High-intensity transcranial alternating current stimulation improves sleep quality in patients with mild Alzheimer's disease: Findings from the TRANSFORM-AD study

Background High-intensity transcranial alternating current stimulation (Hi-tACS) has shown beneficial effects on cognitive function in Alzheimer's disease (AD). However, data on the effects of hi-tACS on sleep quality and emotional state in patients with AD are still limited. Objective This study aimed to investigate the influences of hi-tACS on sleep quality and emotional state in AD. Methods The TRANSFORM-AD study was a double-blind, randomized-controlled trial that enrolled individuals with mild AD. Participants were randomized to receive hi-tACS group or sham stimulation group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 consecutive days. Pittsburgh sleep quality index (PSQI), Hamilton anxiety Rating Scale (HAMA), Hamilton depression Rating Scale (HAMD) and Quality of life in Alzheimer's Disease scale (QOL-AD) were evaluated at baseline, and the end of the intervention. Results Among 43 participants with complete baseline and post-intervention assessments, Hi-tACS reduced post-intervention PSQI scores compared with sham after adjustment for baseline PSQI (adjusted mean difference, −2.34 points; 95% CI, −3.63 to −1.05; p < 0.001). Baseline-adjusted effects for HAMA (−1.43; 95% CI, −2.89 to 0.02), HAMD (0.44; 95% CI, −1.28 to 2.15), and QOL-AD (2.07; 95% CI, −1.57 to 5.70) were imprecise and included the null. Conclusion Hi-tACS improved subjective sleep quality in patients with mild AD. The present secondary analysis did not provide conclusive evidence of effects on anxiety, depression, or quality of life; these exploratory outcomes require confirmation in larger, adequately powered trials. Trial registration: ClinicalTrials.gov, NCT 03920826.