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Minimal short-term benefits with oral physostigmine have been reported in Alzheimer's disease.We examined long-term oral physostigmine therapy in 14 patients with probable Alzheimer's disease in an extended double-blind crossover trial in which they received physostigmine for five intervals of 4 to 6 weeks in length and placebo for one interval determined at random. At each interval a Selective Reminding Test was administered and three indexes were examined:total recall,long-term recall,and intrusions.As a group,patients'memory test scores were significantly better during the drug period.Two patients who previously had performed worse on drug than on placebo in a short-term trial continued to do so.Nine of the remaining 12 patients performed better on two or more measures on physostigmine compared with placebo.In some cases scores improved up to 50%over placebo values.This improvement was not predicted by response to medication in the earlier short-term trial.Seven patients completed an additional six- interval crossover trial.All but one continued to have improved performance with oral physostigmine and,in grouped data,memory measures remained significantly improved.These results suggest that long-term administration of physostigmine in Alzheimer's disease may be more effective than short-term.This benefit can be sustained for up to a year in some patients. |
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