Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study.
OBJECTIVE
The authors evaluated the effects of donepezil (10 mg/day) versus placebo on brain glucose metabolism.


METHODS
This was a randomized, double-blind, parallel-group, 24-week pilot study in 28 patients with mild-to-moderate Alzheimer disease (AD). Functional brain activity was quantified by measuring average glucose metabolism in an axial brain slice and regional brain glucose metabolism using positron emission tomography.


RESULTS
At Week 24, relative to the pons metabolic rate, mean brain glucose metabolism in an axial slice at the level of the striatum was maintained within 0.5% of mean baseline levels for donepezil-treated patients, whereas it declined by an average of 10.4% in placebo-treated patients. This observation was confirmed by an analysis of differences in the mean slopes of glucose metabolism in the striatal slice in donepezil- and placebo-treated patients during the 24-week period. Significant treatment differences at Week 24 favoring donepezil for the mean percentage change from baseline in regional brain glucose metabolism were observed in four predefined regions of interest: the right parietal lobe 1, left temporal lobe 2, right frontal lobe 2, and left frontal lobe 2.


CONCLUSIONS
Placebo-treated patients with AD show a decline in functional brain activity, relative to the pons, in several regions, and treatment with donepezil may slow this decline.
Tune
Larry
L
Wesley Woods Center at Emory University, Atlanta, GA, USA. ltune@emory.edu
Tiseo
Paul J
PJ
Ieni
John
J
Perdomo
Carlos
C
Pratt
Raymond D
RD
Votaw
John R
JR
Jewart
R D
RD
Hoffman
John M
JM
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010865:Pilot Projects; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D014055:Tomography, Emission-Computed
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000077265:Donepezil; D005947:Glucose