{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:23:48Z","timestamp":1787829828462,"version":"build-2784847793"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deepson Bio, Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background: Low-intensity ultrasound (LIUS) has been proposed as a non-invasive approach to modulate cerebrospinal fluid movement, glymphatic\u2013lymphatic clearance, and amyloid-beta (A\u03b2) handling in Alzheimer\u2019s disease (AD). However, clinical comparisons in amyloid biomarker-confirmed patients receiving standard pharmacotherapy remain limited, and the short-term cognitive domains most likely to change after LIUS remain uncertain. Objective: The objective of this study was to compare 4-week changes in cognitive function, executive function, quality of life, and neuropsychiatric symptoms between amyloid PET-positive patients receiving add-on LIUS with donepezil-based standard treatment and those receiving donepezil-based standard treatment alone. Methods: This retrospective exploratory comparative cohort study included amyloid PET-positive patients with mild cognitive impairment or early AD who received donepezil-based standard treatment. The treatment cohort received 4 weeks of add-on LIUS at Dongtan or Bundang centers, whereas the comparator cohort received donepezil-based standard treatment alone at Soonchunhyang. Outcomes were changes from baseline to 4 weeks in Trail Making Test A (TMT-A), Trail Making Test B (TMT-B), Mini-Mental State Examination, Second Edition (MMSE-II), Quality of Life in Alzheimer\u2019s Disease (QoL-AD), and Neuropsychiatric Inventory (NPI). Group differences were examined using unadjusted change-score comparisons and stabilized inverse probability of treatment weighting (IPTW). Results: The full analysis set included 51 amyloid PET-positive participants receiving donepezil-based standard treatment: 20 who additionally received LIUS and 31 who received standard treatment alone. Compared with controls, the add-on LIUS group showed greater improvement in TMT-A completion time in unadjusted analysis (\u221220.0 \u00b1 31.3 s vs. \u22120.1 \u00b1 5.6 s; p = 0.011), and this association remained significant after IPTW adjustment. TMT-B showed a favorable but less robust pattern, with borderline findings in the primary Fail-excluded analyses and a significant result in the Fail = 300 sensitivity analysis. MMSE-II change did not differ between groups. NPI improved more in the add-on LIUS group in unadjusted analysis, although this finding was exploratory. Conclusions: In amyloid PET-positive patients receiving donepezil-based standard treatment, 4 weeks of add-on LIUS was associated with short-term improvement in TMT-A performance compared with standard treatment alone, while MMSE-II remained unchanged. The findings suggest a preliminary signal for processing-speed or visual-search improvement and support prospective randomized sham-controlled studies with harmonized cognitive testing and biomarker endpoints.<\/jats:p>","DOI":"10.3390\/brainsci16090913","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:21Z","timestamp":1787828301000},"page":"913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-Term Cognitive and Behavioral Changes After Low-Intensity Transcranial Ultrasound Stimulation in Early Alzheimer\u2019s Disease: An IPTW-Adjusted Retrospective Exploratory Comparative Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-2599","authenticated-orcid":false,"given":"YoungSoon","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan 31151, Chungcheongnam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hallym University College of Medicine, Dongtan Sacred Heart Hospital, Hwaseong 18450, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngsuep","family":"Kang","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital Healthcare Innovation Park, Seongnam 13605, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5674-8768","authenticated-orcid":false,"given":"Seungho","family":"Choi","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital Healthcare Innovation Park, Seongnam 13605, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8401-3815","authenticated-orcid":false,"given":"Jeonghyeon","family":"Seo","sequence":"additional","affiliation":[{"name":"Seoul National University Bundang Hospital Healthcare Innovation Park, Seongnam 13605, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-5704","authenticated-orcid":false,"given":"SangYun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Bundang Hospital, Seongnam 13620, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. 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