{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:54:56Z","timestamp":1791046496145,"version":"4.1.0"},"reference-count":54,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) remains a therapeutic challenge, and adding other agents to donepezil may offer additional benefits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This network meta-analysis aimed to compare the efficacy of donepezil-based combination therapies versus donepezil monotherapy in patients with AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase, Cochrane Library and Web of Science up to October 2025 for randomized-controlled trials comparing donepezil plus another drug with donepezil alone. The primary outcomes were cognitive function [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale\u2013Cognitive Subscale (ADAS-cog)], behavioral function (Neuropsychiatric Inventory) and functional ability [Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)]. A frequentist network meta-analysis was performed, and treatments were ranked by SUCRA (Surface under the cumulative ranking curve) values. Time-stratified analyses were also conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>41 trials involving 9822 patients were included. Compared with placebo, several combinations significantly improved MMSE and ADAS-cog scores, with Don (Donepezil)\u2009+\u2009Mas (Masitinib) (97.5%, 92.9%), Don\u2009+\u2009NBP (DL-3-n-butylphthalide) (82.5%, 74.5%) and Don\u2009+\u2009DSC (Dengzhan shengmai capsule) (81.4%) ranking highest. For ADCS-ADL, Don\u2009+\u2009Mas (92.7%), Don\u2009+\u2009NBP (74.1%), and Don\u2009+\u2009DSC (77.1%) showed significant improvements. No combination was statistically superior to donepezil monotherapy for any outcome, but numerical trends favored combination therapy across all time windows. The certainty of evidence was mostly moderate to low.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Several donepezil-based combination therapies, particularly those with masitinib, NBP, DSC, and memantine, are more effective than placebo in improving cognitive and functional outcomes in AD. Although direct comparisons with donepezil monotherapy did not reach statistical significance, consistent trends support the potential of add-on strategies. Longer-term trials are needed to confirm sustained benefits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261491977","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:15:32Z","timestamp":1790828132000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The efficacy of donepezil combination therapy strategies in Alzheimer's disease: A systematic review and network meta-analysis"],"prefix":"10.1177","author":[{"given":"Xinyue","family":"Ning","sequence":"first","affiliation":[{"name":"Shenyang Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Xiao","sequence":"additional","affiliation":[{"name":"The 964th Hospital of PLA Joint Logistic Support Force No. 4799, Lvyuan District, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"General Hospital of Northern Theater Command"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Jiao","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhu","family":"Li","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-2906","authenticated-orcid":false,"given":"Yingshi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-9971","authenticated-orcid":false,"given":"Qingchun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University"},{"name":"General Hospital of Northern Theater Command"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000551382"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-024-08815-z"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215680"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.071014"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16499-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251378354"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2024.105273"},{"key":"e_1_3_3_10_2","article-title":"PRISMA 2020 Explanation and elaboration: updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page MJ","year":"2021","unstructured":"Page MJ, Moher D, Bossuyt PM, et al. 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