Effects of Low-Intensity Ultrasound on Amyloid-β Clearance in Early-Stage Alzheimer′s Disease: A Potential Role of Glymphatic Activity

IF 2.7 3区医学 Q2 CLINICAL NEUROLOGY

Acta Neurologica Scandinavica Pub Date : 2026-02-18 DOI:10.1155/ane/1538313

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

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引用次数: 0

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Trial Registration

Clinicaltrial.gov identifier: NCT05633095

Abstract Image

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低强度超声对早期阿尔茨海默病中淀粉样蛋白-β清除的影响：淋巴活性的潜在作用

目的阿尔茨海默病（AD）涉及代谢废物（包括淀粉样蛋白-β）的清除受损，可能与淋巴功能障碍有关。低强度超声（LIUS）可以促进脑内溶质的清除。这项初步研究探讨了LIUS是否会影响早期AD患者的淀粉样蛋白-β沉积和认知能力，以及mri引起的假定的淋巴活性变化是否可能是潜在的机制。这项前瞻性先导研究（2022年9月至2023年2月）招募了10名淀粉样蛋白阳性的参与者，他们接受了4周的LIUS治疗，其中包括5名载脂蛋白E4 （APOE4）携带者和5名非携带者。LIUS治疗包括4周以上的疗程。采用磁共振成像（MRI）和淀粉样蛋白PET扫描定量分析淋巴活性、血脑屏障（BBB）完整性、微出血发生率和淀粉样蛋白沉积变化。使用神经心理学测试评估认知变化。结果所有受试者均完成治疗，无明显不良事件发生。神经心理测试显示认知功能有所改善。淀粉样蛋白-β沉积主要在APOE4携带者中减少。此外，lius后，大脑皮层显示假定的淋巴活性增加，尽管多次比较校正后没有保持统计学意义。在血脑屏障完整性、微出血发生率或脑容量方面未观察到显著变化。结论LIUS是一种安全的治疗方法，可改善早期AD患者的认知功能，减少淀粉样蛋白沉积。这些作用可能反映了LIUS的一些生物学作用，包括增强淋巴细胞的可能性。有必要对更大的队列和适当的对照组进行进一步的研究，以证实这些发现并得出更明确的结论。临床试验注册。gov识别码：NCT05633095

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来源期刊

Acta Neurologica Scandinavica 医学-临床神经学

CiteScore

6.70

自引率

2.90%

发文量

161

审稿时长

4-8 weeks

期刊介绍： Acta Neurologica Scandinavica aims to publish manuscripts of a high scientific quality representing original clinical, diagnostic or experimental work in neuroscience. The journal''s scope is to act as an international forum for the dissemination of information advancing the science or practice of this subject area. Papers in English will be welcomed, especially those which bring new knowledge and observations from the application of therapies or techniques in the combating of a broad spectrum of neurological disease and neurodegenerative disorders. Relevant articles on the basic neurosciences will be published where they extend present understanding of such disorders. Priority will be given to review of topical subjects. Papers requiring rapid publication because of their significance and timeliness will be included as ''Clinical commentaries'' not exceeding two printed pages, as will ''Clinical commentaries'' of sufficient general interest. Debate within the speciality is encouraged in the form of ''Letters to the editor''. All submitted manuscripts falling within the overall scope of the journal will be assessed by suitably qualified referees.