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: 10260455
• 负责人: Kyrana Tsapkini
• 金额: $ 75.9万
• 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/10260455
• 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.

阿尔茨海默氏病（AD）是衰老的主要神经退行性疾病 患者的认知功能以及护理人员和卫生系统的巨大损失。考虑到最近的失败 疾病改良药物，目前的重点是预防或减轻与 AD患者的认知能力下降。经颅直流刺激（TDC）是一种安全的，无创的，非 - 施用时，大脑的疼痛电刺激被证明是在突触水平上起底漆的痛苦 与行为疗法一起，主要涉及语言，学习和记忆。先前的研究表明 左角回（Ag）上的TDC通过更改改善了语言的关联学习 在AG和海马之间的功能连通性中。我们以前的双盲，假控制， TDC在神经退行性疾病中的影响的临床试验也显示了词汇的增强作用 TDC的检索。关于大脑中TDCS效应的机制，TDCS调节功能 刺激区域与其他任务相关区域以及抑制性神经递质之间的连通性 加巴。在本研究中，我们将比较主动与假TDC对Ag的影响 - 默认模式网络（DMN）的一部分，但也是语言领域，对于语义集成尤其重要 和事件处理 - 在两个主要的AD变体中：有问题的AD与失忆表型和有问题的AD 具有非障碍（语言防御）表型也被描述为具有AD病理学的徽标变体PPA （失语广告）。我们的目的是：（1）确定是否针对左AG的主动高清TDC（HD-TDC）是 结合单词列表​​学习干预（WordLli）将改善言语学习； （2）确定更改 在刺激区域（Ag）和其他结构和功能连接的功能连接中 使用静止状态功能磁共振成像（RSFMRI）的区域，即默认模式网络的区域 （DMN）; （3）确定刺激部位和磁性抑制性神经递质GABA的变化 共振光谱（MRS）。此外，为了确定新神经调节是否 方法可有效缓解AD症状，我们需要确定人们的特征 从中受益。因此，要确定响应者，我们将评估神经（功能和结构性 连接性），认知（记忆，执行和语言）功能以及物理特征（例如 睡眠，我们将分析它们对言语学习成果的调节作用。一组完整的 神经康复，临床试验方法，成像方法和统计学专家（RSFMRI和MRS） 已经一起出版的睡眠将在这项综合研究中进行合作。研究结果 可以提供帮助：（i）通过提供治疗来优化神经退行性疾病患者的未来干预 替代方案； （ii）更好地了解TDC在AD中的治疗和神经调节作用， 阻碍神经变性并改善患者和看护人的生活质量。