Home-administered unfocused transcranial ultrasound in subjective cognitive decline and dementia: an open-label, uncontrolled feasibility pilot study
Helané Wahbeh, Sterling Cooley, Steven Russell Chamberlin, Thomas Brophy, Stuart Hameroff
Frontiers in Aging Neuroscience 2026 · 10.3389/fnagi.2026.1937897
Abstract
Background Memory and cognitive impairments remain disabling, with few effective treatments. Low-intensity transcranial ultrasound (TUS) is a non-invasive neuromodulation approach with a favorable safety profile and preliminary evidence of cognitive benefit, with one hypothesized but unproven mechanism involving microtubule resonance and reassembly. Objectives This open-label pilot study evaluated the safety and preliminary efficacy of the US Pro2000 unfocused ultrasound device in adults with memory or cognitive difficulties, a sample spanning subjective cognitive decline among self-administering participants to diagnosed dementia among caregiver-rated recipients, and described self-reported symptom trajectories. Methods In a within-participant design, adults with self-reported cognitive impairment, or their caregivers, applied the device at the right temporal window for 5 min three times daily (target 15 min/day), in cycles of 3 weeks on and 1 week off. Outcomes (GAD-7, CESD-5, Inoue battery, and caregiver-rated MDS 3.0) and adverse events were collected online. Mixed-effects models with age and device-use covariates assessed change over time, with False Discovery Rate correction within aim. Results Twenty-seven participants enrolled and 26 initiated treatment. Across 2,174 daily assessments, no serious or unanticipated adverse events occurred; only headache (15.4%) and transient jaw clenching (3.8%) were possibly related, and none caused discontinuation. Among self-administered participants, depression (CESD-5) declined significantly ( p _FDR = 0.016) and five of eight monthly self-report symptoms improved, including memory, word-finding, and problem-solving (all p _FDR ≤ 0.040); anxiety trended downward, and the objective cognitive battery, near ceiling at baseline, did not change. Caregiver-rated outcomes were stable. Device use showed no dose response, and sensitivity analyses were consistent. Conclusion Home-based self-administered low-intensity TUS was well tolerated, with only mild transient events, although adverse-event ascertainment relied on unblinded self-report and relatedness judgments were made by unblinded investigators. Efficacy signals were confined to self-report, while objective cognition and caregiver ratings were unchanged. The uncontrolled design, small subgroups, and reliance on self-report preclude causal inference. These findings support the safety and feasibility of TUS and justify an adequately powered, double-blind, sham-controlled trial.
Abstract via europepmc.
Exposures
Exposure 1: Unfocused 1 MHz TUS at right temporal window (LOW setting)
Target: temporal lobe, frontal lobe — “right temporal window, targeting frontotemporal brain regions”
Device: not reported · US Pro2000 (Model DU3035) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 8 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.4 | ✓✓✓ |
Three 5-min sessions per day (alternatively two 7.5-min), in cycles of 3 consecutive weeks of daily use followed by a 1-week break, repeated for the duration of participation. Self-administered at home.
Flags from extraction
exposures[0].unspecified_domain.isppa_w_cm2— Spatial-peak values at the transducer face derived from manufacturer labeling (spatial-average 1.6 W/cm2 SAPA, 0.08 W/cm2 SATA times nonuniformity ratio 5); not independently measured; domain not stated as water or tissueexposures[0].device— Device is US Pro2000 (Model DU3035), a physiotherapy unit used off-label; manufacturer not namedexposures[0].timing.sonication_duration_s— Three 5-min sessions per day (or two 7.5-min), 3 weeks on / 1 week off; 5 min taken as one sessionn_subjects— 27 enrolled, 26 initiated treatment; 26 recordedexposures[0].target— Unfocused beam applied at right temporal window; target not a defined focal site