Zhang Yushu, Dong Ke, Yang Jiajia, Guo Qifan, Zhao Yan, Zhu Xiaoxia, Liu Dongxu, Liu Peng
Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Clinical Research Center for Rehabilitation Medicine, Sun Yat-sen University, Guangzhou, China.
Front Aging Neurosci. 2025 Apr 22;17:1536573. doi: 10.3389/fnagi.2025.1536573. eCollection 2025.
Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising non-invasive intervention for Alzheimer's disease (AD), yet therapeutic outcomes remain inconsistent across studies. This meta-analysis aimed to evaluate the cognitive benefits of rTMS in AD patients, with a specific focus on stimulation targets and protocols variations.
A systematic literature search was conducted in PubMed, Web of Science, Embase, and Cochrane Library for relevant English-language studies published up to 31 May 2024. Cognitive outcomes were assessed using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-Cog). Data were pooled using a random-effects model, with standardized mean difference (SMD) or mean differences (MD) and 95% confidence intervals (CI) calculated. Subgroup analyses were performed to examine the effects of stimulation targets, protocol variations and population demographics on rTMS efficacy.
Twenty-two studies involving 874 participants were included in this meta-analysis. Overall, rTMS significantly improved cognitive function (SMD = 0.27; 95% CI = 0.14-0.41; < 0.0001), showing that the efficacy of rTMS varied by stimulation target and protocol. Stimulation of the dorsolateral prefrontal cortex (DLPFC) led to significant cognitive improvement (SMD = 0.49, 95% CI = -0.26 to 0.73; < 0.0001), whereas bilateral DLPFC stimulation showed no significant improvement (SMD = 0.13; 95% CI = -0.40 to 0.66; = 0.62). Stimulating the parietal lobe or associated regions produced moderate cognitive benefits (SMD = 0.29; 95% CI = 0.03-0.55; = 0.03). Notably, multi-target stimulation over the bilateral DLPFC, parietal lobes, Wernicke's area, and Broca's area also showed substantial cognitive improvement (MD = 2.85; 95% CI = 1.69-4.00; < 0.00001). Additionally, subgroup analysis based on geographical background revealed greater effects in studies conducted in Asia (SMD = 0.40, 95% CI = 0.14-0.65; < 0.003).
rTMS is an effective intervention for cognitive enhancement in AD, with its efficacy significantly influenced by stimulation target and protocol. Notably, the greater cognitive benefits observed in Asian populations suggest a potential role of genetic and demographic factors that warrant further investigation. These findings contribute to the development of optimized, personalized rTMS protocols for AD treatment.
https://www.crd.york.ac.uk/PROSPERO/recorddashboard, CRD42023434084.
重复经颅磁刺激（rTMS）正逐渐成为一种有前景的针对阿尔茨海默病（AD）的非侵入性干预手段，但各研究的治疗效果仍不一致。本荟萃分析旨在评估rTMS对AD患者认知功能的益处，特别关注刺激靶点和方案差异。
在PubMed、Web of Science、Embase和Cochrane图书馆中进行系统的文献检索，以查找截至2024年5月31日发表的相关英文研究。使用简易精神状态检查表（MMSE）和阿尔茨海默病评估量表认知部分（ADAS-Cog）评估认知结果。采用随机效应模型合并数据，计算标准化平均差（SMD）或平均差（MD）及95%置信区间（CI）。进行亚组分析以检验刺激靶点、方案差异和人群人口统计学特征对rTMS疗效的影响。
本荟萃分析纳入了22项研究，共874名参与者。总体而言，rTMS显著改善了认知功能（SMD = 0.27；95% CI = 0.14 - 0.41；P < 0.0001），表明rTMS的疗效因刺激靶点和方案而异。刺激背外侧前额叶皮质（DLPFC）导致显著的认知改善（SMD = 0.49，95% CI = -0.26至0.73；P < 0.0001），而双侧DLPFC刺激未显示出显著改善（SMD = 0.13；95% CI = -0.40至0.66；P = 0.62）。刺激顶叶或相关区域产生了中等程度的认知益处（SMD = 0.29；95% CI = 0.03 - 0.55；P = 0.03）。值得注意的是，双侧DLPFC、顶叶、韦尼克区和布洛卡区的多靶点刺激也显示出显著的认知改善（MD = 2.85；95% CI = 1.69 - 4.00；P < 0.00001）。此外，基于地理背景的亚组分析显示，在亚洲进行的研究中效果更明显（SMD = 0.40，95% CI = 0.14 - 0.65；P < 0.003）。
rTMS是一种有效的AD认知增强干预手段，其疗效受刺激靶点和方案的显著影响。值得注意的是，在亚洲人群中观察到的更大认知益处表明遗传和人口统计学因素可能发挥作用，值得进一步研究。这些发现有助于为AD治疗开发优化的、个性化的rTMS方案。
https://www.crd.york.ac.uk/PROSPERO/recorddashboard，CRD42023434084。
