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Acetylcholinesterase Inhibitor in Combination With Cognitive Training in Older Adults

¹ Palo Alto Veterans Affairs Health Care System, Palo Alto, California.
² Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.

Address correspondence to Jerome A. Yesavage, MD, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5550. E-mail: yesavage{at}stanford.edu.

To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.

Key Words: Acetylcholinesterase inhibitor • Cognitive training • Donepezil