TITLE

Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease

AUTHOR(S)
Bohnen, N. I.; Kaufer, D. I.; Hendrickson, R.; Ivanco, L. S.; Lopresti, B. J.; Koeppe, R. A.; Meltzer, C. C.; Constantine, G.; Davis, J. G.; Mathis, C. A.; DeKosky, S. T.; Moore, R. Y.
PUB. DATE
March 2005
SOURCE
Journal of Neurology, Neurosurgery & Psychiatry;Mar2005, Vol. 76 Issue 3, p315
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
Objectives: 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.
ACCESSION #
16911283

 

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