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

作者：Qian Gong, Xuemin Fu, Daxi Feng, Shuying Rao, Benno Pütz, Bertram Müller‐Myhsok, Lili Wei, Chanchan Shen, Yingchun Zhang, Luoyi Xu, Wenjuan Chen, Wenjuan Chen, Kehua Yang, Dandan Chen, Xinghui Lv, Z. Yan, Dandan Luo, Pengfei Wei, Haiteng Jiang, Wei Chen, Wei Chen · 发表于：Translational Psychiatry · 年份：2026 · DOI：10.1038/s41398-026-03822-z · 研究领域：Transcranial Magnetic Stimulation Studies、Planarian Biology and Electrostimulation、Spatial Neglect and Hemispheric Dysfunction

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 ne...