重复经颅磁刺激(rTMS)正在成为对抗阿尔茨海默病的一种非侵入性治疗策略。阿尔茨海默病患者主要表现出默认模式网络的改变,而前突是关键节点。这里,我们假设TMS靶向前突是减缓阿尔茨海默病患者认知和功能下降的有前景的策略.我们做了一个随机的,双盲,假控制,2期,24周试验,以确定前肌刺激对轻度至中度阿尔茨海默病患者的安全性和有效性。50名阿尔茨海默病患者以1:1的比例随机分配接受precuneus或假rTMS(平均年龄73.7岁;52%为女性)。该试验包括24周的治疗,为期2周的强化课程,其中rTMS(或假)每天应用五次,随后是为期22周的维持期,其中每周施加一次刺激。选择临床痴呆评定量表-方框总和作为主要结果指标,其中将治疗后评分与基线进行比较.次要结局包括阿尔茨海默病评估量表-认知子量表的得分变化,简易精神状态检查与阿尔茨海默病合作研究-日常生活活动量表。此外,单脉冲TMS结合EEG用于评估前皮质皮质兴奋性和振荡活动的神经生理学变化。我们的发现表明,接受前肌重复磁刺激的患者表现出临床痴呆评定量表-方框和评分的稳定表现,而接受假手术治疗的患者评分恶化。与假刺激相比,前肌刺激组的患者在次要结局指标方面也表现出明显更好的表现,包括阿尔茨海默病评估量表-认知子量表,简易精神状态检查与阿尔茨海默病合作研究-日常生活活动量表。神经生理学结果显示,前脑刺激组24周后,前脑皮质兴奋性保持不变,而在假手术组显著降低。最后,我们发现,在前叶刺激治疗组,局部γ振荡增强,但在假手术治疗组没有.我们得出的结论是,24周前叶rTMS可能会减缓阿尔茨海默病的认知和功能下降。针对默认模式网络的重复TMS可以代表阿尔茨海默病患者的一种新的治疗方法。
Repetitive transcranial magnetic stimulation (rTMS) is emerging as a non-invasive therapeutic strategy in the battle against Alzheimer\'s disease. Alzheimer\'s disease patients primarily show alterations of the default mode network for which the precuneus is a key node. Here, we hypothesized that targeting the precuneus with TMS represents a promising strategy to slow down cognitive and functional decline in Alzheimer\'s disease patients. We performed a randomized, double-blind, sham-controlled, phase 2, 24-week
trial to determine the safety and efficacy of
precuneus stimulation in patients with mild-to-moderate Alzheimer\'s disease. Fifty Alzheimer\'s disease patients were randomly assigned in a 1:1 ratio to either receive precuneus or sham rTMS (mean age 73.7 years; 52% female). The
trial included a 24-week treatment, with a 2-week intensive course in which rTMS (or sham) was applied daily five times per week, followed by a 22-week maintenance phase in which stimulation was applied once weekly. The Clinical Dementia Rating Scale-Sum of Boxes was selected as the primary outcome measure, in which post-treatment scores were compared to baseline. Secondary outcomes included score changes in the Alzheimer\'s Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer\'s Disease Cooperative
Study-Activities of Daily Living scale. Moreover, single-pulse TMS in combination with EEG was used to assess neurophysiological changes in precuneus cortical excitability and oscillatory activity. Our findings show that patients that received precuneus repetitive magnetic stimulation presented a stable performance of the Clinical Dementia Rating Scale-Sum of Boxes score, whereas patients treated with sham showed a worsening of their score. Compared with the sham stimulation, patients in the precuneus stimulation group also showed also significantly better performances for the secondary outcome measures, including the Alzheimer\'s Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer\'s Disease Cooperative
Study-Activities of Daily Living scale. Neurophysiological results showed that precuneus cortical excitability remained unchanged after 24 weeks in the precuneus stimulation group, whereas it was significantly reduced in the sham group. Finally, we found an enhancement of local gamma oscillations in the group treated with precuneus stimulation but not in patients treated with sham. We conclude that 24 weeks of precuneus rTMS may slow down cognitive and functional decline in Alzheimer\'s disease. Repetitive TMS targeting the default mode network could represent a novel therapeutic approach in Alzheimer\'s disease patients.