Effects of Low‐Intensity Ultrasound on Amyloid‐ β Clearance in Early‐Stage Alzheimer′s Disease: A Potential Role of Glymphatic Activity
Sang Won Jo, Bo-yong Park, Roh-Eul Yoo, Seung Hong Choi, Sooyeon Ji, Tae Young Park, Hyungmin Kim, Seongbeom Park, Min Seung Kim, Suk Yun Kang, Soo-Jin Cho, Won-Jin Moon, SangYun Kim, Jaeho Kim
Acta Neurologica Scandinavica 2026 · 10.1155/ane/1538313
Abstract
Alzheimer′s disease (AD) involves impaired clearance of metabolic waste, including amyloid‐ β , potentially related to glymphatic dysfunction. Low‐intensity ultrasound (LIUS) may facilitate solute clearance in the brain. This pilot study examined whether LIUS affects amyloid‐ β deposition and cognitive performance in early‐stage AD, and whether MRI‐derived changes in putative glymphatic activity could represent a possible underlying mechanism. This prospective pilot study (September 2022–February 2023) enrolled 10 amyloid‐positive participants who underwent 4 weeks of LIUS treatment, including five apolipoprotein E4 (APOE4) carriers and five noncarriers. LIUS treatment involved sessions over 4 weeks. Magnetic resonance imaging (MRI) and amyloid PET scans were used to quantitatively analyze glymphatic activity, blood–brain barrier (BBB) integrity, microbleed occurrence, and amyloid deposition changes. Cognitive changes were assessed using neuropsychological tests. All participants completed treatment without any significant adverse events. Neuropsychological testing demonstrated cognitive function improvements. Amyloid‐ β deposition decreased mainly in APOE4 carriers following LIUS. In addition, post‐LIUS, the cerebral cortex showed increased putative glymphatic activity, although statistical significance was not maintained after multiple‐comparison correction. No significant changes were observed in BBB integrity, microbleed occurrence, or brain volume. LIUS was safe and demonstrated both cognitive improvement and reduced amyloid deposition in early‐stage AD. These effects may reflect several biological actions of LIUS, including the possibility of glymphatic enhancement. Further studies with larger cohorts and appropriate control groups are warranted to confirm these findings and draw more definitive conclusions. Clinicaltrial.gov identifier: NCT05633095
Abstract via crossref.
Exposures
Exposure 1: LIUS, four unfocused transducers
Target: whole brain or unfocused — “posterior fontanelle and lateral area of the head (unfocused transducers)”
Device: other named manufacturer · Deepson Bio · Neuclare ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 100 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 1,800 | ✓✓✓ |
| Free-field pressure (kPa) | 390 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | ⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 280 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 2.6 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.26 | ✓✓✓ |
Pulse duration 100 ms at 1 Hz PRF; 30 min of sonication per session, three sessions per week for 4 weeks, four unfocused transducers positioned in pairs on the front and sides of the head.
Flags from extraction
n_sessions_per_subject— Twelve is three sessions per week for 4 weeks, my arithmetic; the paper does not state the total.exposures[0].in_situ.isppa_w_cm2— Intensity units garbled in the extraction (W cm-2 -1); values 2.6 and 0.26 read in order Isppa, Ispta, MI.exposures[0].free_field.isppa_w_cm2— No free-field intensity given.exposures[0].target.terms— Unfocused multi-transducer whole-head exposure; no focal target.sham_type— Single-arm pilot, no control group.