Eight patients with early Alzheimer disease were treated with gradually increasing multiple daily doses of oral physostigmine and supplemental lecithin. Six individuals showed improvement in total recall and retrieval from long-term storage (LTR), with a decrease in intrusions (a measure of inaccurate recall). The optimal individual dose was either 2.0 or 2.5 mg of physostigmine for each responding patient. Results of this open trial were subsequently replicated during a double-blind crossover trial comparing physostigmine treatment to placebo. All six patients again demonstrated improvement in total recall and LTR, with a decrease in intrusions. The decrease in intrusions was strongly correlated with increasing inhibition of cholinesterase activity in cerebrospinal fluid, suggesting that the degree of improvement in the patient's memory was related to the amount of physostigmine that reached the brain. Other neurotransmitters and metabolites in cerebrospinal fluid were unaffected by the physostigmine therapy, suggesting a specific effect of physostigmine on the cholinergic system. The results suggest that small oral doses of physostigmine combined with lecithin ingestion have therapeutic benefit for some patients with Alzheimer disease.

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