Title: P4–337: Cognition and long term donepezil use in Alzheimer's disease
Abstract: Short to mid term donepezil use is known as an effective treatment for Alzheimer's disease (AD) patients. Two open–label trials were available for the effect of the long–term use. The results of these studies were favorable to the long–term effect of donepezil. However, the effect of long–term donepezil use in AD is now questioned by the study of AD2000 collaborative group. They expressed disappointingly small benefits from donepezil use both in global and cognitive function. The discrepancy in these contradicted reports must be prudently reconsidered before we reach the final conclusion. We tried to consider how the conflicting results occurred and to reveal the influential factors for the cognitive decline and the effect of long term donepezil use. We conducted a retrospective study to see the effects of long–term donepezil use on cognitive functioning. We compared the pattern of cognitive change between two groups, well–characterized AD patients followed in our clinics from 1994 to 1999 before donepezil and the patients followed from 2000 to 2003 with donepezil using a mixed effect model. Global cognitive function was assessed by Mini Mental State Examination (MMSE) at 6 months interval up to 24 months. We conducted sensitivity analysis to avoid overt and hidden bias, such as the effect of the different social backgrounds and diagnostic mistakes. The annual declines between two groups were statistically significant (P < 0.001) in the mixed effect model, and these results remain unchanged by the sensitivity analysis. Overall longitudinal pattern of cognitive change in donepezil users appears to be similar with the previous trials. In contrast, the pattern differed from the result of AD2000, although the pattern looked similar to other studies. Difference of the cognitive decline in the placebo group might cause the contradiction. The discrepancy between these studies against the AD2000 group should be discussed more prudently.