Promoting adaptive neuroplasticity in mild cognitive impairment

促进轻度认知障碍的适应性神经可塑性

• 批准号: 8679447
• 负责人: Benjamin Michael Hampstead
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8679447
• 关键词: Adverse effects; Affect; Age; Aging; Alzheimer' s Disease; Anterior; Basic Science; Behavioral; Brain; Brain region; Caregivers; Characteristics; Cognition; Cognitive; Data; Data Set; Dementia; Diagnosis; Double-Blind Method; Electrical Stimulation of the Brain; Etiology; Face; Functional Magnetic Resonance Imaging; Funding; General Population; Healthcare; Healthcare Systems; Impaired cognition; Incidence; Individual; Institutionalization; Intervention; K-Series Research Career Programs; Laboratories; Learning; Left; Life; Location; MRI Scans; Measures; Mediating; Memory; Memory impairment; Motor; Names; Neuronal Plasticity; Neurosciences Research; Outcome Measure; Participant; Patient Self-Report; Patient risk; Patients; Pattern; Play; Population; Prefrontal Cortex; Quality of life; Questionnaires; Randomized; Randomized Controlled Trials; Relative (related person); Research Infrastructure; Resources; Risk; Role; Series; Short-Term Memory; Staging; Structure; Techniques; Testing; Training; Training Technics; Translating; Veterans; Vietnam; Work; aging population; base; burnout; cognitive process; cognitive rehabilitation; follow-up; functional disability; human old age (65+); improved; memory encoding; memory process; mild cognitive impairment; neural correlate; neuromechanism; neuronal excitability; neuroregulation; novel; public health relevance; semantic processing; stroke rehabilitation; tool

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.

描述（由申请人提供）： 美国人口老龄化可能会压垮我们的医疗基础设施，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内将增加两倍。这个问题在 VA 医疗系统中更为复杂，该系统中超过 40% 的退伍军人年龄在 65 岁或以上，而普通人群中这一比例为 13%。记忆缺陷是 AD 的特征，会导致功能障碍、生活质量下降、护理人员倦怠加剧，并最终导致住院。轻度认知障碍 (MCI) 的诊断可识别那些有记忆缺陷但在日常生活中保持相对独立的人。由于这些患者转变为 AD 的风险大大增加，MCI 提供了一个窗口，在此窗口内进行干预可以最大限度地提高记忆功能并延长独立性。拟议的研究特别关注记忆策略训练和非侵入性大脑刺激的突破性组合。 助记策略是帮助患者解决记忆缺陷的认知“工具”。我们的初步数据表明，助记策略对于提高记忆力是有效的，但（1）并非所有患者都能从训练中受益，（2）患者很难将其概括为新信息。我们在这些早期研究中使用功能磁共振成像（fMRI）来识别策略使用的神经相关性，这表明左腹外侧前额叶皮层就是其中之一 重要区域。经颅直流电刺激 (tDCS) 是一种非侵入性脑刺激，用于增强神经可塑性并提高行为训练技术（例如中风后运动康复）的效果。因此，本研究的中心前提是 tDCS 可以增强腹外侧前额叶皮层的功能，从而诱导适应性神经塑性变化并提高 MCI 患者记忆策略训练的效果。 在这项随机、双盲研究中，参与者将完成 5 个连续治疗疗程，其中他们在目标大脑区域接受主动或假 tDCS 结合助记策略训练。患者将接受基于实验室和现实世界的记忆测试，以检查策略泛化以及训练前后的功能磁共振成像扫描。记忆测试的持久性和功能磁共振成像的改善将在 3 个月的随访中进行检查。功能磁共振成像的使用将提供有关作用机制的关键信息，特别是目标大脑区域 (vlPFC) 是否确实介导行为改善。 预计，相对于假手术组，活跃的 tDCS 组将表现出基于生态的记忆测量的持续改善以及腹外侧前额叶皮层内的激活增加。我们还将研究大脑激活增加与对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。这项史无前例的研究有可能将更多的“基础”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。