Brain Plasticity Measures in MCI

MCI 中的大脑可塑性测量

• 批准号: 9276587
• 负责人: Alvaro Pascual-Leone
• 金额: $ 21.63万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2018-12-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276587
• 关键词: Address; Aerobic Exercise; Aftercare; Age; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Auditory; Autistic Disorder; Behavioral; Biological Assay; Biological Markers; Brain; Cell Death; Clinical; Clinical Trials; Cognitive Therapy; Data; Data Set; Dementia; Development; Diagnosis; Disease; Distal; Early Diagnosis; Elderly; Electromagnetics; Etiology; Face; Future; Goals; Hand; Human; Image; Impaired cognition; Impairment; In Vitro; Individual; Injection of therapeutic agent; Lead; Learning; Link; Longevity; Manuscripts; Measures; Mediating; Memory; Methods; Motor; Motor Cortex; Motor Evoked Potentials; Names; Neurobiology; Neuronal Dysfunction; Neuronal Injury; Neuronal Plasticity; Neuropsychological Tests; Participant; Pathogenicity; Patients; Pattern; Pharmaceutical Preparations; Physiologic pulse; Pilot Projects; Population; Positron-Emission Tomography; Process; Protocols documentation; Recruitment Activity; Risk Assessment; Schizophrenia; Severities; Signal Transduction; Subgroup; Surrogate Markers; Synaptic plasticity; Teenagers; Testing; Time; Transcranial magnetic stimulation; Verbal Learning; abeta accumulation; abeta toxicity; age related; amyloid imaging; base; behavioral study; cerebral atrophy; cognitive function; cognitive task; cognitive testing; cognitive training; cohort; computerized; developmental disease; drug development; effective therapy; healthy aging; imaging study; in vivo; insight; lifestyle intervention; mild cognitive impairment; neurophysiology; phase III trial; pre-clinical; predictive of treatment response; prevent; public health relevance; repetitive transcranial magnetic stimulation; response; synaptic function; tau Proteins; treatment response

 DESCRIPTION (provided by applicant): The goal of this proposal is to advance our understanding of the neurobiological substrates of mild cognitive impairment (MCI) that may lead to progressive age-related dementias such as Alzheimer's disease (AD), and develop a reliable assay for their early detection and longitudinal assessment. MCI patients who go on to develop AD show evidence of increasing accumulation of amyloid beta (Aβ) in the brain cortex. We hypothesize that Aβ toxicity directly impairs mechanisms of plasticity that will be demonstrable by a non-invasive neurophysiologic method and account for cognitive dysfunction. We will evaluate mechanisms of cortical plasticity in individuals with MCI and compare them to an existing cohort of intact healthy controls. Positron emission tomography (PET) imaging will be used to classify MCI individuals as Aβ+ and Aβ-. Mechanisms of cortical plasticity will be explored by assessing the modulation of cortical reactivity induced by a specific repetitive transcranial magnetic stimulation (TMS) protocol known as theta burst stimulation (TBS). The comparison of the motor responses induced by single-pulse TMS before and following TBS provides a noninvasive measure of brain plasticity in humans. Cognitive testing and tasks of learning and memory will be used to demonstrate the behavioral correlates of this measure of plasticity. Our pilot studies demonstrate the feasibility of our approach and provide supportive evidence for our hypothesis. We anticipate that data from this study will address an important need for a rapid, noninvasive, reliable, repeatable, and safe method to directly assess the efficacy of neuroplastic mechanisms in MCI. If successful, TMS-based measures of cortical reactivity and plasticity will provide an objective assessment of pathophysiological changes in MCI and may serve as a translatable biomarker to assess cognitive dysfunction in MCI, inform the development of effective therapies and evaluate treatment response in future clinical trials.

 描述（由适用提供）：该提案的目的是促进我们对轻度认知障碍（MCI）神经生物学底物的理解，这可能会导致与年龄相关的痴呆症（例如阿尔茨海默氏病）（AD），并为其早期检测和持续评估而开发可靠的评估。继续开发AD的MCI患者表明，淀粉样蛋白β（Aβ）在脑皮质中的积累增加。我们假设Aβ毒性直接损害了可塑性机制，这将通过非侵入性神经生理学方法证明，并解释了认知功能障碍。我们将评估MCI个体皮质可塑性的机制，并将其与现有的完整健康对照组进行比较。正电子发射断层扫描（PET）成像将用于将MCI个体分类为Aβ+和Aβ-。通过评估特定重复的经颅磁刺激（TMS）方案（称为theta爆发刺激（TBS））引起的皮质反应性的调节，将探索皮质可塑性的机制。 TBS之前和之后由单脉冲TM引起的运动反应的比较提供了对人类脑可塑性的无创测量。认知测试和学习和记忆的任务将用于证明可塑性测量的行为相关性。我们的试点研究证明了我们的方法的可行性，并为我们的假设提供了支持的证据。我们预计这项研究的数据将解决快速，无创，可靠，可重复和安全的方法的重要需求，以直接评估MCI中神经塑性机制的有效性。如果成功，则基于TMS的皮质反应性和可塑性的测量将提供对MCI病理生理变化的客观评估，并且可以作为可翻译的生物标志物，以评估MCI的认知功能障碍，为有效疗法的发展提供了信息，并评估未来临床试验中的治疗反应。