• R H Pietrzak, P Maruff, and P J Snyder.
• Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
• J Nutr Health Aging. 2009 Mar 1; 13 (3): 268-73.

ObjectivesChange in cognitive function in response to a pharmacologic challenge can be observed with greater sensitivity by employing cognitive tests with optimal psychometric properties and a statistical approach that more accurately accounts for individual variability in performance. To demonstrate this approach we examined the cognitive effects of a single acute dose administration of an acetylcholinesterase inhibitor, donepezil, in healthy older adults and in older adults with mild Alzheimer's disease (AD).DesignPlacebo-controlled crossover study with three separate testing days: baseline, placebo, and donepezil, with assessments at baseline, and 1-, 2-, 3-, 6-, and 8-hrs post-dosing on each day.SettingEarly phase I clinical trial.Participants15 healthy older adults; 14 older adults with mild Alzheimer's disease.InterventionSingle acute dose of 5mg donepezil.MeasurementsPerformance on the Groton Maze Learning Test (GMLT), a computerized neuropsychological measure of spatial working memory and error monitoring.ResultsA single acute dose of donepezil improved GMLT performance in healthy older adults (effect size: 0.83 at 6 hrs post-dosing) and older adults with mild AD (effect size: 0.58 at 3 hrs post-dosing).ConclusionThe GMLT detected cognitive improvement following a single, acute dose administration of donepezil in healthy older adults and older adults with mild AD. The choice of cognitive tests designed for repeated administration, as well as an analytic approach that emphasizes individual-level change in cognitive function, provides a sensitive approach to detecting central nervous system drug penetration and activity of cognitive-enhancing agents.

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