The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Repetitive and extensive focused ultrasound–mediated bilateral frontal blood-brain barrier opening for Alzheimer’s disease
Open accessAbstract
OBJECTIVE: Focused ultrasound (FUS)–mediated blood-brain barrier (BBB) opening is safe and potentially beneficial in patients with Alzheimer’s disease (AD) for the removal of amyloid-beta (Aβ) plaques. However, the optimal BBB opening intervals and number of treatment sessions for clinical improvement remain undefined. Therefore, the aim of this study was to evaluate the safety and benefits of repeated and more extensive BBB opening alone. METHODS: In this open-label prospective study, 6 patients with AD were enrolled from June 2022 to July 2023. FUS-mediated BBB opening was performed three times at 2-month intervals targeting the bilateral frontal lobes. 18 F-florbetaben positron emission tomography (FBB-PET) was performed before the first procedure and after the third procedure. Patients were administered neuropsychological and neuropsychiatric evaluations. RESULTS: All 6 participants completed the study without any acute treatment-related adverse events. An extensive area of BBB opening (mean 43.1 cm 3 ), more than twice as large as the opening volume (mean 20 cm 3 ) in the authors’ previous study, was confirmed by contrast-enhanced MRI. FBB-PET scans demonstrated a 14.9-Centiloid average decrease in Aβ plaques in 4 of the 6 participants (67%), but the Aβ plaques increased in 2 participants after BBB opening, compared with baseline. No significant changes were observed in the Korean version of the Mini–Mental State Examination in either group. Caregiver-Administered Neuropsychiatric Inventory scores improved in 5 of 6 participants (83%), indicating an improvement in neuropsychiatric symptoms. CONCLUSIONS: This study confirmed the safety and efficacy of more frequent and extensive bilateral frontal BBB opening over multiple sessions in patients with AD. Furthermore, this is the first clinical trial to demonstrate improvement in neuropsychiatric symptoms through BBB opening alone, without concurrent administration of antibody medications.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Donanemab in Early Alzheimer’s Disease
Mintun, M. A., Lo, A. C., Duggan Evans, C., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., Shcherbinin, S., Sparks, J., Sims, J. R., Brys, M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2100708 · Cited by 1,728
Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound.
Rezai, A. R., Ranjan, M., D’Haese, P.-F., Haut, M. W., Carpenter, J., Najib, U., Mehta, R. I., Chazen, J. L., Zibly, Z., Yates, J. R., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002571117 · Cited by 365
Flagged first, then by citations
Research works printed but not linked: 26
- McKhann GM, Knopman DS, Chertkow H, The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–269.
- Sims JR, Zimmer JA, Evans CD, Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512–527.
- Zeng BS, Tseng PT, Liang CS. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(17):1630.
- Chen KT, Wei KC, Liu HL. Theranostic strategy of focused ultrasound induced blood-brain barrier opening for CNS disease treatment. Front Pharmacol. 2019;10:86.
- Lipsman N, Meng Y, Bethune AJ, Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat Commun. 2018;9(1):2336.
- Park SH, Baik K, Jeon S, Chang WS, Ye BS, Chang JW. Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study. Transl Neurodegener. 2021;10(1):44.
- Kang SJ, Choi SH, Lee BH, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI). J Geriatr Psychiatry Neurol. 2004;17(1):32–35.
- Klunk WE, Koeppe RA, Price JC, The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11(1):1-15.e1–4.
- Ryu HJ, Yang DW. The Seoul Neuropsychological Screening Battery (SNSB) for comprehensive neuropsychological assessment. Dement Neurocognitive Disord. 2023;22(1):1–15.
- Rezai AR, D’Haese PF, Finomore V, Ultrasound blood-brain barrier opening and aducanumab in Alzheimer’s disease. N Engl J Med. 2024;390(1):55–62.
- VandeVrede L, La Joie R, Horiki S, Co-pathology may impact outcomes of amyloid-targeting treatments: clinicopathological results from two patients treated with aducanumab. Acta Neuropathol. 2023;146(5):777–781.
- van Dyck CH, Swanson CJ, Aisen P, Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21.
- McKhann GM, Knopman DS, Chertkow H, The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–269.
- Sims JR, Zimmer JA, Evans CD, Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512–527.
- Zeng BS, Tseng PT, Liang CS. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(17):1630.
- Chen KT, Wei KC, Liu HL. Theranostic strategy of focused ultrasound induced blood-brain barrier opening for CNS disease treatment. Front Pharmacol. 2019;10:86.
- Lipsman N, Meng Y, Bethune AJ, Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat Commun. 2018;9(1):2336.
- Rezai AR, Ranjan M, D’Haese PF, Noninvasive hippocampal blood-brain barrier opening in Alzheimer’s disease with focused ultrasound. Proc Natl Acad Sci U S A. 2020;117(17):9180–9182.
- Park SH, Baik K, Jeon S, Chang WS, Ye BS, Chang JW. Extensive frontal focused ultrasound mediated blood-brain barrier opening for the treatment of Alzheimer’s disease: a proof-of-concept study. Transl Neurodegener. 2021;10(1):44.
- Kang SJ, Choi SH, Lee BH, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI). J Geriatr Psychiatry Neurol. 2004;17(1):32–35.
- Klunk WE, Koeppe RA, Price JC, The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement. 2015;11(1):1-15.e1–4.
- Ryu HJ, Yang DW. The Seoul Neuropsychological Screening Battery (SNSB) for comprehensive neuropsychological assessment. Dement Neurocognitive Disord. 2023;22(1):1–15.
- Rezai AR, D’Haese PF, Finomore V, Ultrasound blood-brain barrier opening and aducanumab in Alzheimer’s disease. N Engl J Med. 2024;390(1):55–62.
- VandeVrede L, La Joie R, Horiki S, Co-pathology may impact outcomes of amyloid-targeting treatments: clinicopathological results from two patients treated with aducanumab. Acta Neuropathol. 2023;146(5):777–781.
- van Dyck CH, Swanson CJ, Aisen P, Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21.
- Mintun MA, Lo AC, Duggan Evans C, Donanemab in early Alzheimer’s disease. N Engl J Med. 2021;384(18):1691–1704.
Metadata
- Authors
- Ye, B. S., Chang, K. W., Kang, S., Jeon, S., & Chang, J. W.
- Affiliations
- Yonsei University (KR)
- Samsung Medical Center (KR)
- Department of Neurology, Yonsei University College of Medicine, Seoul;
- Korea University Anam Hospital (KR)
- Venue
- Journal of Neurosurgery
- Published
- 2025-05-01
- Volume
- 142
- Issue
- 5
- Pages
- 1263-1270
- ISSN
- 0022-3085 (ISSN-L)
- 1933-0693
- OpenAlex
- W4406241089
- Cited by
- 22
- References
- 2
- Citations by year
- 2026: 14 · 2025: 8
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of neurosurgery (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Focused Ultrasound Foundation
- Korea Health Industry Development Institute (HR22C141101)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Alzheimer's disease, focused ultrasound, blood-brain barrier opening, amyloid plaques, amyloid PET, 18F-florbetaben, neuropsychiatric symptoms, treatment safety
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Blood-Brain Barrier, Female, Frontal Lobe, Humans, Male, Middle Aged, Prospective Studies, Ultrasonic Therapy, Treatment Outcome, Positron-Emission Tomography
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
