Arecoline, a cholinergic agonist, improves memory in patients with Alzheimer's disease when given by continuous intravenous infusion. The degree of improvement follows an inverted U-shaped relation to dose, and is maximal at a dose at least ten-fold below that producing toxicity. A plasma concentration was identified that achieves maximal cognitive improvement in responding patients. Physostigmine, a cholinesterase inhibitor, given by continuous intravenous infusion improved cognition in some subjects with Alzheimer's disease, but was associated with many adverse effects. Administration of haloperidol, a dopamine antagonist, produced greater cognitive and motor effects in young than in aged healthy men, suggesting that responsivity of the brain dopamine system is reduced with age in humans.
