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: 10045358
• 负责人: Kyrana Tsapkini
• 金额: $ 78.14万
• 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/10045358
• 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; Pharmaceutical Preparations; Phenotype; Physiological; Prefrontal Cortex; Prevalence; Primary Progressive Aphasia; Publishing; Quality of life; Questionnaires; Randomized Controlled Clinical Trials; Rest; Semantics; Site; Sleep; Structure; 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 (AD) 是一种主要的衰老神经退行性疾病，对所有人都造成毁灭性影响 患者的认知功能以及对护理人员和卫生系统造成的巨大损失。鉴于最近的失败 缓解疾病的药物，目前的重点是预防或减轻与以下疾病相关的突触损伤 AD患者的认知能力下降。经颅直流电刺激 (tDCS) 是一种安全、非侵入性、非侵入性的治疗方法。 对大脑进行痛苦的电刺激，在施用时可作为突触水平的引物 以及行为疗法，主要涉及语言、学习和记忆。先前的研究表明 左角回 (AG) 上的 tDCS 通过改变改善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 对神经退行性疾病的影响的临床试验也显示了词汇的增强效果 tDCS 检索。关于 tDCS 在大脑中的作用机制，tDCS 调节功能 刺激区域和其他任务相关区域以及抑制性神经递质之间的连接 伽马氨基丁酸。在本研究中，我们将比较主动 tDCS 与假 tDCS 对 AG（AG 区域）的影响。 是默认模式网络 (DMN) 的一部分，也是语言区域，对于语义集成尤其重要 和事件处理——两种主要的 AD 变体：具有遗忘表型的可能 AD 和可能 AD 具有非遗忘（语言缺陷）表型，也被描述为具有 AD 病理学的语言减少变异 PPA （失语症 AD）。我们的目标是：（1）确定主动高清 tDCS（HD-tDCS）是否针对左侧 AG 与单词列表学习干预 (WordLLI) 相结合将改善言语学习； (2) 识别变化 刺激区域 (AG) 与其他结构和功能连接之间的功能连接 使用静息态功能磁共振成像 (rsfMRI) 的区域，即默认模式网络的区域 （DMN）； (3) 识别刺激部位抑制性神经递质 GABA 的变化和磁性 共振光谱（MRS）。此外，为了确定新的神经调节剂是否 方法可以有效缓解 AD 症状，但我们需要确定采取这种方法的人群的特征 从中受益。因此，为了识别响应者，我们将评估神经（功能和结构） 连接性）、认知（记忆、执行和语言）功能以及生理特征，例如 睡眠，我们将分析它们对语言学习结果的调节作用。一个互补的群体 神经康复、临床试验方法、成像方法和统计学（rsfMRI 和 MRS）方面的专家 和睡眠已经一起发表文章的人将在这项综合研究中进行合作。研究结果 可以帮助：（i）通过提供治疗来优化对神经退行性疾病患者的未来干预 替代方案； (ii) 更好地了解 tDCS 在 AD 中的治疗和神经调节作用， 阻止神经退行性变并改善患者和护理人员的生活质量。