Safety and efficacy of transcranial ultrasound stimulation for the treatment of Alzheimer’s disease: A randomized, double-blind, placebo-controlled trial

Abstract

Transcranial ultrasound stimulation (TUS) has emerged as a potential neuromodulatory intervention for Alzheimer’s disease (AD). This pilot randomized, double-blind, placebo-controlled trial evaluated TUS’s safety and preliminary efficacy in patients with mild AD. Patients aged 50–90 years were enrolled and randomly assigned at a 2:1 ratio to receive TUS treatment for 30 sessions (15 min/day, 5 days/week for 6 weeks) or a placebo procedure. Safety was monitored through magnetic resonance imaging, adverse event reporting, and laboratory assessments. Efficacy was assessed with the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) and the Mini-Mental State Examination (MMSE). Nine of 30 patients screened were enrolled (six TUS, three placebo). All patients completed the study, and no serious clinical or radiographic adverse events related to TUS were observed. At 52 weeks, the change in ADAS-cog score from baseline remained relatively stable in the TUS group compared to worsening in the placebo group (0.5 ± 4.7 vs. 5.0 ± 4.0, p = 0.237), particularly in the memory domain. The change in MMSE score from baseline showed a significant benefit in the TUS group at 24 weeks compared to placebo (2.2 ± 2.2 vs. −3.0 ± 2.6, p < 0.05), and this improvement persisted to 52 weeks. This study demonstrates the safety and feasibility of repeated TUS sessions in AD and suggests potential benefits in preserving cognitive function. Larger, adequately powered trials are required to validate these preliminary findings and further define the therapeutic potential of TUS in AD.