Do cholinesterase inhibitors prolong the survival of patients with mild-to-moderate Alzheimer's disease?

Abstract

Cholinesterase inhibitors (ChEI) are used to treat Alzheimer's dementia (AD) in many countries. In animal studies it was shown that donepezil has an influence on the survival of mice and rats with chronic heart failure. In the last years there was some evidence that even in humans ChEI may have a favourable effect on survival and cardiovascular death. PubMed was searched for double-blind, randomized, placebo-controlled studies with donepezil and galantamine with more than 100 patients with mild to moderate Alzheimer's dementia which reported the number of deaths. The odds ratio was then calculated for studies up to six months, 6 months to one year and above one year. For donepezil patients survival was better than placebo in the studies up to six months (relative risk verum/placebo: 0.35). After one year the relative risk was about on the placebo level (1.01) and after two years numerically worse than for placebo (1.27). For galantamine survival was also numerically better in the studies 3-6 months (relative risk verum/placebo: 0.71) and was still better after two years (0.59). Only in one of those studies mortality was a primary end point. The ChEI have a systemic effect which exceeds the pure cognitive ameliorations and which is perhaps associated with different survival rates in humans. This may be drug dependent and may play a role in the choice of the ChEI for a patient. Further long-term studies would be necessary to further assess this question.