{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:53:53Z","timestamp":1776941633794,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":301,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Scientific World Journal"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Acetylcholinesterase (AChE)\/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild\u2010moderate and moderate\u2010severe forms of Alzheimer\u2019s disease (AD), respectively. High doses of the AChE\u2010I donepezil were licensed in the USA for moderate\u2010severe AD, and the association AChE\/ChE\u2010Is plus memantine was proposed for AD at this stage. <jats:italic>Objectives<\/jats:italic>. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate\u2010severe AD. <jats:italic>Method<\/jats:italic>. Double\u2010blind, placebo\u2010controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate\u2010severe AD were reviewed. Analysis done in January 2013 considered the years 2007\u20132012. <jats:italic>Results and Conclusion<\/jats:italic>. Only 83 of the 941 papers selected were considered relevant, and only 13\u2009met the criterion of \u201cadequacy and representativeness.\u201d Memantine and donepezil lead to improvements in moderate\u2010to\u2010severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine\u2010donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24\u201352 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.<\/jats:p>","DOI":"10.1155\/2013\/925702","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T22:27:40Z","timestamp":1383085660000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Efficacy of Memantine, Donepezil, or Their Association in Moderate\u2010Severe Alzheimer\u2019s Disease: A Review of Clinical Trials"],"prefix":"10.1155","volume":"2013","author":[{"given":"Ivana","family":"Molino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Colucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angiola M.","family":"Fasanaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-4099","authenticated-orcid":false,"given":"Enea","family":"Traini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7794-4662","authenticated-orcid":false,"given":"Francesco","family":"Amenta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,10,29]]},"reference":[{"key":"e_1_2_5_1_2","unstructured":"Alzheimer\u2019s Disease Internationl World Alzheimer Report 2010: the global economic impact of dementia http:\/\/www.alz.org\/documents\/national\/World_Alzheimer_Report_2010.pdf."},{"key":"e_1_2_5_2_2","unstructured":"EMEA Committee for Medicinal Products for Human Use Plenary meeting monthly report October 2005 European Medicines Agency http:\/\/www.emea.europa.eu\/pdfs\/human\/press\/pr\/36234805en.pdf."},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000200013"},{"key":"e_1_2_5_4_2","unstructured":"National Institute for Clinical Excellence (NICE) Donepezil galantamine rivastigmine and memantine for the treatment of Alzheimer\u2019s disease NICE Technology Appraisal Guidance 2011 no. 217 National Institute for Clinical Excellence London UK (Review of NICE Technology Appraisal Guidance 111)."},{"key":"e_1_2_5_5_2","unstructured":"Institute for Quality and Efficiency in Health Care (IQWiG)andFederal Joint Committee Responder analyses on memantine in Alzheimer\u2019s disease Executive Summary of Rapid Report 2011 no. 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