Giacomo Koch, Elias Paolo Casula, Sonia Bonnì, Ilaria Borghi, Martina Assogna, Francesco Di Lorenzo, Romina Esposito, Michele Maiella, Alessia D'Acunto, Matteo Ferraresi, Lucia Mencarelli, Valentina Pezzopane, Caterina Motta, Emiliano Santarnecchi, Marco Bozzali, Alessandro Martorana
{"title":"Effects of 52 weeks of precuneus rTMS in Alzheimer's disease patients: a randomized trial.","authors":"Giacomo Koch, Elias Paolo Casula, Sonia Bonnì, Ilaria Borghi, Martina Assogna, Francesco Di Lorenzo, Romina Esposito, Michele Maiella, Alessia D'Acunto, Matteo Ferraresi, Lucia Mencarelli, Valentina Pezzopane, Caterina Motta, Emiliano Santarnecchi, Marco Bozzali, Alessandro Martorana","doi":"10.1186/s13195-025-01709-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Personalized repetitive transcranial magnetic stimulation (rTMS) of the precuneus (PC) is emerging as a new non-invasive therapeutic approach in treating Alzheimer's disease (AD). Here we sought to investigate the effects of 52 weeks of rTMS applied over the PC on cognitive functions in patients with mild-to-moderate dementia due to AD.</p><p><strong>Methods: </strong>Forty-eight patients with mild-to-moderate dementia due to AD were enrolled for the study. Of those 31 patients were extended to 52 weeks after being included in a 24-week trial (NCT03778151) with the same experimental design. The trial included a 52-week treatment with a 2-week intensive course where rTMS (or sham) was applied over the PC daily (5 times per week, Monday to Friday), followed by a 50-week maintenance phase in which the same stimulation was applied once weekly. Personalization of rTMS treatment was established using neuronavigated TMS in combination with electroencephalography (TMS-EEG). The primary outcome measure was change from baseline to week 52 of the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Secondary outcomes included score changes in the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)<sub>11</sub>, Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) and Neuropsychiatric Inventory (NPI). Changes in cortical activity and connectivity were monitored by TMS-EEG.</p><p><strong>Results: </strong>Among 48 patients randomized (mean age 72.8 years; 56% women), 32 (68%) completed the study. Repetitive TMS of the PC (PC-rTMS) had a significant effect on the primary outcome measure. The estimated mean change in CDR-SB after 52 week was 1.36 for PC-rTMS (95% confidence interval (CI) [0.68, 2.04]) and 2.45 for sham-rTMS group (95%CI [1.85, 3.05]). There were also significant effects for the secondary outcomes ADAS-Cog<sub>11</sub>, ADCS-ADL and NPI scores. Stronger DMN connectivity at baseline was associated with favorable response to rTMS treatment.</p><p><strong>Conclusions: </strong>Fifty-two weeks of PC-rTMS may slow down the impairment of cognitive functions, activities of daily living and behavioral disturbances in patients with mild-to-moderate AD. Further multicenter studies are needed to confirm the clinical potential of DMN personalized rTMS.</p><p><strong>Trial registration: </strong>The study was registered on the clinicaltrial.gov website on 07-07-2022 (NCT05454540).</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"69"},"PeriodicalIF":7.9000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963669/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's Research & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13195-025-01709-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Personalized repetitive transcranial magnetic stimulation (rTMS) of the precuneus (PC) is emerging as a new non-invasive therapeutic approach in treating Alzheimer's disease (AD). Here we sought to investigate the effects of 52 weeks of rTMS applied over the PC on cognitive functions in patients with mild-to-moderate dementia due to AD.
Methods: Forty-eight patients with mild-to-moderate dementia due to AD were enrolled for the study. Of those 31 patients were extended to 52 weeks after being included in a 24-week trial (NCT03778151) with the same experimental design. The trial included a 52-week treatment with a 2-week intensive course where rTMS (or sham) was applied over the PC daily (5 times per week, Monday to Friday), followed by a 50-week maintenance phase in which the same stimulation was applied once weekly. Personalization of rTMS treatment was established using neuronavigated TMS in combination with electroencephalography (TMS-EEG). The primary outcome measure was change from baseline to week 52 of the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Secondary outcomes included score changes in the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)11, Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) and Neuropsychiatric Inventory (NPI). Changes in cortical activity and connectivity were monitored by TMS-EEG.
Results: Among 48 patients randomized (mean age 72.8 years; 56% women), 32 (68%) completed the study. Repetitive TMS of the PC (PC-rTMS) had a significant effect on the primary outcome measure. The estimated mean change in CDR-SB after 52 week was 1.36 for PC-rTMS (95% confidence interval (CI) [0.68, 2.04]) and 2.45 for sham-rTMS group (95%CI [1.85, 3.05]). There were also significant effects for the secondary outcomes ADAS-Cog11, ADCS-ADL and NPI scores. Stronger DMN connectivity at baseline was associated with favorable response to rTMS treatment.
Conclusions: Fifty-two weeks of PC-rTMS may slow down the impairment of cognitive functions, activities of daily living and behavioral disturbances in patients with mild-to-moderate AD. Further multicenter studies are needed to confirm the clinical potential of DMN personalized rTMS.
Trial registration: The study was registered on the clinicaltrial.gov website on 07-07-2022 (NCT05454540).
期刊介绍：
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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