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<p>Cognitive deficits are a hallmark of Alzheimer’s disease (AD), and effective treatments remain elusive. Transcranial alternating current stimulation (tACS), a non-invasive technique, has shown potential in improving cognitive function across various populations, but further research is needed to investigate its efficacy in AD. In a randomized, double-blind, sham-controlled pilot trial, 36 mild AD patients received active or sham theta-tACS (8 Hz, 1.6 mA, 20-min daily) during <i>n</i>-back task for two weeks, followed by a 10-week follow-up. Cognitive assessments and resting-state EEG were analyzed at baseline, after-treatment, and follow-up. The results showed that the active group demonstrated significant cognitive improvements after treatment (MMSE: <i>t</i> (15) =-3.273, <i>p</i> = 0.005, Cohen’s <i>d</i> = 0.82), particularly in short-term memory (MMSE-recall: <i>Z</i> = -2.11, <i>p</i> = 0.035, <i>r</i> = 0.53), with maintained benefits after 10 weeks. In contrast, the sham group exhibited long-term cognitive decline (MMSE: <i>t</i> (4) = 3.586, <i>p</i> = 0.023, Cohen’s <i>d</i> = -1.60). EEG analysis revealed reduced gamma power (<i>t</i> (23) = 2.689, <i>p</i> = 0.013, Cohen’s <i>d</i> = 1.077) and theta connectivity in active group, particularly in the frontotemporal regions (F4/F7: <i>t</i> (23) = 2.467, <i>p</i> = 0.021, Cohen’s <i>d</i> = 0.988; F4/T3: <i>t</i> (23) = 2.465, <i>p</i> = 0.022, Cohen’s <i>d</i> = 0.987), which was correlated with cognitive improvements (<i>R</i> = –0.57, <i>p</i> = 0.043). In conclusion, tACS combining cognitive training may offer cognitive benefits in mild AD by modulating neural activity, though further studies are needed to clarify its mechanisms.</p>

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Randomized, double-blind, sham-controlled pilot trial of theta-band transcranial alternating current stimulation during cognitive training in mild Alzheimer’s disease

  • 期刊论文

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  • 发表日期：

    2026年1月31日

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  • Qian Gong,
  • Xuemin Fu,
  • Daxi Feng,
  • Shuying Rao,
  • Benno Pütz,
  • Bertram Müller-Myhsok,
  • Lili Wei,
  • Chanchan Shen,
  • Yingchun Zhang,
  • Luoyi Xu,
  • Wenjuan Chen,
  • Kehua Yang,
  • Dandan Chen,
  • Xinghui Lv,
  • Zhongmei Yan,
  • Dandan Luo,
  • Pengfei Wei,
  • Haiteng Jiang,
  • Wei Chen

摘要

Cognitive deficits are a hallmark of Alzheimer’s disease (AD), and effective treatments remain elusive. Transcranial alternating current stimulation (tACS), a non-invasive technique, has shown potential in improving cognitive function across various populations, but further research is needed to investigate its efficacy in AD. In a randomized, double-blind, sham-controlled pilot trial, 36 mild AD patients received active or sham theta-tACS (8 Hz, 1.6 mA, 20-min daily) during n-back task for two weeks, followed by a 10-week follow-up. Cognitive assessments and resting-state EEG were analyzed at baseline, after-treatment, and follow-up. The results showed that the active group demonstrated significant cognitive improvements after treatment (MMSE: t (15) =-3.273, p = 0.005, Cohen’s d = 0.82), particularly in short-term memory (MMSE-recall: Z = -2.11, p = 0.035, r = 0.53), with maintained benefits after 10 weeks. In contrast, the sham group exhibited long-term cognitive decline (MMSE: t (4) = 3.586, p = 0.023, Cohen’s d = -1.60). EEG analysis revealed reduced gamma power (t (23) = 2.689, p = 0.013, Cohen’s d = 1.077) and theta connectivity in active group, particularly in the frontotemporal regions (F4/F7: t (23) = 2.467, p = 0.021, Cohen’s d = 0.988; F4/T3: t (23) = 2.465, p = 0.022, Cohen’s d = 0.987), which was correlated with cognitive improvements (R = –0.57, p = 0.043). In conclusion, tACS combining cognitive training may offer cognitive benefits in mild AD by modulating neural activity, though further studies are needed to clarify its mechanisms.