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

Xu, N.; Xing, Y.; Li, A.; Pan, R.; Liu, S.; Gao, J.; Liu, X.; Tao, T.; Zhang, P.; Xie, W.; Guo, N.; Chen, Y.; Sun, X.; Wu, J.; Gong, W.; Liu, H.; Tang, Y.; Wang, D.

2026-02-16 geriatric medicine
10.64898/2026.02.13.26346250 medRxiv
Show abstract

IntroductionThis 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 Alzheimers disease (AD). Methods45 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. ResultsBoth 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. DiscussionPersonalized aiTBS targeting the DMN or FPN produced clinically meaningful cognitive benefits in mild AD and was safe.

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