Background Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI. Methods 24 older adults with amnestic MCI (aMCI) due to possible Alzheimer’s disease enrolled in a phase I trial of open-label accelerated iTBS to the left dorsolateral prefrontal cortex (8 stimulation sessions of 600 pulses of iTBS/day for 3 days). Participants rated common side effects during and after each session and retrospectively (at post-treatment and 4-week follow-up). They completed brain MRI (for safety assessments and electric field modeling), neuropsychiatric evaluations, and neuropsychological testing before and after treatment; a subset of measures was administered at follow-up. Results Retention was high (95%) and there were no adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participants reported high acceptability, minimal side effects, and low desire to quit despite some rating the treatment as tiring. Electric field modeling data suggest that all participants received safe and therapeutic cortical stimulation intensities. We observed a significant, large effect size (d=0.98) improvement in fluid cognition using the NIH Toolbox Cognition Battery from pre-treatment to post-treatment. Conclusions Our findings support the safety, feasibility, and acceptability of accelerated iTBS in aMCI. In addition, we provide evidence of target engagement in the form of improved cognition following treatment. These promising results directly inform future trials aimed at optimizing treatment parameters. Trial registration number [NCT04503096][1]. No data are available. The data used in this study are not publicly available as they contain confidential clinical information and participants were not asked to consent to data sharing. Analysis code for this study may be requested from the corresponding author. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04503096&atom=%2Fjnnp%2Fearly%2F2024%2F05%2F06%2Fjnnp-2023-332680.atom

中文翻译：

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加速间歇性 theta 爆发 rTMS 治疗遗忘性 MCI 的 I 期试验

背景 新出现的证据表明，重复经颅磁刺激 (rTMS) 可增强轻度认知障碍 (MCI) 的认知能力。加速间歇 theta 爆发刺激 (iTBS) rTMS 方案很有前景，因为它们通过缩短治疗过程而大大减轻负担，但 iTBS 的安全性、可行性和可接受性尚未在 MCI 中建立。方法 24 名因可能患有阿尔茨海默病而患有遗忘性 MCI (aMCI) 的老年人参加了对左背外侧前额叶皮层进行开放标签加速 iTBS 的 I 期试验（8 次刺激，每天 600 个 iTBS 脉冲，持续 3 天）。参与者对每次治疗期间和治疗后以及回顾性（治疗后和 4 周随访时）的常见副作用进行评分。他们在治疗前后完成了脑部MRI（用于安全评估和电场建模）、神经精神评估和神经心理学测试；后续实施了一部分措施。结果 保留率很高（95%），并且治疗没有对神经放射学、神经精神或神经认知产生不良影响。尽管有些人认为治疗很累，但参与者表示可接受性高，副作用最小，戒烟意愿低。电场建模数据表明所有参与者都接受了安全且具有治疗作用的皮质刺激强度。我们观察到使用 NIH Toolbox Cognition Battery 从治疗前到治疗后液体认知有显着的大效应 (d=0.98) 改善。结论 我们的研究结果支持 aMCI 中加速 iTBS 的安全性、可行性和可接受性。此外，我们以治疗后认知改善的形式提供目标参与的证据。这些有希望的结果直接为未来旨在优化治疗参数的试验提供信息。试用注册号[NCT04503096][1]。无可用数据。本研究中使用的数据不公开，因为它们包含机密的临床信息，并且未要求参与者同意数据共享。本研究的分析代码可向通讯作者索取。 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04503096&atom=%2Fjnnp%2Fearly%2F2024%2F05%2F06%2Fjnnp-2023-332680.atom