Donepezil and life expectancy in Alzheimer's disease: A retrospective analysis in the Tajiri Project

Background: Cholinesterase inhibitors (ChEIs) such as donepezil have the effect of delaying progression of Alzheimer's disease (AD), but their effect on life expectancy is unclear. We analyzed the influence of donepezil on life expectancy after onset of AD, together with the effects of antipsychotic drugs and residency in a nursing home. Methods: All outpatients at the Tajiri Clinic from 1999-2012 with available medical records and death certificates were included in a retrospective analysis. The entry criteria were a dementia diagnosis based on DSM-IV criteria and diagnosis of AD using NINCDS-ADRDA criteria; medical treatment for more than 3 months; and follow up until less than 1 year before death. Results: We identified 390 subjects with medical records and death certificates, of whom 275 had a diagnosis of dementia that met the entry criteria. Of 100 patients diagnosed with AD, 52 had taken donepezil and 48 patients had not received the drug due to treatment prior to the introduction of donepezil in 1999 in Japan. The lifetime expectancies after onset were 7.9 years in the donepezil group and 5.3 years in the non-donepezil group. There was a significant drug effect with a significant covariate effect of nursing home residency. Other covariates did not reach a significant level. Conclusions: Although this report has the limitation of all retrospective analyses: the lack of randomization, we found a positive effect of donepezil on lifetime expectancy after onset of AD. This may be due to a decreased mortality rate caused by reduction of concomitant diseases such as pneumonia. The similar life expectancies in patients taking donepezil at home and those not taking donepezil in a nursing home indicated a positive health economic effect of the drug.