Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease.
OBJECTIVE
To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy.


METHODS
Cognitive and N-[(11)C]methyl-piperidin-4-yl propionate ([(11)C]PMP) AChE positron emission tomography (PET) assessments before and after donepezil therapy.


RESULTS
Analysis of the PET data revealed mean (temporal, parietal, and frontal) cortical donepezil induced AChE inhibition of 19.1% (SD 9.4%) (t = -7.9; p<0.0001). Enzyme inhibition was most robust in the anterior cingulate cortex (24.2% (6.9%), t = -14.1; p<0.0001). Donepezil induced cortical inhibition of AChE activity correlated with changes in the Stroop Color Word interference scores (R(2) = 0.59, p<0.01), but not with primary memory test scores. Analysis of the Stroop test data indicated that subjects with AChE inhibition greater than the median value (>22.2%) had improved scores on the Stroop Color Word Test compared with subjects with less inhibition who had stable to worsening scores (t = -2.7; p<0.05).


CONCLUSIONS
Donepezil induced inhibition of cortical AChE enzyme activity is modest in patients with mild AD. The degree of cortical enzyme inhibition correlates with changes in executive and attentional functions.
Bohnen
N I
NI
University of Pittsburgh, Liliane S Kaufmann Building, Suite 811, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA. nbohnen@pitt.edu
Kaufer
D I
DI
Hendrickson
R
R
Ivanco
L S
LS
Lopresti
B J
BJ
Koeppe
R A
RA
Meltzer
C C
CC
Constantine
G
G
Davis
J G
JG
Mathis
C A
CA
Dekosky
S T
ST
Moore
R Y
RY
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D001288:Attention / Q000187:drug effects; D002540:Cerebral Cortex / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D049268:Positron-Emission Tomography
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D000110:Acetylcholinesterase
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