Is donepezil therapy associated with reduced mortality in nursing home residents with dementia?

Since cholinesterase inhibitors (CEIs) were approved for use in mild to moderate Alzheimer's disease, the therapeutic efficacy of this class of medications has largely centered on demonstration of short-term improvement in cognition and global function. Later evidence suggested that the beneficial effects of CEIs might be sustainable for at least 3 years and that CEIs may have a disease-modifying effect on Alzheimer's disease. These broad-ranging, long-term effects may explain the recent finding that the use of a CEI among nursing home residents with dementia was associated with lower mortality.

The goal of this study was to investigate whether donepezil treatment is associated with reduced mortality in nursing home residents who have dementia.

We performed a retrospective matched cohort study using the Systematic Assessment of Geriatric Drug Use via Epidemiology database, which contains data collected with the Minimum Data Set on a cross section of 915,469 nursing home residents aged > 65 years between 1998 and 2000 in 6 US states. We identified users of donepezil (5 and 10 mg) and an equal number of matched nonusers in the same facility, date of donepezil use, level of cognitive function, and dementia diagnosis. Comparisons of the 2 groups were made for sociodemographic variables, dementia severity, number of medications, and major comorbid illnesses (heart disease, cancer, diabetes mellitus, chronic obstructive pulmonary disease, and malnutrition), as well as survival over the 2-year study period.

A total of 5423 users and 5423 nonusers of donepezil were identified. Based on Cox proportional hazards models, donepezil users showed a lower mortality rate than nonusers. The hazard rate ratio was 0.89 (95% CI, 0.83-0.95). After adjusting for the confounding variables, sociodemographic factors, other psychotropic drugs, and comorbid conditions, this survival advantage remained (hazard rate ratio, 0.90; 95% CI, 0.84-0.96).

A relationship was observed between treatment of nursing home residents with donepezil and lower mortality. If the relationship was due to a direct effect of donepezil use, then this observation has implications for the socioeconomic impact of CEI therapy in those with advanced dementia in the nursing home. These implications deserve future investigation.