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Donepezil and Memantine for moderate-to-severe Alzheimer's Disease

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Donepezil and Memantine for moderate-to-severe Alzheimer's Disease. / Howard, Robert; McShane, Rupert; Lindesay, James; Ritchie, Craig; Baldwin, Ashley; Barber, Robert; Burns, Alistair; Dening, Tom; Findlay, David; Holmes, Clive; Hughes, Alan; Jacoby, Robin; Jones, Rob; Jones, Roy; McKeith, Ian; Macharouthu, Ajay; O'Brien, John; Passmore, Peter; Sheehan, Bart; Juszczak, Edmund; Katona, Cornelius; Hills, Robert; Knapp, Martin; Ballard, Clive; Brown, Richard; Banerjee, Sube; Onions, Caroline; Griffin, Mary; Adams, Jessica; Gray, Richard; Johnson, Tony; Bentham, Peter; Phillips, Patrick.

In: New England Journal of Medicine, Vol. 366, No. 10, 2012, p. 893-903.

Research output: Contribution to journalArticle

Harvard

Howard, R, McShane, R, Lindesay, J, Ritchie, C, Baldwin, A, Barber, R, Burns, A, Dening, T, Findlay, D, Holmes, C, Hughes, A, Jacoby, R, Jones, R, Jones, R, McKeith, I, Macharouthu, A, O'Brien, J, Passmore, P, Sheehan, B, Juszczak, E, Katona, C, Hills, R, Knapp, M, Ballard, C, Brown, R, Banerjee, S, Onions, C, Griffin, M, Adams, J, Gray, R, Johnson, T, Bentham, P & Phillips, P 2012, 'Donepezil and Memantine for moderate-to-severe Alzheimer's Disease' New England Journal of Medicine, vol 366, no. 10, pp. 893-903.

APA

Howard, R., McShane, R., Lindesay, J., Ritchie, C., Baldwin, A., Barber, R., Burns, A., Dening, T., Findlay, D., Holmes, C., Hughes, A., Jacoby, R., Jones, R., Jones, R., McKeith, I., Macharouthu, A., O'Brien, J., Passmore, P., Sheehan, B., Juszczak, E., Katona, C., Hills, R., Knapp, M., Ballard, C., Brown, R., Banerjee, S., Onions, C., Griffin, M., Adams, J., Gray, R., Johnson, T., Bentham, P., & Phillips, P. (2012). Donepezil and Memantine for moderate-to-severe Alzheimer's Disease. New England Journal of Medicine, 366(10), 893-903

Vancouver

Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R et al. Donepezil and Memantine for moderate-to-severe Alzheimer's Disease. New England Journal of Medicine. 2012;366(10):893-903.

Author

Howard, Robert; McShane, Rupert; Lindesay, James; Ritchie, Craig; Baldwin, Ashley; Barber, Robert; Burns, Alistair; Dening, Tom; Findlay, David; Holmes, Clive; Hughes, Alan; Jacoby, Robin; Jones, Rob; Jones, Roy; McKeith, Ian; Macharouthu, Ajay; O'Brien, John; Passmore, Peter; Sheehan, Bart; Juszczak, Edmund; Katona, Cornelius; Hills, Robert; Knapp, Martin; Ballard, Clive; Brown, Richard; Banerjee, Sube; Onions, Caroline; Griffin, Mary; Adams, Jessica; Gray, Richard; Johnson, Tony; Bentham, Peter; Phillips, Patrick / Donepezil and Memantine for moderate-to-severe Alzheimer's Disease.

In: New England Journal of Medicine, Vol. 366, No. 10, 2012, p. 893-903.

Research output: Contribution to journalArticle

Bibtex - Download

@article{cced0e12ad1a4a9c9fa40d8fc88f2034,
title = "Donepezil and Memantine for moderate-to-severe Alzheimer's Disease",
author = "Robert Howard and Rupert McShane and James Lindesay and Craig Ritchie and Ashley Baldwin and Robert Barber and Alistair Burns and Tom Dening and David Findlay and Clive Holmes and Alan Hughes and Robin Jacoby and Rob Jones and Roy Jones and Ian McKeith and Ajay Macharouthu and John O'Brien and Peter Passmore and Bart Sheehan and Edmund Juszczak and Cornelius Katona and Robert Hills and Martin Knapp and Clive Ballard and Richard Brown and Sube Banerjee and Caroline Onions and Mary Griffin and Jessica Adams and Richard Gray and Tony Johnson and Peter Bentham and Patrick Phillips",
year = "2012",
volume = "366",
number = "10",
pages = "893--903",
journal = "New England Journal of Medicine",
issn = "0028-4793",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Donepezil and Memantine for moderate-to-severe Alzheimer's Disease

A1 - Howard,Robert

A1 - McShane,Rupert

A1 - Lindesay,James

A1 - Ritchie,Craig

A1 - Baldwin,Ashley

A1 - Barber,Robert

A1 - Burns,Alistair

A1 - Dening,Tom

A1 - Findlay,David

A1 - Holmes,Clive

A1 - Hughes,Alan

A1 - Jacoby,Robin

A1 - Jones,Rob

A1 - Jones,Roy

A1 - McKeith,Ian

A1 - Macharouthu,Ajay

A1 - O'Brien,John

A1 - Passmore,Peter

A1 - Sheehan,Bart

A1 - Juszczak,Edmund

A1 - Katona,Cornelius

A1 - Hills,Robert

A1 - Knapp,Martin

A1 - Ballard,Clive

A1 - Brown,Richard

A1 - Banerjee,Sube

A1 - Onions,Caroline

A1 - Griffin,Mary

A1 - Adams,Jessica

A1 - Gray,Richard

A1 - Johnson,Tony

A1 - Bentham,Peter

A1 - Phillips,Patrick

AU - Howard,Robert

AU - McShane,Rupert

AU - Lindesay,James

AU - Ritchie,Craig

AU - Baldwin,Ashley

AU - Barber,Robert

AU - Burns,Alistair

AU - Dening,Tom

AU - Findlay,David

AU - Holmes,Clive

AU - Hughes,Alan

AU - Jacoby,Robin

AU - Jones,Rob

AU - Jones,Roy

AU - McKeith,Ian

AU - Macharouthu,Ajay

AU - O'Brien,John

AU - Passmore,Peter

AU - Sheehan,Bart

AU - Juszczak,Edmund

AU - Katona,Cornelius

AU - Hills,Robert

AU - Knapp,Martin

AU - Ballard,Clive

AU - Brown,Richard

AU - Banerjee,Sube

AU - Onions,Caroline

AU - Griffin,Mary

AU - Adams,Jessica

AU - Gray,Richard

AU - Johnson,Tony

AU - Bentham,Peter

AU - Phillips,Patrick

PY - 2012

Y1 - 2012

N2 - <p>BACKGROUND</p><p>Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.</p><p>METHODS</p><p>We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.</p><p>RESULTS</p><p>Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P&lt;0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P&lt;0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.</p><p>CONCLUSIONS</p><p>In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U. K. Medical Research Council and the U. K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.)</p>

AB - <p>BACKGROUND</p><p>Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.</p><p>METHODS</p><p>We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.</p><p>RESULTS</p><p>Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P&lt;0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P&lt;0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.</p><p>CONCLUSIONS</p><p>In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U. K. Medical Research Council and the U. K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.)</p>

UR - http://www.nejm.org/doi/full/10.1056/NEJMoa1106668

M1 - Article

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 10

VL - 366

SP - 893

EP - 903

ER -

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