Relevance of Donepezil in Enhancing Learning and Memory in Special Populations: A Review of the Literature

Abstract

This review discusses the laboratory and clinical research supporting the rationale for the efficacy of donepezil (Aricept USA) in enhancing cognition in autism, Alzheimer disease, Down syndrome, traumatic brain injury, Attention Deficit Hyperactivity Disorder (ADHD), and schizophrenia. While preliminary animal models have shown effective, human studies exclusive of Alzheimer disease are sparse. Although attention and memory are unlikely a sole operation of the cholinergic system, evidence indicates a promising direction for further examination of this hypothesis in autism. Studies that examine changes in operationally defined behaviors and reliable and valid measure of changes in attention and memory are needed.

Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

“…Systemic administration of the drug in the BTBR mouse model of autism improved cognitive flexibility, comparable to the results obtained in spatial reversal learning tests after administration of Donepezil in doses similar to the current study (Yoo et al, 2007). In addition, our results in the social novelty test of untreated BTBR mice agrees with a previous report (Moy et al, 2007), in which these mice spent significantly more time in the chamber containing the novel stranger, but not in physical contact with it.…”

“…Similar effects were achieved by direct microinjection into the dorsomedial striatum but not into the ventomedial-striatum. The effect of the AChEI Donepezil on cognitive functions was previously examined extensively on neurotypical mice and rats or animal models of Alzheimer disease (Yoo et al, 2007), but, to our knowledge, never on ASD animal models. For example, the positive behavioral effect of the drug was shown with respect to attention, learning, and memory (reviewed in (Yoo et al, 2007)).…”

“…The effect of the AChEI Donepezil on cognitive functions was previously examined extensively on neurotypical mice and rats or animal models of Alzheimer disease (Yoo et al, 2007), but, to our knowledge, never on ASD animal models. For example, the positive behavioral effect of the drug was shown with respect to attention, learning, and memory (reviewed in (Yoo et al, 2007)). In addition, Donepezil treatment was demonstrated to increase spontaneous alternations (Spowart-Manning and van der Staay, 2004), improve reversal learning in spatial-tasks (Dong et al, 2005), and relieve social memory deficiency (Riedel et al, 2009).…”

“…A more common and validated method to increase ACh availability in the brain is inhibiting acetylcholinesterase (AChE), and numerous studies revealed improvement in the cognitive abilities of attention, memory, and reversal learning following treatment with AChE inhibitors (acetylcholinesterase inhibitor, AChEI, eg, Donepezil, reviewed in (Yoo et al, 2007)). Most studies focused on the impact on Alzheimer's disease, yet a handful of studies examined the effect of the CNS-specific AChEI Donepezil on ASD symptoms.…”

Safety and Efficacy of Donepezil in Children and Adolescents with Autism: Neuropsychological Measures

“…Chez et al (2003) also documented gains on measures of expressive and receptive language as well as core ASD features (using the Childhood Autism Rating Scale) in a double-blind study of 43 children who were placed on a 2.5 mg/day dose of donepezil. However, the results were equivocal, as betweengroup statistical analyses were not conducted and the placebo group evidenced greater improvement on some measures than those on active medication (Yoo et al 2007). Niederhofer et al (2002) reported the results of a double-blind, placebo-controlled crossover trial of galantamine with 20 children with ASD.…”