Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease.

Objective: The objective of this study was to elucidate the relationship between the effects of donepezil hydrochloride (donepezil) and cerebral blood flow, and to evaluate the usefulness of cerebral blood flow imaging in assessing and predicting treatment effectiveness.

Methods: The subjects were 29 outpatients (12 men and 17 women; age 50-82 years; mean age 69.2 years), who had received a diagnosis of Alzheimer's disease (AD). Efficacy was evaluated before donepezil administration; after 1 month, 3 months, and 6 months of drug administration; and at 1 year after completion of administration using the Japanese version of the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog), as a measure of cognitive function. The ADAS-cog has been frequently used to evaluate cognitive function in AD patients. Patients whose ADAS-cog scores improved by 3 or more points during the observation period were classified as responders, and those with no improvement were classified as nonresponders. (123)I-IMP was used for single photon emission computed tomography cerebral blood flow scintigraphy.

Results: On the basis of ADAS-cog score improvement, 22 of the 29 patients were responders (7 men and 15 women; age 50-82 years; mean age 69.0 years) and seven were nonresponders (5 men and 2 women; age 61-80 years; mean age 70.0 years). The results indicate that a difference in cerebral blood flow responsiveness after 1 month of treatment distinguishes responders from nonresponders. After 1 month, blood flow was significantly decreased in all regions of nonresponders, whereas significant increases in blood flow were seen in the anterior frontal lobe and parietal lobe of responders. At that time point, blood flow in the basal ganglion differed significantly between the two groups, indicating that this difference in responsiveness after 1 month of treatment may distinguish responders from nonresponders.

Conclusions: In cognitive function testing, the group that exhibited a complete response showed improvement primarily in parameters reflecting frontal lobe function. Complete responders also showed significantly greater blood flow increases in the basal ganglion and thalamus early during the treatment period. This indicates that the drug responsiveness of the basal ganglion and thalamus affects frontal lobe function and distinguishes complete responders from patients who do not exhibit such a response.