Brain Plasticity Measures in MCI

 描述(申请人提供)：这项建议的目的是促进我们对可能导致进行性年龄相关痴呆(如阿尔茨海默病(AD))的轻度认知障碍(MCI)的神经生物学基础的了解，并开发一种可靠的检测方法，用于早期发现和纵向评估。继续发展为阿尔茨海默病的轻度认知障碍患者有证据表明，大脑皮层中淀粉样β蛋白(Aβ)的积聚增加。我们假设，β毒性直接损害可塑性机制，这将通过非侵入性神经生理学方法得到证实，并解释认知功能障碍。我们将评估MCI患者的皮质可塑性机制，并将其与现有的健康对照人群进行比较。正电子发射断层成像将被用来将MCI患者分为Aβ和Aβ-。皮层可塑性的机制将通过评估一种特定的重复性经颅磁刺激(TMS)方案(称为theta Burst刺激(TBS))诱导的皮质反应性的调制来探索。TBS前后单脉冲TMS诱发的运动反应的比较提供了一种无创性的人类大脑可塑性的测量方法。认知测试以及学习和记忆任务将被用来证明这种可塑性测量的行为相关性。我们的初步研究证明了我们方法的可行性，并为我们的假设提供了支持性的证据。我们预计，这项研究的数据将满足对快速、非侵入性、可靠、可重复和安全的方法的重要需求，以直接评估神经再生机制在MCI中的疗效。如果成功，基于TMS的皮质反应性和可塑性的测量将为MCI的病理生理变化提供客观的评估，并可能作为一种可翻译的生物标记物来评估MCI的认知功能障碍，为有效治疗的发展提供信息，并在未来的临床试验中评估治疗反应。

 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.