Cholinesterase Inhibitors and Memantine in More Advanced Alzheimer’s Disease: The Debate Continues

Evaluation of: Howard R, McShane R, Lindesay J et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 366 (10), 893–903 (2012). A large randomized controlled study was designed to evaluate whether community-living patients with moderate-to-severe Alzheimer’s disease currently receiving donepezil would benefit from continuing this treatment, and whether initiating therapy with memantine at this point was beneficial. In the predominantly white female study population (mean age 77 years) comprising 295 community-dwelling patients, statistically significant cognitive and functional benefits of continuing treatment with donepezil for patients with moderate-to-severe Alzheimer’s disease over a period of 52 weeks were found. Combination therapy with donepezil and memantine conferred no extra benefit to the cognitive and functional status of the subjects, although memantine therapy was associated with fewer behavioral and psychological symptoms. Further studies are required to clarify whether these agents are clinically beneficial in moderate-to-severe Alzheimer’s disease.