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From the Departments of Neurological Surgery (Dr. Penn), Psychology and Social Sciences (Drs. Martin and Wilson), Neurological Sciences (Dr. Fox), and Surgical Nursing (Ms. Savoy), and Rush Alzheimer's Disease Center (Drs. Wilson and Fox), Rush-Presbyterian-St Luke's Medical Center, Chicago, IL.
Ten patients with biopsy-proven Alzheimer's disease (AD) received low-dose (0. 35 mg/d) intraventricular bethanechol, a muscarinic agonist, and saline placebo in a 24-week double-blind crossover design. Eight of these ten patients later participated in an open escalating-dose (to 1.75 mg/d) trial of bethanechol. Patients' drug responses were assessed by neuropsychological examination and informant measures of activities of daily living, mood disturbance, and abnormal behavior. Bethanechol appears to have a narrow therapeutic window for positive effects; low doses did not reliably alter patient functioning, moderately increased doses appeared to have a palliative effect on patient mood and behavior, and the highest dose was detrimental to patient functioning. Bethanechol does not appear to ameliorate the dementia of AD, but may exert a mildly positive effect on patient behavior and mood.
Address correspondence and reprint requests to Dr. Penn, Department of Neurological Surgery, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612.
Supported by a grant from Intermedics-Infusaid to Drs. Penn and Fox.
Received January 27, 1987. Accepted for publication in final form May 4, 1987.
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