Donepecilo

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

original article

Donepezil and Memantine
for Moderate-to-Severe Alzheimer’s Disease
Robert Howard, M.D., Rupert McShane,F.R.C.Psych., James Lindesay, D.M.,
Craig Ritchie, M.D., Ph.D., Ashley Baldwin, M.R.C.Psych., Robert Barber, M.D.,
Alistair Burns, F.R.C.Psych., Tom Dening, F.R.C.Psych., David Findlay, M.B., Ch.B.,
CliveHolmes, Ph.D., Alan Hughes, M.B., Ch.B., Robin Jacoby, D.M.,
Rob Jones, M.B., Ch.B., Roy Jones, M.B., Ian McKeith, F.Med.Sc.,
Ajay Macharouthu, M.R.C.Psych., John O’Brien, D.M., Peter Passmore,M.D.,
Bart Sheehan, M.D., Edmund Juszczak, M.Sc., Cornelius Katona, M.D.,
Robert Hills, D.Phil., Martin Knapp, Ph.D., Clive Ballard, M.D., Richard Brown, Ph.D.,
Sube Banerjee, M.D., Caroline Onions,P.G.Dip., Mary Griffin, R.G.N.,
Jessica Adams, B.Sc., Richard Gray, M.Sc., Tony Johnson, Ph.D.,
Peter Bentham, M.B., Ch.B., and Patrick Phillips, Ph.D.

A bs t r ac t
Background

Clinical trialshave 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 tomoderate-to-severe disease.
Methods

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 5to 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, discontinuedonepezil, 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
onthe 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...