Therapeutic effects of an acetylcholinesterase inhibitor (donepezil) on memory in Wernicke-Korsakoff's disease.

Wernicke-Korsakoff's disease (WKD) is cognitively an amnestic state resulting from strategic lesions in the limbic system subserving the episodic memory network and resulting from thiamine deficiency. Neurochemical deficits have been implicated in the pathophysiology of amnesia based on the pathologic observations that various brainstem and basal forebrain nuclei are also affected. Previous treatment attempts with serotoninergic, noradrenergic, and cholinergic drugs have given controversial results. The objective of this study was to assess the effects of a cholinesterase inhibitor, donepezil, on memory, attention, and executive functions in patients with nonalcoholic WKD. Seven patients who developed WKD after a hunger strike were included in this single, blind, placebo-controlled, one-way, crossover study. The patients were administered donepezil during the first 30 days, and were administered placebo during the following 30 days. Neuropsychological tests to evaluate verbal and visual memory, and attention and executive function were performed on days 0, 31, and 61. All patients completed both phases of the study. There were no statistically significant differences between the three evaluations, except for a difference between active treatment and the placebo phase during recall of the Rey-Osterrieth complex figure, which was in favor of the placebo phase. There were no significant changes in favor of the active treatment. Cholinergic treatment with the cholinesterase inhibitor donepezil does not seem to provide marked beneficial effects in patients with WKD in this small, descriptive study. This may be because pathways mediating channel and state-dependent functions are impaired in this disease, and enhancement of state-dependent cholinergic transmission may not be sufficient. Subtle benefits, however, cannot be excluded because of the small sample size and the relatively short duration of the treatment.