Non-Invasive Home Neurostimulation for Mild to Moderate Alzheimer's Disease: Double-Blind, Sham Controlled Randomized Clinical Trial

摘要 阿尔茨海默病的日益流行加上缺乏有效的治疗方案 需要开发用于阿尔茨海默病的新治疗方法，特别是 在医学脆弱人群中造成不良反应风险最小的药物。风险最小，无 侵入性神经调节疗法，如经颅直流电刺激（tDCS），可以缓解 症状和增强功能的老年人与不同的条件。我们在家里开发了一种 tDCS，并证明了这种方法的可行性，并在一项试点研究中进行的患者， 早期阿尔茨海默病，在家里tDCS改善认知能力以及大脑的稳定性 新陈代谢. 我们现建议在先导研究的基础上进一步发展和扩展这项研究，以测试家居式tDCS的临床成效 采用严格的双盲随机临床试验设计，在100例轻度至中度 阿尔茨海默病患者将随机接受tDCS治疗，每周5天，持续6个月 在家或以相同频率进行假治疗。所有参与者将接受认知评估 在基线、干预后以及干预后1个月和3个月， 记录效果的持久性。我们的主要结果是认知表现的变化（由 阿尔茨海默病评估量表-认知子量表测试）。次要结局包括 情绪、生活质量和患者对器械和手术的满意度指标。 还将在基线、干预后， 以及干预后三个月。 我们预测，活跃的tDCS将导致更好的认知表现和更高的生活质量， 与假手术相比，这将是一种令患者及其家属满意的治疗方法。我们 我还假设活性tDCS产生的临床反应将与改善的 功能和结构的连接和使用的背外侧前额叶皮层和相关的 网络（例如执行控制/显著性网络）。 拟议的研究对PAR-19 - 298反应非常积极，该研究征求申请，以建立初步的 神经刺激/神经调节治疗阿尔茨海默病及相关疾病的疗效 痴呆我们提出的临床试验将提供高质量的证据， tDCS在阿尔茨海默病治疗中的应用如果疗效得到证实，这种非侵入性，非- 药物干预可能成为痴呆症护理的重要组成部分。

Abstract The growing prevalence of Alzheimer’s Disease coupled with a dearth of effective treatment options necessitates the development of novel treatment approaches for Alzheimer’s Disease, particularly those that pose minimal risk of adverse effects in a medically fragile population. Minimal risk, non- invasive neuromodulatory therapies, such as transcranial direct current stimulation (tDCS), may relieve symptoms and enhance function in older adults with diverse conditions. We developed an at home tDCS and demonstrated the feasibility of this approach, and in a pilot study conducted in patients with early Alzheimer’s disease, at home tDCS improved cognitive performance as well as stability in brain metabolism. We now propose to build and expand on the pilot study to test the clinical efficacy of home based tDCS using a rigorous double blind randomized clinical trial design in 100 patients with mild to moderate Alzheimer’s disease who will be randomized to receive either tDCS five days per week for six months at home or to sham treatment at the same frequency. All participants will receive cognitive assessments at baseline, post-intervention, and at one month and three months after intervention to explore and document durability of effects. Our primary outcome is change in cognitive performance (assessed by the Alzheimer's Disease Assessment Scale - Cognitive subscale test). Secondary outcomes include measures of mood, quality of life, and patient satisfaction with both the device and procedure. Neuroimaging markers of potential neuroplasticity will also be evaluated at baseline, post-intervention, and at three months post-intervention. We predict that the active tDCS will result in better cognitive performance, and higher quality of life, as compared to sham, and will be a satisfactory treatment approach for patients and their families. We also hypothesize that the clinical response produced by active tDCS will be associated with improved functional and structural connectivity and use of the Dorsolateral Prefrontal Cortex and associated networks (e.g. executive control/salience networks). The proposed study is highly responsive to PAR-19-298, which solicits applications to establish initial efficacy of neurostimulation/neuromodulation in the treatment of Alzheimer’s disease and related dementia. Our proposed clinical trial will provide high-quality evidence about the efficacy of at-home tDCS in the treatment of Alzheimer’s Disease. If efficacy is demonstrated, this non-invasive, non- pharmacologic intervention may become an important part of dementia care.