The study included a 6-week tACS intervention phase (5 days on and 2 days off for weekends) and another 12-week efficacy/safety assessment phase without tACS intervention (figure 1A). Bilateral tACS over temporal lobes (located by 10–20 electroencephalogram system) was delivered through saline-soaked sponges (sized 4×4 cm²) using a stimulator (Transcranial, London, UK). The 40 Hz sinusoidal current was applied at 2 mA with a duration of 20 min. Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Cognitive Component Assessment (ADAS-Cog) were used for cognition evaluation before (0 week), at the end of (6 weeks) and 12 weeks (end +12 weeks) after the end of the stimulation. Serum A-beta levels were measured with ELISA.

Background Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer’s disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial direct current stimulation (tDCS) in patients still need to be evaluated. Aims This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity. Methods 124 patients with AD were randomly assigned to active tDCS (n=63) or sham tDCS (n=61). The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks (5 days per week, 2 days off). The Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) were used for cognition evaluation at baseline, week 2 and week 6. The cortical plasticity was represented by motor-evoked potential (MEP) measured with an electromyogram. Results The results showed that multiple courses of active tDCS can improve the cognitive functions of patients with AD, especially in the memory domain (word recall, recall of test instructions and word recognition). In addition, the damaged MEP level was enhanced following active treatment. In the active tDCS group, the improvements in ADAS-Cog total and subitem (word recall and word recognition) scores were negatively correlated with the enhancement of MEP. Conclusions Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity, which warrants mechanistic investigations of the relationship between cognition and plasticity in the future. Trial registration number ChiCTR1900021067.