{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:07:47Z","timestamp":1789780067761,"version":"4.0.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Acupuncture is used as an adjuvant therapy for Alzheimer\u2019s disease (AD), but available evidence for efficacy is limited so far. Growing studies suggest that resident gut microbiota contributes to the development and progression of AD. Meanwhile, acupuncture is reported to treat gastrointestinal and neurodegenerative disorders <jats:italic>via<\/jats:italic> the gut-brain axis. Therefore, our aim is to confirm the adjunctive therapeutic effects of acupuncture for AD, and explore the relationship between clinical efficacy and shifts of gut microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>This is a randomized, participant-masked, sham-controlled trial. One hundred and sixty participants with mild AD will be randomly assigned (1:1) to either active acupuncture or non-penetrating sham acupuncture (three times weekly for 14\u2009weeks) added to donepezil treatment (5\u2009mg per day for 28\u2009weeks). The primary efficacy outcome is the change from baseline to week 28 in the Alzheimer\u2019s disease Assessment Scale (ADAS-cog12). Secondary efficacy outcomes include other assessments of the Mini-Mental State Examination (MMSE), the Alzheimer\u2019s disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI). Gut microbiota will be measured using 16S rRNA tag sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This rigorous trial will provide high-quality evidence on the efficacy of acupuncture as adjunctive treatment for mild AD, and identify the possible mechanisms of acupuncture from gut microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>[<jats:ext-link>https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05078944<\/jats:ext-link>], <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link> [NCT05078944]. Registered 15 October 2021<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1014113","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T13:14:55Z","timestamp":1677158095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy of acupuncture in patients with mild Alzheimer\u2019s disease and its impact on gut microbiota: Study protocol for a randomized sham-controlled trial"],"prefix":"10.3389","volume":"10","author":[{"given":"Xiehe","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"ref1","volume-title":"World Alzheimer Report 2019: Attitudes to Dementia","author":"Bhatt","year":"2019"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/WAD.0b013e318065c495","article-title":"A 24-week randomized, controlled trial of Memantine in patients with moderate-to-severe Alzheimer disease","volume":"21","author":"Van Dyck","year":"2007","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1212\/wnl.50.1.136","article-title":"A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. 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