Repeated neuromodulation with low-intensity focused ultrasound in patients with Alzheimer's disease
Hyeonseok Jeong, Doyu Kim, Seunghee Na, Byungseok Kim, Jin Kyoung Oh, Eun Kyoung Choi, Sujung Yoon, Marom Bikson, Yong-An Chung, In-Uk Song
Journal of Alzheimer’s Disease 2025, 105, 955-965 · 10.1177/13872877251333614
Abstract
BackgroundLow-intensity focused ultrasound (LIFU), a non-invasive targeted brain stimulation technology, has shown promise for therapeutic applications in Alzheimer's disease (AD) patients. Despite its potential, the implications of repeated LIFU neuromodulation in AD patients remain to be investigated.ObjectiveThis pilot study evaluated the safety and potential to improve cognition and functional connectivity following repeated LIFU treatment in AD patients.MethodsTen early-stage AD patients underwent six sessions of neuronavigation-guided LIFU targeting the left dorsolateral prefrontal cortex (DLPFC) within 2-3 weeks, alongside ongoing standard pharmacotherapy. Neuropsychological assessments and resting-state functional magnetic resonance imaging were performed at baseline and eight weeks post-treatment.ResultsMemory performance (p = 0.02) and functional connectivity between the left DLPFC and both the left perirhinal cortex and left dorsomedial prefrontal cortex (corrected p < 0.05) significantly improved from baseline. Additionally, enhancements in memory performance were positively correlated with increases in functional connectivity of the left DLPFC with the left perirhinal cortex (Kendall's tau = 0.56, p = 0.03). No adverse events were reported during the LIFU treatments or at the subsequent follow-up.ConclusionsLIFU may have the therapeutic potential to enhance both brain network connectivity and memory functions in AD patients. Our results provide a basis for further research, including randomized sham-controlled trials and optimization of stimulation protocols, on LIFU as a supplementary or alternative treatment option for AD.Trial registrationClinical Research Information Service, KCT0008169, Registered on 10 February 2023.
Abstract via europepmc.
Exposures
Exposure 1: Repeated neuronavigation-guided LIFU to the left dorsolateral prefrontal cortex
Target: dorsolateral prefrontal cortex — “left dorsolateral prefrontal cortex (DLPFC; Brodmann area [BA] 46)”
Device: Neurosona · Neurosona Co., Ltd · NS-US200 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| 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) | 3 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 1.5 | ✓✓✓⚑ |
For each session, the ultrasound stimulation was delivered for 20 min with the following parameters based on previous LIFU studies in healthy volunteers and patients with major depressive disorder. The ultrasound focus was formed 30 mm from the exit plane of the transducer, and the focal size was 4 mm in diameter and 18 mm in length at 90% maximum intensity. Patients were scheduled to receive a total of six treatments over a two-week period (extended to three weeks if needed).
Flags from extraction
randomised— Single-arm, uncontrolled pilot design with no sham/comparison group; not explicitly described as randomised or non-randomised.blinding— No sham/control arm is used, so blinding could not be implemented; not explicitly stated by the authors.exposures[0].unspecified_domain.isppa_w_cm2— The parameter list attaches the label 'in situ' only to the mechanical index; it is unclear whether the adjacent ISPPA/ISPTA values are also in-situ (brain-target) estimates or free-field settings, so they are recorded as unspecified domain.exposures[0].unspecified_domain.ispta_w_cm2— Same ambiguity as ISPPA: domain not explicitly stated for this intensity value.