OBJECTIVES: 6.7 million Americans 65 and older will have Alzheimer's by 2023. 73% of the population is 75 years or older. The projected frequency of AD worldwide in 2050 is 12.7 million. Most studies of drug treatment for Alzheimer's focus on mild-to-moderate symptoms, with little guidance for severe symptoms. We studied whether donepezil, galantamine, rivastigmine, or memantine are cost-effective for community-dwelling patients with mild-to-moderate or moderate-to-severe Alzheimer's in the US.

METHODS: 295 community-dwelling patients with moderate/severe Alzheimer's disease already on donepezil were randomized to (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine; (v) continue galantamine; (vi) discontinue galantamine; (vii) discontinue galantamine and start memantine; or (viii) continue galantamine and start memantine; (ix) continue rivastigmine; (x) discontinue rivastigmine; (xi) discontinue rivastigmine and start memantine; or (xii) continue rivastigmine and start memantine in a 52-week, double-blind, placebo-controlled, factorial clinical trial.

RESULTS: Continuing donepezil for 52 weeks (about 12 months) was more cost-effective than discontinuation and starting memantine was more cost-effective than donepezil discontinuation. Donepezil–memantine combined is not more cost-effective than donepezil alone, considering cognition, activities of daily living, and health-related quality of life.

CONCLUSIONS: Strong evidence to improve patient outcomes and efficiently use resources now exists to guide clinical decisions and commissioning for mild-to-moderate and moderate-to-severe AD patients.