Quantitative analysis of the effects of donepezil on regional cerebral blood flow in Alzheimer's disease by using an automated program, 3DSRT.
BACKGROUND
Donepezil, an acetylcholinesterase inhibitor, has been reported to have an effect that improves cerebral blood flow (CBF) alongside its primary effect on memory function. The aim of this study was to investigate the effects of long-term, low-dose donepezil therapy on blood perfusion in Alzheimer's disease (AD) by using a fully automated regional CBF quantification program named 3DSRT.


METHODS
Fifteen subjects with mild to moderate AD according to NINCDS/ADRDA criteria underwent 99mTc-ethylcysteinate dimer (ECD) brain perfusion single photon emission computed tomography (SPECT) twice with an interval of 55.1 +/- 11.0 weeks. The dose of donepezil was fixed at 5 mg/day following the induction period (3 mg/day) of 2 weeks. Clinical efficacy of donepezil was assessed by using the Mini-Mental State Examination (MMSE). The results of SPECT imaging under exactly identical conditions were analyzed by 3DSRT, which enables us to perform a very objective assessment.


RESULTS
Despite a decrease of the MMSE score from 20.9 +/- 4.7 to 18.7 +/- 5.7, CBF was increased in almost all cerebral areas except the left temporal segment. The increase was statistically significant in the left callosomarginal, right central, and bilateral pericallosal and lenticular nucleus segments.


CONCLUSIONS
Thus far, no direct cerebrovascular effects have been reported for donepezil. We hypothesize that these CBF-promoting effects of donepezil might be related to increased neuronal activity and enhanced connection of neurons.
Tateno
Masaru
M
Department of Neuropsychiatry, Sapporo Medical University, South-1, West-16, Sapporo, Hokkaido, 0608543, Japan. tatema@sapmed.ac.jp
Kobayashi
Seiju
S
Utsumi
Kumiko
K
Morii
Hidetoshi
H
Fujii
Kazuki
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil