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Methodological improvements in quantifying cognitive change in clinical trials: an example with single-dose administration of donepezil


Pietrzak, R. H., Maruff, P., Snyder, P. J.


The Journal Of Nutrition, Health & Aging, Volume: 13, No.: 3, Pages.: 268-273

Year of Publication



Objectives: Change 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).; Design: Placebo-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.; Setting: Early phase I clinical trial.; Participants: 15 healthy older adults; 14 older adults with mild Alzheimer’s disease.; Intervention: Single acute dose of 5mg donepezil.; Measurements: Performance on the Groton Maze Learning Test (GMLT), a computerized neuropsychological measure of spatial working memory and error monitoring.; Results: A 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).; Conclusion: The 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.;


administration & dosage, aged, alzheimer disease, cholinesterase inhibitors, cognition, cognition disorders, complications, diagnosis, donezepil, double-blind method, drug effects, drug therapy, etiology, humans, indans, male, maze learning, middle aged, neuropsychological tests, piperidines, psychometrics, reproducibility of results, research design, sensitivity and specificity, statistics & numerical data, therapeutic use

Countries of Study


Types of Dementia

Alzheimer’s Disease, Mild Cognitive Impairment (MCI)

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime