{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:30:17Z","timestamp":1793313017444,"version":"4.5.0"},"reference-count":32,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Focused ultrasound (FUS)\u2013mediated blood-brain barrier (BBB) opening is safe and potentially beneficial in patients with Alzheimer\u2019s disease (AD) for the removal of amyloid-beta (A\u03b2) 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      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.\n                      <jats:sup>18<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      All 6 participants completed the study without any acute treatment-related adverse events. An extensive area of BBB opening (mean 43.1 cm\n                      <jats:sup>3<\/jats:sup>\n                      ), more than twice as large as the opening volume (mean 20 cm\n                      <jats:sup>3<\/jats:sup>\n                      ) in the authors\u2019 previous study, was confirmed by contrast-enhanced MRI. FBB-PET scans demonstrated a 14.9-Centiloid average decrease in A\u03b2 plaques in 4 of the 6 participants (67%), but the A\u03b2 plaques increased in 2 participants after BBB opening, compared with baseline. No significant changes were observed in the Korean version of the Mini\u2013Mental State Examination in either group. Caregiver-Administered Neuropsychiatric Inventory scores improved in 5 of 6 participants (83%), indicating an improvement in neuropsychiatric symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2024.8.jns24989","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T20:30:36Z","timestamp":1736541036000},"page":"1263-1270","source":"Crossref","is-referenced-by-count":23,"title":["Repetitive and extensive focused ultrasound\u2013mediated bilateral frontal blood-brain barrier opening for Alzheimer\u2019s disease"],"prefix":"10.3171","volume":"142","author":[{"given":"Byoung Seok","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Neurology, Yonsei University College of Medicine, Seoul;"},{"name":"Yonsei Metabolism-Dementia Research Institute, Seoul; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Won","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yonsei University College of Medicine, Seoul;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Yonsei Metabolism-Dementia Research Institute, Seoul; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Woo","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Korea University Anam Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"3","key":"b1","series-title":"Alzheimers Dement","first-page":"263","article-title":"The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"McKhann GM","year":"2011","unstructured":"McKhann GM, Knopman DS, Chertkow H,  The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. 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