Effects of long-term continuous infusion of the muscarinic cholinergic agonist arecoline on verbal memory in dementia of the Alzheimer type

Abstract

Alzheimer's disease (AD) is accompanied by depletion of cholinergic markers in the central nervous system. In an attempt to improve cognitive function in AD, arecoline (a muscarinic cholinergic receptor agonist) was given to patients with probable or possible AD in a two-phase design, and verbal memory function was examined. First, escalating doses of arecoline, range .5-40 mg/day, were administered by continuous intravenous infusion over a 2-week period. Based on neuropsychological test performance, an optimal dose of arecoline was identified, and this dose then was infused continuously for 5 days in a double-blind, placebo-controlled, counter-balanced trial. Long-term recall on a selective reminding task was significantly improved (from 11.8 to 20.1 words, p less than .05) during dose finding by arecoline at 4 mg/day. Two of eight patients were nonresponders; that is, they showed no improvement at any dose during the dose-finding study. Responders demonstrated significant improvement on total recall (p less than .05) during the double-blind study. These results indicate that some patients demonstrate reliable improvements of verbal memory during arecoline treatment.