International Centre for Education and Research in Neuropsychiatry, Samara State Medical University, 78 Nagornaya Street, 443016 Samara, Russia,
Psychiatr Danub. 2024 Sep;36(Suppl 2):188-202.
Alzheimer's disease (AD) presents a major global health issue of significant socio-economic impact. Pharmacological treatments for AD have limited efficacy, prompting the exploration of alternative therapies, such as repetitive transcranial magnetic stimulation (rTMS), a promising non-invasive technique to enhance cognitive function in AD patients. Our systematic review and meta-analysis aim to evaluate the efficacy of rTMS in relation to cognitive function in AD patients, identify optimal rTMS stimulation parameters, and understand the underlying neural mechanisms.
We conducted a comprehensive literature search in PubMed using predefined search terms to identify original research articles investigating the effects of rTMS on cognitive function in AD patients. We selected only randomized controlled trials (RCTs) with sufficient quantitative data for comparing active rTMS to the sham-coil treatment, and then performed a random effects meta-analysis using standardized mean differences (SMDs) to synthesize the effects across studies.
The systematic review included 22 studies, among which 14 RCTs met our criteria for meta-analysis. High-frequency rTMS, particularly targeting the dorsolateral prefrontal cortex (DLPFC), evoked significant cognitive improvements in AD patients, with a moderate positive effect size of rTMS on cognitive function (Hedges' g=0.580, 95% CI [0.268, 0.892], p<0.001), albeit with substantial heterogeneity (I=59%). Funnel plot asymmetry and Egger's test suggested a potential publication bias, but fail-safe N analysis indicated a robust finding. Moreover, anhedonia-apathy symptoms and motor-cognitive exercises mediated the efficacy of tTMS in ameliorating cognitive functioning across several studies.
rTMS demonstrates moderate efficacy in improving cognitive function in AD-patients, most distinctly with high-frequency rTMS stimulation protocols targeting the DLPFC area. The meta-analysis support rTMS as a viable therapeutic intervention for cognitive enhancement in AD. Future promising research should focus on personalized treatment strategies targeting mediating factors, baseline connectivity patterns, and TMS-induced neuroplasticity in AD.
阿尔茨海默病（AD）是一个重大的全球性健康问题，具有重大的社会经济影响。AD 的药物治疗疗效有限，促使人们探索替代疗法，如重复经颅磁刺激（rTMS），这是一种有前途的非侵入性技术，可以增强 AD 患者的认知功能。我们的系统评价和荟萃分析旨在评估 rTMS 对 AD 患者认知功能的疗效，确定最佳的 rTMS 刺激参数，并了解其潜在的神经机制。
我们使用预定义的搜索词在 PubMed 上进行了全面的文献检索，以确定研究 rTMS 对 AD 患者认知功能影响的原始研究文章。我们只选择了具有足够定量数据的随机对照试验（RCT），将活性 rTMS 与假线圈治疗进行比较，然后使用标准化均数差（SMD）进行随机效应荟萃分析，以综合研究结果。
系统评价包括 22 项研究，其中 14 项 RCT 符合我们的荟萃分析标准。高频 rTMS，特别是针对背外侧前额叶皮质（DLPFC）的刺激，可显著改善 AD 患者的认知功能，rTMS 对认知功能的影响具有中等强度（Hedges'g=0.580，95%置信区间[0.268,0.892]，p<0.001），但存在很大的异质性（I=59%）。漏斗图不对称和 Egger 检验提示存在潜在的发表偏倚，但失效安全 N 分析表明结果稳健。此外，几项研究表明，快感缺失-淡漠症状和运动认知练习介导了 rTMS 改善认知功能的疗效。
rTMS 在改善 AD 患者的认知功能方面具有中等疗效，最明显的是针对 DLPFC 区域的高频 rTMS 刺激方案。荟萃分析支持 rTMS 作为 AD 认知增强的一种可行的治疗干预措施。未来有前途的研究应集中在针对中介因素、基线连接模式和 AD 中 TMS 诱导的神经可塑性的个性化治疗策略上。
