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dc.contributor.authorHoward, R
dc.contributor.authorMcShane, R
dc.contributor.authorLindesay, J
dc.contributor.authorRitchie, C
dc.contributor.authorBaldwin, A
dc.contributor.authorBarber, R
dc.contributor.authorBurns, A
dc.contributor.authorDening, T
dc.contributor.authorFindlay, D
dc.contributor.authorHolmes, C
dc.contributor.authorJones, R
dc.contributor.authorJones, R
dc.contributor.authorMcKeith, I
dc.contributor.authorMacharouthu, A
dc.contributor.authorO'Brien, J
dc.contributor.authorSheehan, B
dc.contributor.authorJuszczak, E
dc.contributor.authorKatona, C
dc.contributor.authorHills, R
dc.contributor.authorKnapp, M
dc.contributor.authorBallard, C
dc.contributor.authorBrown, RG
dc.contributor.authorBanerjee, Sube
dc.contributor.authorAdams, J
dc.contributor.authorJohnson, T
dc.contributor.authorBentham, P
dc.contributor.authorPhillips, PPJ
dc.date.accessioned2020-05-12T09:25:03Z
dc.date.available2020-05-12T09:25:03Z
dc.date.issued2015-12
dc.identifier.issn1474-4422
dc.identifier.issn1474-4465
dc.identifier.urihttp://hdl.handle.net/10026.1/15665
dc.description.abstract

BACKGROUND: Findings from observational studies have suggested a delay in nursing home placement with dementia drug treatment, but findings from a previous randomised trial of patients with mild-to-moderate Alzheimer's disease showed no effect. We investigated the effects of continuation or discontinuation of donepezil and starting of memantine on subsequent nursing home placement in patients with moderate-to-severe Alzheimer's disease. METHODS: In the randomised, double-blind, placebo-controlled Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial, community-living patients with moderate-to-severe Alzheimer's disease (who had been prescribed donepezil continuously for at least 3 months at a dose of 10 mg for at least the previous 6 weeks and had a score of between 5 and 13 on the Standardised Mini-Mental State Examination) were recruited from 15 secondary care memory centres in England and Scotland and randomly allocated to continue donepezil 10 mg per day without memantine, discontinue donepezil without memantine, discontinue donepezil and start memantine 20 mg per day, or continue donepezil 10 mg per day and start memantine 20 mg per day, for 52 weeks. After 52 weeks, choice of treatment was left to participants and their physicians. Place of residence was recorded during the first 52 weeks of the trial and then every 26 weeks for a further 3 years. A secondary outcome of the trial, reported in this study, was nursing home placement: an irreversible move from independent accommodation to a residential caring facility. Analyses restricted to risk of placement in the first year of follow-up after the patients had completed the double-blind phase of the trial were post-hoc. The DOMINO-AD trial is registered with the ISRCTN Registry, number ISRCTN49545035. FINDINGS: Between Feb 11, 2008, and March 5, 2010, 73 (25%) patients were randomly assigned to continue donepezil without memantine, 73 (25%) to discontinue donepezil without memantine, 76 (26%) to discontinue donepezil and start memantine, and 73 (25%) to continue donepezil and start memantine. 162 (55%) patients underwent nursing home placement within 4 years of randomisation, with similar numbers for all groups (36 [49%] in patients who continued donepezil without memantine, 42 [58%] who discontinued donepezil without memantine, 41 [54%] who discontinued donepezil and started memantine, and 43 [59%] who continued donepezil and started memantine). We noted significant (p=0·010) heterogeneity of treatment effect over time, with significantly more nursing home placements in the combined donepezil discontinuation groups during the first year (hazard ratio 2·09 [95% CI 1·29-3·39]) than in the combined donepezil continuation groups, and no difference during the next 3 years (0·89 [0·58-1·35]). We noted no effect of patients starting memantine compared with not starting memantine during the first year (0·92 [0·58-1·45]) or the next 3 years (1·23 [0·81-1·87]). INTERPRETATION: Withdrawal of donepezil in patients with moderate-to-severe Alzheimer's disease increased the risk of nursing home placement during 12 months of treatment, but made no difference during the following 3 years of follow-up. Decisions to stop or continue donepezil treatment should be informed by potential risks of withdrawal, even if the perceived benefits of continued treatment are not clear. FUNDING: Medical Research Council and UK Alzheimer's Society.

dc.format.extent1171-1181
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoeng
dc.publisherElsevier BV
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAlzheimer Disease
dc.subjectCognition
dc.subjectDonepezil
dc.subjectDouble-Blind Method
dc.subjectFemale
dc.subjectHomes for the Aged
dc.subjectHumans
dc.subjectIndans
dc.subjectMale
dc.subjectMemantine
dc.subjectNeuropsychological Tests
dc.subjectNootropic Agents
dc.subjectNursing Homes
dc.subjectPiperidines
dc.subjectSeverity of Illness Index
dc.titleNursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: secondary and post-hoc analyses
dc.typejournal-article
dc.typeJournal Article
dc.typeRandomized Controlled Trial
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000364855100012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue12
plymouth.volume14
plymouth.publication-statusPublished
plymouth.journalThe Lancet Neurology
dc.identifier.doi10.1016/s1474-4422(15)00258-6
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School/PMS - Manual
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA03 Allied Health Professions, Dentistry, Nursing and Pharmacy
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeEngland
dcterms.dateAccepted2015-09-25
dc.identifier.eissn1474-4465
dc.rights.embargoperiodNot known
rioxxterms.funderMedical Research Council
rioxxterms.identifier.projectDonepezil and memantine in moderate to severe Alzheimers disease - The DOMINO-AD Trial
rioxxterms.versionofrecord10.1016/s1474-4422(15)00258-6
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-12
rioxxterms.typeJournal Article/Review
plymouth.funderDonepezil and memantine in moderate to severe Alzheimers disease - The DOMINO-AD Trial::Medical Research Council


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