Objective: To review studies pertinent to the question of whether to treat moderate to severe Alzheimer's disease (AD) with a cholinesterase inhibitor (ChEI); and then to briefly present a critical appraisal of available information on the relevant benefits, risks, and costs.
Design: A two stage review: First, a review of random controlled trials. Second, a limited review of other studies.
Materials and Methods: Online searches were performed on the following data bases: Clinical Evidence, ACP Journal Club, Database of Abstracts of Reviews of Effectiveness (DARE), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials. Then Current Contents, PsychINFO, and Medline were searched for the period 2000 through third quarter of 2002. The initial search terms were "cholinesterase AND (Alzheimers OR dementia)". The titles of the articles thus retrieved were further searched for the words "severe" (which included "moderate to severe") or the word "nursing home" and for those references retrieved, the abstracts or full articles were obtained, reviewed, and analyzed.
Results: Three published random controlled studies were identified. Study 1: donepezil vs placebo; Study 2: rivastigmine vs placebo; Study 3: donepezil vs placebo. Subjects for Studies 1 (n=290) and 2 (n=2105) resided in the community or assisted living facilities; subjects for Study 3 (n=208) resided in nursing homes. Baseline severity ratings were, respectively, Study 1: s-MMSE mean 11.8, (range 5-18); Study 2: Global Deterioration Scale greater than or equal to 5 ("moderately severe") 29% of subjects; Study 3: MMSE mean 14.4, (range 5-26), 25% of subjects less than 10. Significant benefits were found for cognition in all three studies; for ADL functions in Studies 1 and 2; and for behavioral & psychological symptoms of dementia (BPSD) in Study 1. Non-completion of trials associated with adverse events in Study 1 and Study 3 were reported, respectively, as 6-20% for placebo subjects and 8-13% for ChEI subjects. The issue of cost was not addressed in these trials. The results of other studies were surveyed. Generally it was reported that ChEIs benefit patients in regard to cognition and/or ADL function and/or BPSD; side effects were mild to moderate and further reduced by gradual titration of dose increases. There are reports that treatment with ChEIs may prevent or delay the emergence of BPSD, as well as treat them, and thereby reduce the use of antipsychotics and benzodiazepines along with their troublesome side effects. ChEIs may be cost effective through reducing patient distress, lessening the care burden, and delaying placement in nursing homes, but prospective controlled data are needed. A retrospective controlled study found that users of tacrine had a lower mortality rate than matched non-users.
Conclusion: While more research is needed, the reports so far indicate that ChEIs may benefit people with moderate to severe AD, both directly and indirectly, and may be worth the cost.
Back to Poster Session 1
Back to Oral and Poster Sessions
Back to The IPA European Regional Meeting (1-4 April 2003) of IPA