High-dose accelerated intermittent theta burst stimulation improves cognitive function in early Alzheimer’s disease: A randomized sham-controlled trial

Abstract Introduction This clinical trial investigates the efficacy and safety of a personalized 15-day accelerated intermittent theta-burst stimulation (aiTBS) protocol, targeted at either the default mode network (DMN) or the fronto-parietal network (FPN), in individuals with mild Alzheimer’s disease (AD). Methods 45 patients with mild AD were randomized 1:1:1 to receive 15 consecutive days of high-dose aiTBS (7200 pulses/day) targeting the DMN or FPN, or sham. The primary outcome was the change in ADAS-Cog after 15 days of treatment. Results Both active aiTBS groups demonstrated significantly greater ADAS-Cog improvement than sham at the primary endpoint. Response rates for a clinically meaningful improvement (≥3-points on ADAS-Cog) were significantly higher in the active groups (DMN: 38%; FPN: 47%) than in the sham group (0%). The improvement in active groups was sustained at 3-month follow-up. Discussion Personalized aiTBS targeting the DMN or FPN produced clinically meaningful cognitive benefits in mild AD and was safe.