CHOLINERGIC TREATMENT OF AN AMNESTIC MAN WITH A BASAL FOREBRAIN LESION - THEORETICAL IMPLICATIONS

Cholinergic deficient states, such as in Alzheimer's disease, are asso ciated with amnesia. Therapeutic trials with cholinergic augmentation in Alzheimer's disease have had only equivocal results, but mechanisms other than cholinergic deficiency may contribute to the memory defici t. Normally the diagonal band of Broca provides much of the hippocampa l cholinergic input. To learn if amnesia secondary to cholinergic defi ciency can be ameliorated by cholinergic augmentation, we treated an a mnestic man who had a lesion located primarily in the right diagonal b and of Broca with physostigmine and lecithin. During the initial best- dose-finding phase, he demonstrated an inverted U-shaped curve for imm ediate recall of word lists, with peak performances at 3.0 and 3.5 mg of physostigmine. Single photon emission tomography showed decreased b lood flow in the medial temporal region ipsilateral to the lesion at b aseline, with a reversal of the asymmetry on 3.5 mg of physostigmine. A follow-up double-blind, placebo-controlled study on 3.5 mg of physos tigmine, however, failed to demonstrate that cholinergic treatment imp roved memory.