Preliminary report: intracranial cholinergic drug infusion in patients with Alzheimer's disease

After toxicity studies in dogs, a preliminary feasibility trial of the continuous intracranial infusion of a muscarinic agonist was begun in four patients with biopsy-documented Alzheimer's disease. During the last 8 months, a totally implantable infusion system has been used to deliver bethanechol chloride into the cerebrospinal fluid of these patients at doses of 0.05 to 0.7 mg/day. Complications have been few and resolved spontaneously or were easily reversible. The subjective response to this treatment has been encouraging, with reports of improved cognitive and social function during drug infusion and a return to base line function with single-blind saline placebo infusions. Obviously, further evaluation will be necessary to demonstrate the efficacy of this treatment, and a double-blind placebo-controlled crossover trial is now being done. However, we think the preliminary results are encouraging and warrant the consideration of this approach as a potential treatment in patients with Alzheimer's disease.