Oral physostigmine and lecithin improve memory in Alzheimer disease

Abstract

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.

A Pilot Study of Clonidine Plus Physostigmine in Alzheimer's Disease

“…A modest beneficial effect of oral physostigmine on cognitive function in AD has been shown by several pre vious studies [2,17,18]. The small number of patients in this pilot study may explain the lack of group benefit with physostigmine alone.…”

“…The small number of patients in this pilot study may explain the lack of group benefit with physostigmine alone. Oral administration of physostig mine yields variable blood levels [19] and cerebrospinal fluid cholinesterase inhibition [17], so that a heteroge neous clinical response may be expected. Two patients in this study did show an improvement in ADAS score of at least 4 points with physostigmine.…”

Study of the interaction of Huperzia saururus Lycopodium alkaloids with the acetylcholinesterase enzyme

“…[19] Among these compounds are found physostigmine (1), [20][21][22] Huperzine A (2), [23,24] and galanthamine (3). [25,26] Other AChEIs of relevance, but obtained by synthesis, are Tacrine (4), [27] donepezil (5) [28,29] and rivastigmine (6), [30] the latter being a semi-synthetic derivative of 1.…”

Galantamine: Additional Benefits to Patients with Alzheimer’s Disease

“…There is already some evidence that combining two cholinergic mechanisms may produce greater efficacy in the treatment of AD. For example, the addition of lecithin to physostigmine, an AChE inhibitor, may improve memory to a greater extent than physostigmine alone [20].…”