Does the cholinesterase inhibitor, donepezil, benefit both declarative and non-declarative processes in mild to moderate Alzheimer's disease?

Abstract

Previous research suggests separate neural networks for implicit (non-declarative) and explicit (declarative) memory processes. A core cognitive impairment in mild to moderate Alzheimer's disease (AD) is a pronounced declarative memory and learning deficit with relative preservation of non-declarative memory. Cholinesterase inhibitors has been purported to enhance cognitive function, and previous clinical trials consistently showed that donepezil, a reversible inhibitor of acetylcholinesterase (AChE), led to statistically significant improvements in cognition and patient function. This prospective pilot study is a randomized, double blind, placebo-controlled clinical trial investigating 10 patients with AD. Our purpose was to examine the relationship between declarative and non-declarative capability with particular emphasis on implicit sequence learning. Patients were assessed at baseline and again at 4-weeks. After participants' baseline data were obtained, each was double-blindly randomized to one of two groups: donepezil or placebo. At baseline participants were tested with two outcome measures (Serial Reaction Time Task, Alzheimer's Disease Assessment Scale-Cognitive Subscale). Participants were given either 5 mg donepezil or an identically appearing placebo to be taken nightly for 4 weeks (28 tablets), and then retested. The donepezil group demonstrated a greater likelihood of increases in both non-declarative and declarative processes. The placebo group was mixed without clearly definable trends or patterns. When the data were examined for coincidental changes in the two outcome measures together they are suggestive of a benefit from donepezil treatment for non-declarative and declarative processes.