{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:57:19Z","timestamp":1786978639997,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":68,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Brain network dysfunction, particularly within the default mode network (DMN), is an increasingly apparent contributor to the clinical progression of Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) can target key DMN hubs, maintain signaling function, and delay or improve clinical outcomes in AD. Here, we present the rationale and design of a study using off\u2010the\u2010shelf equipment and the latest clinical evidence to expand on prior rTMS work and reduce participant burden in the process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We will conduct a two\u2010stage trial of large\u2010coil rTMS targeting the precuneus (a key hub in the DMN affected by AD) in 54 participants with mild to moderate Alzheimer's Clinical Syndrome focused primarily on determining tolerability and feasibility and secondarily focused on determining short\u2010term efficacy for memory. The first stage will involve 5 to 10 participants receiving open\u2010label active treatment to refine the protocol. The following second stage will consist of a 1:1 randomized, double\u2010blind, sham\u2010controlled clinical trial to study feasibility and tolerability while exploring target engagement and short\u2010term efficacy for memory. Participants will undergo 16 total rTMS brain stimulation sessions over the course of 5 weeks. A full course of open\u2010label active treatment will be offered as an extension to the sham group after unblinding. Outcomes will focus on completion rates and adverse events to demonstrate feasibility and tolerability. Further exploratory outcomes will include neuropsychological assessments, electroencephalography, neuroimaging, and blood biomarkers to demonstrate the feasibility of collection and explore preliminary changes in these measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We anticipate this treatment is feasible and tolerable and may show evidence of target engagement and clinical improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Should we achieve expected positive outcomes in feasibility and tolerability, this will justify future work focusing on clear demonstrations of clinical efficacy and biomarker engagement, as well as enhancement of generalizability and scalability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Induction\u2010to\u2010maintenance repetitive transcranial magnetic stimulation (rTMS) of the precuneus is a promising treatment for Alzheimer's disease (AD), though recent methods require intensive personalization.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We propose here a trial design of precuneus rTMS in mild\u2010to\u2010early\u2010moderate AD dementia using exclusively off\u2010the\u2010shelf equipment and protocol modifications to reduce participant burden.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our two novel modifications from prior work are (1) using a larger rTMS coil, and (2) consolidating the induction phase of treatment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This trial focuses primarily on tolerability and feasibility while exploring clinical measures of efficacy and biomarkers of target engagement.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our trial is registered at ClinicalTrials.gov NCT06597942.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70043","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:06:23Z","timestamp":1741741583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Broad repetitive transcranial magnetic stimulation (rTMS) of the precuneus in Alzheimer's disease: A rationale and study design"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-6721","authenticated-orcid":false,"given":"Michael K.","family":"Leuchter","sequence":"first","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanadi A.","family":"Oughli","sequence":"additional","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Durbin","sequence":"additional","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Medicine Statistics Core David Geffen School of Medicine at UCLA  Los Angeles California USA"},{"name":"Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Elashoff","sequence":"additional","affiliation":[{"name":"Department of Medicine Statistics Core David Geffen School of Medicine at UCLA  Los Angeles California USA"},{"name":"Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Chang","sequence":"additional","affiliation":[{"name":"Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Corlier","sequence":"additional","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doan","family":"Ngo","sequence":"additional","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Matthews","sequence":"additional","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darice","family":"Wong","sequence":"additional","affiliation":[{"name":"UCLA Clinical Neurogenomics Research Center, David Geffen School of Medicine University of California  Los Angeles California USA"},{"name":"Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent L.","family":"Fogel","sequence":"additional","affiliation":[{"name":"UCLA Clinical Neurogenomics Research Center, David Geffen School of Medicine University of California  Los Angeles California USA"},{"name":"Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gal","family":"Bitan","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles California USA"},{"name":"Brain Research Institute University of California, Los Angeles  Los Angeles California USA"},{"name":"Molecular Biology Institute University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Leuchter","sequence":"additional","affiliation":[{"name":"TMS Clinical and Research Program, Neuromodulation Division Semel Institute for Neuroscience and Human Behavior at UCLA  Los Angeles California USA"},{"name":"Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at UCLA  Los Angeles California USA"},{"name":"Brain Research Institute University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Vossel","sequence":"additional","affiliation":[{"name":"Mary S. 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