Transcranial direct current stimulation in typical and atypical Alzheimer's disease

经颅直流电刺激治疗典型和非典型阿尔茨海默病

• 批准号: 10447136
• 负责人: Kyrana Tsapkini
• 金额: $ 75.31万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10447136
• 关键词: Affect; Aftercare; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Amnesia; Anodes; Anomia; Aphasia; Area; Atrophic; Auditory; Behavior Therapy; Biological Markers; Brain; Brain region; Caregivers; Categories; Characteristics; Clinical Trials; Cognition; Cognitive; Complex; Controlled Clinical Trials; Coupling; Development; Diffusion Magnetic Resonance Imaging; Disease; Double-Blind Method; Elderly; Electrical Stimulation of the Brain; Evaluation; Event; Failure; Foundations; Functional Magnetic Resonance Imaging; Future; Health system; Hippocampus (Brain); Image; Impaired cognition; Individual; Inferior frontal gyrus; Intervention; Language; Language Development; Language Disorders; Learning; Left; Magnetic Resonance Spectroscopy; Measures; Membrane Potentials; Memory; Methodology; Multi-Institutional Clinical Trial; Names; Nerve Degeneration; Neurocognitive; Neurodegenerative Disorders; Neurons; Neurotransmitters; Oral; Painless; Parahippocampal Gyrus; Patients; Pattern; Performance; Persons; Pharmaceutical Preparations; Phenotype; Physiological; Prefrontal Cortex; Prevalence; Primary Progressive Aphasia; Publishing; Quality of life; Questionnaires; Randomized Controlled Clinical Trials; Rest; Semantics; Site; Sleep; Sum; Symptoms; Synapses; Synaptic Transmission; Syndrome; Techniques; Testing; Therapeutic; Therapeutic Effect; Training; Variant; Verbal Learning; actigraphy; alternative treatment; angular gyrus; base; cingulate cortex; classical conditioning; cognitive function; cognitive task; effective therapy; gamma-Aminobutyric Acid; improved; learning outcome; lexical retrieval; neurological rehabilitation; neuroregulation; post intervention; prevent; relating to nervous system; statistics; theories; treatment effect

Alzheimer’s disease (AD) is the leading neurodegenerative disease of aging with devasting effects on all cognitive functions of patients and a great toll on caregivers and the health system. Given the recent failures of disease-modifying drugs, the current focus is in preventing or mitigating synaptic damage that correlates with cognitive decline in AD patients. Transcranial Direct Current Stimulation (tDCS) is a safe, non-invasive, non- painful electrical stimulation of the brain that is shown to act as a primer at the synaptic level when administered along with behavioral therapy, mostly involving language, learning and memory. Previous studies have shown that tDCS over the left angular gyrus (AG) improves language associative learning in the elderly through changes in functional connectivity between the AG and the hippocampus. Our previous, double-blind, sham controlled, clinical trial on the effects of tDCS in neurodegenerative disorders has also shown augmented effects of lexical retrieval for tDCS. With regard to the mechanisms of tDCS effects in the brain, tDCS modulates the functional connectivity between the stimulated area and other task-related areas, as well as the inhibitory neurotransmitter GABA. In the present study we will compare the effects of active vs. sham tDCS over the AG—an area that is part of the default mode network (DMN) but also a language area, particularly important for semantic integration and event processing—in two predominant AD variants: probable AD with amnesic phenotype and probable AD with non-amnesic (language deficit) phenotype also described as logopenic variant PPA with AD pathology (aphasic AD). We aim to: (1) determine whether active high-definition tDCS (HD-tDCS) targeting the left AG combined with a Word-List Learning Intervention (WordLLI) will improve verbal learning; (2) identify the changes in functional connectivity between the stimulated area (AG) and other structurally and functionally connected areas using resting-state functional magnetic resonance imaging (rsfMRI), i.e., areas of the default mode network (DMN); (3) identify changes in the inhibitory neurotransmitter GABA at the stimulation site and magnetic resonance spectroscopy (MRS). Furthermore, in order to determine whether the new neuromodulatory approaches are effective in alleviating AD symptoms, we need to determine the characteristics of the people that benefit from it. For this reason, to identify responders, we will evaluate neural (functional and structural connectivity), cognitive (memory, executive and language) functions, and physiological characteristics such as sleep, and we will analyze their moderating effects on verbal learning outcomes. A complementary group of experts in neurorehabilitation, clinical trials methodology, imaging methodology and statistics (rsfMRI and MRS) and sleep who have already published together will be collaborating in this comprehensive study. Study results can help: (i) optimize future intervention in individuals with neurodegenerative disorders by providing treatment alternatives; and (ii) provide better understanding of the therapeutic and neuromodulatory effects of tDCS in AD, to impede neurodegeneration and improve patients' and caregivers’ quality of life.

阿尔茨海默病（Alzheimer's disease，AD）是一种主要的神经退行性疾病，对所有人都有毁灭性的影响 患者的认知功能以及护理人员和卫生系统的巨大损失。鉴于最近的失败， 疾病修饰药物，目前的重点是预防或减轻突触损伤， AD患者的认知能力下降。经颅直流电刺激（tDCS）是一种安全、无创、无创的 一种对大脑的疼痛性电刺激，当施用时，其被显示为在突触水平上起引发作用 沿着行为疗法，主要涉及语言、学习和记忆。先前的研究表明 左侧角回（AG）上的tDCS通过改变老年人的语言联想学习， AG和海马体之间的功能连接。我们之前的，双盲，假对照， 关于tDCS在神经退行性疾病中的作用的临床试验也显示了词汇的增强作用。 检索tDCS。关于tDCS在脑中的作用机制，tDCS调节脑组织的功能， 受刺激区域和其他任务相关区域之间的连接，以及抑制性神经递质 GABA在本研究中，我们将比较活性与假tDCS在AG区域的作用， 默认模式网络（DMN）的一部分，也是一个语言区域，对语义集成特别重要 和事件处理-在两种主要的AD变体中：可能的AD与遗忘表型和可能的AD 具有非遗忘症（语言缺陷）表型，也被描述为AD病理学的逻辑缺失变体PPA （失语性AD）。我们的目标是：（1）确定是否主动高清tDCS（HD-tDCS）针对左AG 结合单词列表学习干预（WordLLI）将改善语言学习;（2）识别变化 刺激区（AG）与其他结构和功能连接的区域之间的功能连接 使用静息态功能性磁共振成像（rsfMRI），即，默认模式网络的区域 (DMN)（3）确定刺激部位和磁刺激部位抑制性神经递质GABA的变化; 共振波谱（MRS）。此外，为了确定新的神经调节因子是否 方法在缓解AD症状方面有效，我们需要确定 因此，为了识别应答者，我们将评估神经（功能和结构） 连接），认知（记忆，执行和语言）功能，以及生理特征，如 睡眠，我们将分析它们对语言学习结果的调节作用。一组互补的 神经康复、临床试验方法学、成像方法学和统计学（rsfMRI和MRS）专家 和sleep已经共同发表的文章将在这项综合研究中合作。研究结果 可以帮助：（i）通过提供治疗，优化未来对神经退行性疾病患者的干预 替代品;和（ii）提供更好地理解tDCS在AD中的治疗和神经调节作用， 以阻止神经退化并改善患者和护理人员的生活质量。