Improved verbal learning after outpatient oral physostigmine therapy in patients with dementia of the Alzheimer type

Abstract

Background: Previous investigators have reported improvements in verbal learning in outpatients suffering from dementia of the Alzheimer type (DAT) when they were treated daily with oral physostigmine for periods of days to months. Questions remain, however, regarding both the specificity of the induced cognitive changes and the time course of the biological activity of the drug when physostigmine was used to treat DAT patients. We examined both of these parameters in an outpatient, double-blind, placebo-controlled study that examined the effect of physostigmine on memory and other cognitive functions.

Method: Eight DAT patients were treated for 3 weeks with oral physostigmine administered four times daily in a double-blind, crossover, placebo-controlled study. An auditory verbal learning test (AVLT) was administered to assess verbal learning. Digit span, word fluency, and frequency of intrusions served as controls for nonspecific changes in attention and verbal responsiveness.

Results: AVLT scores improved after drug administration compared with scores for baseline and placebo performances (p = .04). Other measures were unchanged. Improvement was unrelated to the time interval between memory testing and last ingested dose.

Conclusions: These results indicate a longer period of biological activity for physostigmine than previously considered and extend previous reports of improved verbal learning after oral physostigmine treatment to a more convenient dosing schedule. These results suggest further that the improvements induced by physostigmine result specifically from enhancement of long-term memory processes.