{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T06:57:36Z","timestamp":1794466656297,"version":"4.9.1"},"reference-count":51,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Repetitive transcranial magnetic stimulation (rTMS) has emerged as a safe and promising intervention for Alzheimer disease (AD).<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the effect of a 4-week personalized hippocampal network\u2013targeted rTMS on cognitive and functional performance, as well as functional connectivity in AD.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This randomized clinical trial, which was sham-controlled and masked to participants and evaluators, was conducted between May 2020 and April 2022 at a single Korean memory clinic. Eligible participants were between ages 55 and 90 years and had confirmed early AD with evidence of an amyloid biomarker. Participants who met the inclusion criteria were randomly assigned to receive hippocampal network\u2013targeted rTMS or sham stimulation. Participants received 4-week rTMS treatment, with assessment conducted at weeks 4 and 8. Data were analyzed between April 2022 and January 2024.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Each patient received 20 sessions of personalized rTMS targeting the left parietal area, functionally connected to the hippocampus, based on fMRI connectivity analysis over 4 weeks. The sham group underwent the same procedure, excluding actual magnetic stimulation. A personalized 3-dimensional printed frame to fix the TMS coil to the optimal target site was produced.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was the change in the AD Assessment Scale-Cognitive Subscale test (ADAS-Cog) after 8 weeks from baseline. Secondary outcomes included changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Seoul-Instrumental Activity Daily Living (S-IADL) scales, as well as resting-state fMRI connectivity between the hippocampus and cortical areas.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 30 participants (18 in the rTMS group; 12 in the sham group) who completed the 8-week trial, the mean (SD) age was 69.8 (9.1) years; 18 (60%) were female. As the primary outcome, the change in ADAS-Cog at the eighth week was significantly different between the rTMS and sham groups (coefficient [SE], \u22125.2 [1.6];\n P<\/jats:italic>\n \u2009=\u2009.002). The change in CDR-SOB (\u22124.5 [1.4];\n P<\/jats:italic>\n \u2009=\u2009.007) and S-IADL (1.7 [0.7];\n P<\/jats:italic>\n \u2009=\u2009.004) were significantly different between the groups favoring rTMS groups. The fMRI connectivity analysis revealed that rTMS increased the functional connectivity between the hippocampus and precuneus, with its changes associated with improvements in ADAS-Cog (\n r<\/jats:italic>\n \u2009=\u2009\u22120.57;\n P<\/jats:italic>\n \u2009=\u2009.005).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This randomized clinical trial demonstrated the positive effects of rTMS on cognitive and functional performance, and the plastic changes in the hippocampal-cortical network. Our results support the consideration of rTMS as a potential treatment for AD.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04260724<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.9220","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T11:01:34Z","timestamp":1714993294000},"page":"e249220","source":"Crossref","is-referenced-by-count":81,"title":["Effectiveness of Personalized Hippocampal Network\u2013Targeted Stimulation in Alzheimer Disease"],"prefix":"10.1001","volume":"7","author":[{"given":"Young Hee","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Neurology, Myongji Hospital, Hanyang University, Goyang, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyemin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National 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Health Science & Technology, Sungkyunkwan University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Won","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea"},{"name":"Samsung Alzheimer Research Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea"},{"name":"Department of Health Science and Technology, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, Korea"},{"name":"Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guk Bae","family":"Kim","sequence":"additional","affiliation":[{"name":"Anymedi Inc, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Min","family":"Shon","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, Korea"},{"name":"Smart Healthcare Research Institute, Samsung Medical Center, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungshin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Artificial Intelligence, Hanyang University, Seoul, Korea"},{"name":"Department of Data Science, Hanyang University, Seoul, Korea"},{"name":"Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Korea"},{"name":"Department of Healthcare Digital Engineering, Hanyang University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duk L.","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Neurology, 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