{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T23:03:12Z","timestamp":1794092592315,"version":"4.8.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006312","name":"Brightfocus Foundation","doi-asserted-by":"crossref","award":["A2019523S"],"award-info":[{"award-number":["A2019523S"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Repetitive transcranial magnetic stimulation (rTMS) is emerging as a non-invasive therapeutic strategy in the battle against Alzheimer\u2019s disease. Alzheimer\u2019s disease patients primarily show alterations of the default mode network for which the precuneus is a key node. Here, we hypothesized that targeting the precuneus with TMS represents a promising strategy to slow down cognitive and functional decline in Alzheimer\u2019s disease patients.<\/jats:p>\n                  <jats:p>We performed a randomized, double-blind, sham-controlled, phase 2, 24-week trial to determine the safety and efficacy of precuneus stimulation in patients with mild-to-moderate Alzheimer\u2019s disease. Fifty Alzheimer\u2019s disease patients were randomly assigned in a 1:1 ratio to either receive precuneus or sham rTMS (mean age 73.7 years; 52% female). The trial included a 24-week treatment, with a 2-week intensive course in which rTMS (or sham) was applied daily five times per week, followed by a 22-week maintenance phase in which stimulation was applied once weekly. The Clinical Dementia Rating Scale\u2013Sum of Boxes was selected as the primary outcome measure, in which post-treatment scores were compared to baseline. Secondary outcomes included score changes in the Alzheimer\u2019s Disease Assessment Scale\u2013Cognitive Subscale, Mini-Mental State Examination and Alzheimer\u2019s Disease Cooperative Study\u2013Activities of Daily Living scale. Moreover, single-pulse TMS in combination with EEG was used to assess neurophysiological changes in precuneus cortical excitability and oscillatory activity.<\/jats:p>\n                  <jats:p>Our findings show that patients that received precuneus repetitive magnetic stimulation presented a stable performance of the Clinical Dementia Rating Scale\u2013Sum of Boxes score, whereas patients treated with sham showed a worsening of their score. Compared with the sham stimulation, patients in the precuneus stimulation group also showed also significantly better performances for the secondary outcome measures, including the Alzheimer\u2019s Disease Assessment Scale\u2013Cognitive Subscale, Mini-Mental State Examination and Alzheimer\u2019s Disease Cooperative Study\u2013Activities of Daily Living scale. Neurophysiological results showed that precuneus cortical excitability remained unchanged after 24 weeks in the precuneus stimulation group, whereas it was significantly reduced in the sham group. Finally, we found an enhancement of local gamma oscillations in the group treated with precuneus stimulation but not in patients treated with sham.<\/jats:p>\n                  <jats:p>We conclude that 24 weeks of precuneus rTMS may slow down cognitive and functional decline in Alzheimer\u2019s disease. Repetitive TMS targeting the default mode network could represent a novel therapeutic approach in Alzheimer\u2019s disease patients.<\/jats:p>","DOI":"10.1093\/brain\/awac285","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T14:01:26Z","timestamp":1661349686000},"page":"3776-3786","source":"Crossref","is-referenced-by-count":270,"title":["Precuneus magnetic stimulation for Alzheimer\u2019s disease: a randomized, sham-controlled trial"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6155-9439","authenticated-orcid":false,"given":"Giacomo","family":"Koch","sequence":"first","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"},{"name":"Department of Neuroscience and Rehabilitation, University of Ferrara, and Center for Translational Neurophysiology of Speech and Communication (CTNSC), Italian Institute of Technology (IIT) , 44121, Ferrara , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias Paolo","family":"Casula","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Bonn\u00ec","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Borghi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Assogna","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"},{"name":"Memory Clinic, Department of Systems Medicine, University of Tor Vergata , 00133, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Minei","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concetta","family":"Pellicciari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Motta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS , 00179, Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"D\u2019Acunto","sequence":"additional","affiliation":[{"name":"Department of Clinical and 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