Safety and efficacy of transcranial ultrasound stimulation for the treatment of Alzheimer’s disease: A randomized, double-blind, placebo-controlled trial
Jong-Ling Fuh, Shuu-Jiun Wang, Pei-Ning Wang, Hsiu-Mei Wu, Wei-Shen Su, Hsin-Mei Lin, Feng-Yi Yang
Ultrasonics 2026 · 10.1016/j.ultras.2025.107844
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.
Abstract via europepmc.
Exposures
Exposure 1: Bilateral transtemporal TUS, 30 sessions
Target: temporal lobe — “the temporal lobes through the transtemporal windows”
Device: custom-built · National Yang Ming Chiao Tung University · NeuroSound TUS with two fixed 1 MHz transducers ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 20pulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Ispta, domain unspecified (W/cm²) | 0.5 | ✓✓✓⚑ |
About 15 min per day delivered as three 5-min sessions with 5-min rests, five days a week for six weeks (30 sessions); placebo had the transducer on the scalp with output disabled.
Flags from extraction
n_subjects— 9 patients randomised (6 TUS, 3 placebo); n_subjects is the 6 who received ultrasound. The total of 6 is stated only in the Fig. 4 legend and text (six TUS).exposures[0].timing.pulse_duration_ms— Paper says '2-ms burst lengths'; 20 % duty cycle at 100 Hz gives 2 ms, so burst is read as the pulse (resolved by arithmetic).exposures[0].timing.sonication_duration_s— 15 min/day delivered as three 5-min sessions with 5-min rests; 300 s is the length of one 5-min session (5 min x 60).exposures[0].target— Transducers are described as unfocused / wearable LIPUS over the transtemporal windows; target is stated only as the temporal lobes.exposures[0].unspecified_domain.ispta_w_cm2— Ispta given as 500 mW/cm2 (recorded as 0.5 W/cm2) without stating the domain.provenance— Paper states the cohort was previously reported (volume changes) by Huang et al. 2025; possible reanalysis of an already-reported exposure.