{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T18:21:12Z","timestamp":1776018072962,"version":"3.50.1"},"posted":{"date-parts":[[2025,4,19]]},"group-title":"Neurology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T00:00:00Z","timestamp":1745020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,19]]},"abstract":"<jats:label>1.<\/jats:label>\n                <jats:title>Structured Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disorder for which there is no effective pharmacological treatment. Recent evidence proposes the use of Non-invasive brain stimulation (NIBS) to counteract the typical clinical and neurophysiological degeneration. NIBS protocols require multiple sessions in clinical settings, making long interventions difficult. Therefore, this pilot study aims to evaluate the possibility of moving to a home-based approach.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We conduct a randomized, double-blinded, sham-controlled, cross-over study of home transcranial alternating current stimulation (tACS) in patients with mild to AD. The intervention consist of daily model-driven personalized home-based tACS delivered for 8 weeks, 5 days per week (40 sessions). tACS is applied daily for 1 hour at 40 Hz on the dorsolateral prefrontal cortex and temporal cortex bilaterally.<\/jats:p>\n                  <jats:p>The outcomes are assessed at baseline, right after the intervention, and at 2 months follow-up for both conditions (Real and Sham). The primary outcomes measures are the safety and feasibility of the intervention, as well as the changes in the AD Assessment Scale Cognitive Subscale (ADAS-Cog) 13. To assess secondary outcomes, participants undergo extensive neuropsychological assessment. Finally, as exploratory outcomes, functional and structural magnetic resonance imaging (MRI), resting and evoked electroencephalography (EEG and TMS-EEG), as well as blood biomarkers to measure changes in neurodegenerative and neuroinflammatory markers, are collected. The study protocol has been approved by the local institutional review board (IRB).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>We hypothesize that the tACS treatment is safe and feasible and will result in a slower progression of cognitive decline. Moreover, we wish for a restoring of gamma power as measured by TMS-EEG, as well as a structural preservation and functional network reorganization as compared to sham treatment.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>The final goal is to obtain preliminary data in advance of a larger clinical trial to prove the possibility of treating AD patients at home through tACS.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.04.14.25325464","type":"posted-content","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T02:15:20Z","timestamp":1745115320000},"source":"Crossref","is-referenced-by-count":4,"title":["A Randomized Sham-Control Trial for Home-Based Transcranial Alternating Current Stimulation (tACS) In Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-4629","authenticated-orcid":false,"given":"Lucia","family":"Mencarelli","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-1112","authenticated-orcid":false,"given":"Martina","family":"Assogna","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0521-5555","authenticated-orcid":false,"given":"Elena","family":"Savastano","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3058-3337","authenticated-orcid":false,"given":"Ilaria","family":"Borghi","sequence":"additional","affiliation":[]},{"given":"Francesca","family":"Candeo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1780-4131","authenticated-orcid":false,"given":"Sonia","family":"Bonn\u00ec","sequence":"additional","affiliation":[]},{"given":"Francesco","family":"Di Lorenzo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1580-8750","authenticated-orcid":false,"given":"Roser","family":"Sanchez-Todo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1235-6533","authenticated-orcid":false,"given":"Ricardo","family":"Salvador","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-7427","authenticated-orcid":false,"given":"Emiliano","family":"Santarnecchi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-0177","authenticated-orcid":false,"given":"Giulio","family":"Ruffini","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6155-9439","authenticated-orcid":false,"given":"Giacomo","family":"Koch","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"issue":"1","key":"2025042200350624000_2025.04.14.25325464v1.1","doi-asserted-by":"crossref","first-page":"e12295","DOI":"10.1002\/trc2.12295","article-title":"Alzheimer\u2019s disease drug development pipeline: 2022","volume":"8","year":"2022","journal-title":"Alzheimers Dement Transl Res Clin Interv"},{"key":"2025042200350624000_2025.04.14.25325464v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.17530"},{"key":"2025042200350624000_2025.04.14.25325464v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)32205-4"},{"key":"2025042200350624000_2025.04.14.25325464v1.4","unstructured":"World Alzheimer Report 2022: Life after diagnosis: Navigating treatment, care and support. 2022 Sep 21 [cited 2025 Feb 14]; Available from: http:\/\/www.alzint.org\/resource\/world-alzheimer-report-2022\/"},{"issue":"3","key":"2025042200350624000_2025.04.14.25325464v1.5","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.brs.2021.03.007","article-title":"Exposure to gamma tACS in Alzheimer\u2019s disease: A randomized, double-blind, sham-controlled, crossover, pilot study","volume":"14","year":"2021","journal-title":"Brain Stimulat"},{"key":"2025042200350624000_2025.04.14.25325464v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26411"},{"key":"2025042200350624000_2025.04.14.25325464v1.7","doi-asserted-by":"crossref","unstructured":"Liu Y , Tang C , Wei K , Liu D , Tang K , Chen M , et al. 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