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（由申请人提供）：该提案的目标是增进我们对轻度认知障碍（MCI）的神经生物学基础的理解，该障碍可能导致进行性年龄相关性痴呆，例如阿尔茨海默氏病（AD），并开发一种可靠的检测方法继续发展 AD 的 MCI 患者的早期检测和纵向评估表明，有证据表明大脑皮层中淀粉样蛋白 (Aβ) 的积累不断增加，我们发现 Aβ 毒性会直接损害可塑性机制。我们将评估 MCI 个体的皮质可塑性机制，并将其与现有的完整健康对照组进行比较，以对 MCI 进行分类。将通过评估特定的重复经颅磁刺激 (TMS) 方案（称为 theta 爆发刺激）诱导的皮质反应性调节来探索皮质可塑性的机制。 (TBS)。TBS 前后单脉冲 TMS 引起的运动反应的比较提供了人类大脑可塑性的非侵入性测量，学习和记忆任务将用于证明这种测量的行为相关性。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证据，我们预计这项研究的数据将满足对快速、无创、可靠、可重复和安全的方法的重要需求，以直接评估其功效。神经可塑性机制如果成功，基于 TMS 的皮质反应性和可塑性测量将为 MCI 的病理生理变化提供客观评估，并可作为评估 MCI 认知功能障碍的可翻译生物标志物，为有效疗法的开发提供信息并评估未来的治疗反应。临床试验。