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Reversal of scopolamine‐induced deficits with a single dose of donepezil, an acetylcholinesterase inhibitor
Author(s) -
Snyder Peter J.,
Bednar Martin M.,
Cromer Jennifer R.,
Maruff Paul
Publication year - 2005
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2005.09.004
Subject(s) - donepezil , crossover study , psychomotor learning , placebo , acetylcholinesterase inhibitor , acetylcholinesterase , psychology , neuropsychology , anesthesia , medicine , cognition , pharmacology , audiology , dementia , neuroscience , chemistry , biochemistry , alternative medicine , disease , pathology , enzyme
Background To develop a more rapid screening paradigm for novel cognitive enhancers, the authors sought to determine the utility of a well‐known pharmacologic model of induced dementia (scopolamine challenge), paired with a sensitive neuropsychological test, for assessing the ability of a single oral dose of a current treatment for Alzheimer's disease (donepezil) to improve cognitive performance in healthy elderly subjects. Methods Thirty‐two (4 groups of 8) healthy elderly volunteers were put randomly into a double‐blind, placebo‐controlled, modified crossover design study. In Part 1, 16 subjects received donepezil (5 mg) or placebo separately in a crossover fashion. In Part 2, the remaining 2 groups of 8 subjects received scopolamine (0.3 mg subcutaneously) with each group then were assigned randomly to receive donepezil (5 mg) or placebo (in a crossover fashion) 3 hours postbaseline. A novel measure of visuospatial working memory and executive controls, the Groton Maze Learning Test (GMLT), was administered to each subject at baseline and at 2.5, 4, 5.5, 7, and 9 hours after dosing of donepezil. Results With scopolamine, subjects showed slower psychomotor speed, reduced accuracy and learning efficiency, and longer time required to navigate a hidden maze. Concurrent administration of donepezil significantly reversed these deficits and resulted in a faster recovery time. In addition, single doses of donepezil alone led to improved psychomotor speed, accuracy, and learning efficiency. Conclusions Robust effects of single‐dose donepezil on cognition can be readily observed, with the use of a complex hidden maze learning task, both with and without a scopolamine‐induced deficit model in healthy elderly adults.