Promoting adaptive neuroplasticity in mild cognitive impairment

描述(由申请人提供)： 美国人口老龄化可能会使我们的医疗基础设施不堪重负，特别是考虑到仅阿尔茨海默病(AD)的发病率预计在未来几十年就会增加两倍。这个问题在退伍军人保健系统中变得更加复杂，超过40%的退伍军人年龄在65岁或以上，而普通人口中的这一比例为13%。记忆缺陷是阿尔茨海默病的特征，会导致功能障碍、生活质量下降、照顾者职业倦怠增加，并最终导致制度化。轻度认知障碍(MCI)的诊断是指那些有记忆缺陷但在日常生活中保持相对独立的人。由于这些患者转换为AD的风险大大增加，MCI提供了一个窗口，在此窗口内，干预可以最大限度地发挥记忆功能，延长独立性。这项拟议的研究特别关注记忆策略培训和非侵入性脑刺激的开创性组合。助记策略是一种认知“工具”，可以帮助患者克服记忆缺陷。我们的初步数据表明，助记策略对于改善记忆是有效的，但(1)并不是所有的患者都能从训练中受益，(2)患者很难概括出新的信息。在这些早期的研究中，我们使用功能磁共振成像(Fmri)来确定策略使用的神经关联，这表明左腹外侧前额叶皮质就是其中之一。 重要区域。经颅直流电刺激(TDC)是一种非侵入性脑刺激，用于增强神经可塑性和改善行为训练技术(例如，中风后的运动康复)的疗效。因此，本研究的中心前提是tDCs可以增强MCI患者腹外侧额叶皮质的功能，从而诱导适应性神经可塑性改变，提高记忆策略训练的有效性。在这项随机、双盲的研究中，参与者将完成5个连续的治疗疗程，在这些疗程中，他们在目标大脑区域接受积极或虚假的tDCs，并结合记忆策略训练。患者将在培训前后接受基于实验室和真实世界的记忆测试，以检查策略泛化以及功能磁共振扫描。将在3个月的随访中检查记忆测试的持久性和功能磁共振成像的改善情况。功能磁共振成像的使用将提供有关作用机制的关键信息，特别是靶向大脑区域(VLPFC)是否确实介导了行为改善。预计，与假手术组相比，活跃的tdcs组将在基于生态的记忆测量方面显示出持续的改善，并增加了腹外侧额叶皮质的激活。我们还将研究大脑激活增加与目标大脑区域介导的其他认知过程的普遍影响之间的关系。这项首开先河的研究有可能将更基本的科学发现有意义地转化为针对我们老龄化人口的神经解剖学目标和功能上有意义的治疗方法。

DESCRIPTION (provided by applicant): The aging US population threatens to overwhelm our healthcare infrastructure, especially since the rate of Alzheimer's disease (AD) alone is expected to triple in the coming decades. This problem is compounded in the VA Healthcare System, where over 40 percent of veterans are age 65 or older compared to 13 percent within the general population. Memory deficits are characteristic of AD and cause functional impairment, reduced quality of life, increased caregiver burnout, and eventual institutionalization. The diagnosis of mild cognitive impairment (MCI) identifies those with memory deficits but who remain relatively independent in everyday life. Because these patients are at substantially increased risk of converting to AD, MCI provides a window within which interventions could maximize memory functioning and prolong independence. The proposed study focuses specifically on a groundbreaking combination of mnemonic strategy training and non- invasive brain stimulation. Mnemonic strategies are cognitive "tools" that help patients work around memory deficits. Our preliminary data suggest that mnemonic strategies are effective for improving memory but that (1) not all patients benefit from training and (2) patients have difficulty generalizing them to new information. We have used functional magnetic resonance imaging (fMRI) in these earlier studies to identify the neural correlates of strategy use, which suggest that the left ventrolateral prefrontal cortex is one such vital region. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that is used to enhance neuroplasticity and improve the efficacy of behavioral training techniques (e.g., motor rehabilitation after stroke). Thus, the central premise of the proposed study is that tDCS can enhance functioning in the ventrolateral prefrontal cortex, thereby inducing adaptive neuroplastic change and increasing the efficacy of mnemonic strategy training in patients with MCI. In this randomized, double-blind study, participants will complete 5 consecutive treatment sessions in which they receive either active or sham tDCS over the targeted brain region in combination with mnemonic strategy training. Patients will undergo both laboratory-based and real-world memory testing to examine strategy generalization as well as fMRI scanning before and after training. Persistence of memory test and fMRI improvements will be examined at a 3-month follow-up. The use of fMRI will provide critical information about the mechanisms of action, especially whether the targeted brain region (vlPFC) does, in fact, mediate behavioral improvement. It is expected that, relative to the sham group, the active tDCS group will demonstrate persistent improvement in ecologically-based measures of memory as well as increased activation within the ventrolateral prefrontal cortex. We will also examine the relationship between increased brain activation and generalized effects on other cognitive processes mediated by the targeted brain region. This first-of-its-kind study has the potential to meaningfully translate more "basic" science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.