functional connectivity of regions within or between cognitive networks that are correlated with cognitive impairment will be determined. These brain and behavior characterizations will be evaluated collectively to develop an rTMS protocol such that a cortical stimulation site as well as stimulation parameters will be determined. A pilot randomized control trial to determine safety, feasibility and efficacy of rTMS to improve cognitive function will be conducted. Participants will be treated with either active or sham rTMS for 10 daily sessions over the course of two weeks. It is expected that this innovative project will contribute a missing, fundamental element to our base knowledge, without which mild cognitive impairment in Veterans with PD cannot be understood. The acquisition of such knowledge is critical for developing and optimizing cognitive rehabilitation treatments for Veterans with PD-MCI, with an ultimate goal of improving quality of life. Findings related to this CDA2 proposal will potentially inform neurorehabilitation of other conditions in which MCI and dementia occur.

 说明： 超过10万名患有帕金森氏病(PD)的退伍军人目前正在接受退伍军人管理局与PD相关的护理和服务。帕金森病的治疗包括运动性和非运动性症状的治疗。轻度认知障碍(PD-MCI)是帕金森病常见的非运动症状，对功能有负面影响，是生活质量的主要决定因素，也是发展为痴呆的危险因素。在平民人口中，超过四分之一的PD患者患有PD-MCI；退伍军人中的估计数尚不清楚。与战斗相关的危险因素是否影响PD-MCI的性质(即认知领域的严重程度或类型)也是未知的，因此研究退伍军人的PD-MCI可能特别重要。平民人口中帕金森病-MCI的治疗选择有限，以及可能需要为患有帕金森病-MCI的退伍军人量身定做治疗方案，这使这成为一个重要的研究课题。了解PD-MCI可以提供对认知衰退早期阶段的大脑机制的洞察。例如，认知功能由组成神经网络的大脑区域支持。这些网络在功能上是相连的，即使在认知任务没有执行的时候(即，当一个人休息的时候)。认知网络静息状态功能连接性(RsFC)的变化与认知功能的变化有关。了解与PD-MCI相关的认知网络rsFC的独特差异将有助于阐明这种疾病的神经生物学。这些信息可用于制定早期康复干预措施，如重复经颅磁刺激(RTMS)，重点是预防或推迟PD-D的发病。RTMS是一种非药物和非侵入性的刺激技术，可以在靶向的大脑区域和网络中诱导神经元的可塑性。RTMS显示出作为神经疾病患者认知增强工具的前景。目前CDA2提案的目标是加强我们对退伍军人帕金森病患者中最常见的轻度认知缺陷的了解，并确定支持认知功能的关键大脑区域的改变的rsFC。关于这些大脑和行为关系的信息将被用来指导使用rTMS进行认知康复干预的方案的制定。为了实现这些目标，将招募患有帕金森病的退伍军人，并将使用神经心理学测试来表征认知行为。行为的潜在神经生物学将使用先进的功能磁共振成像(FMRI)技术和rsFC分析来表征。将采取多种方法进行功能连通性分析。具体地说，将确定认知网络内或认知网络之间与认知障碍相关的区域的功能连接中断。这些大脑和行为特征将被集体评估，以制定rTMS方案，从而确定皮质刺激部位和刺激参数。将进行一项试点随机对照试验，以确定rTMS改善认知功能的安全性、可行性和有效性。参赛者将接受主动或 在两周的过程中，每天进行10次假rTMS。预计这一创新项目将为我们的基础知识贡献一个缺失的基本元素，如果没有这些元素，就无法理解患有帕金森病的退伍军人的轻度认知障碍。这些知识的获得对于发展和优化PD-MCI退伍军人的认知康复治疗至关重要，最终目标是提高生活质量。与CDA2提案相关的发现可能会为神经康复提供有关MCI和痴呆发生的其他情况的信息。

项目成果

Brain Gaming: A User's Product Guide for the Clinician.

• DOI: 10.1016/j.apmr.2016.03.001
• 发表时间: 2016-08-01
• 期刊: Archives of physical medicine and rehabilitation
• 影响因子: 4.3
• 作者: Kletzel, Sandra L;Cary, Michael P Jr;Heyn, Patricia C
• 通讯作者: Heyn, Patricia C

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury.

• DOI: 10.1097/htr.0000000000000636
• 发表时间: 2020-11
• 期刊: The Journal of head trauma rehabilitation
• 作者: Kletzel SL;Aaronson AL;Guernon A;Carbone C;Chaudhry N;Walsh E;Conneely M;Patil V;Roth E;Steiner M;Pacheco M;Rosenow J;Bender Pape TL
• 通讯作者: Bender Pape TL