Background/Aims: Donepezil is an acetylcholinesterase inhibitor used to treat Alzheimer's disease (AD). In this study, we used a voxel-based specific regional analysis system for AD (VSRAD) to analyze the hippocampal volume and to assess the pharmacologic effects of donepezil as a disease modifier. Methods: A total of 185 AD patients underwent MRI, 120 (43 men and 77 women, 77.8 ± 7.1 years) without and 65 (29 men and 36 women, 78.4 ± 6.0 years) with donepezil treatment. VSRAD was compared in both groups and against a database of 80 normal subjects. The Z-score was used to assess the degree of hippocampal atrophy. Results: No significant difference between the groups was found for age, sex, or Z-scores, but a significant difference was found for mean Mini-Mental State Examination (MMSE) scores (p = 0.02, Student's t test). Single regression analysis showed no significant association between Z-scores and MMSE scores in the treated group (p = 0.494), but a significant association in the untreated group (p = 0.001) was observed. This implies that the MMSE score becomes lower when the Z-score is higher in the untreated group, whereas there is no significant trend in the treated group. Conclusion: Donepezil affects the relationship between hippocampal volume and cognitive function and may therefore have a pharmacologic effect as a disease modifier.

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