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

阿尔茨海默病(AD)是一种主要的神经退行性疾病，对所有人都有破坏性影响 患者的认知功能和照顾者和卫生系统的巨大损失。考虑到最近的失败 疾病修饰药物，目前的重点是预防或减轻与以下相关的突触损伤 阿尔茨海默病患者认知功能下降。经颅直流电刺激(Tdcs)是一种安全、无创、无创的治疗方法。 对大脑进行的痛苦的电刺激，被证明在实施时在突触水平起到引爆剂的作用 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 在AG和海马体之间的功能连接上。我们之前的，双盲，假控制， 关于tdcs治疗神经退行性疾病的临床试验也显示词汇的增强作用。 检索tdcs。关于tdcs在大脑中的作用机制，tdcs调节 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接 GABA。在目前的研究中，我们将比较活动和假TDC对AG的影响-这是一个区域 默认模式网络(DMN)的一部分，也是语言领域，对于语义整合尤为重要 和事件处理-在两个主要的AD变体中：可能的AD伴健忘症表型和可能的AD 非健忘症(语言障碍)表型也被描述为伴有AD病理的对数变异PPA (失语症AD)。我们的目标是：(1)确定激活的高清晰度tDCs(HD-tDCs)是否针对左侧AG 结合词表学习干预(WordLLI)将改善词汇学习；(2)确定变化 在刺激区(AG)和其他结构和功能连接的 使用静息状态功能磁共振成像(RsfMRI)的区域，即默认模式网络的区域 (3)确定刺激部位抑制性神经递质GABA的变化和磁 共振光谱学(MRS)。此外，为了确定新的神经调节剂是否 方法是有效的缓解AD症状，我们需要确定的人的特征， 从中受益。因此，为了确定响应者，我们将评估神经(功能和结构 连通性)、认知(记忆、执行和语言)功能以及生理特征，例如 睡眠，我们将分析它们对言语学习结果的调节作用。互补的一组 神经康复、临床试验方法学、成像方法学和统计学专家(rsfMRI和MRS) 已经在一起发表的睡眠研究将在这项全面的研究中展开合作。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 替代方案；和(Ii)更好地了解tdcs在AD中的治疗和神经调节作用， 以阻止神经退行性变，提高患者和照顾者的生活质量。

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.