Oral physostigmine treatment of patients with Alzheimer's disease

Twelve patients with Alzheimer's disease received 0.0, 0.5, 1.0, 1.5, and 2.0 mg of oral physostigmine every 2 hours for 3-5 days; symptoms after each dose were assessed with the Alzheimer's Disease Assessment Scale. Placebo and the dose associated with the least severe symptoms were then readministered for 3-5 days each. Of the 10 patients who completed the study, three showed clinically significant improvement on the highest physostigmine dose in both phases, four more were marginally improved in both phases, and three had inconsistent responses to physostigmine. Cortisol measures obtained during a sleep study suggest that patients whose symptoms improved on physostigmine were those in whom oral physostigmine enhanced central cholinergic activity.