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A Dose-Response Study

Trey Sunderland; Pierre N. Tariot, MD; Robert M. Cohen, MD, PhD; Herbert Weingartner, PhD; Edward A. Mueller III, MD; Dennis L. Murphy, MD

Arch Gen Psychiatry. 1987;44(5):418-426.

Abstract
• We compared the cognitive and behavioral responses to three intravenous doses of scopolamine (0.1,0.25, and 0.5 mg) and placebo of ten patients with dementia of the Alzheimer type (DAT) and ten age- and sex-matched elderly control subjects. The patients with DAT showed significant behavioral and cognitive but not physiologic changes at a lower scopolamine dose (0.25 mg) than did the normal elderly controls. Cognitive tests of new learning and semantic knowledge revealed significant impairments at the 0.25-mg scopolamine dose in the patients with DAT, while the responses of the control population were essentially unchanged. Behaviorally, mild euphoria, motor incoordination, and hostility occurred in the patients with DAT but not the controls at the 0.25-mg dose. These differences were unrelated to peripheral physiologic changes produced by the different scopolamine doses. These results indicate that central nervous system functions such as cognition and certain elements of behavior are more sensitive to temporary cholinergic blockade In patients with DAT than in normal age-matched controls. We review implications concerning the status of central cholinergic function in patients with DAT in light of neuropathologically demonstrated cholinergic system lesions in DAT.

Author Affiliations
From the Section on Clinical Neuropharmacology, Laboratory of Clinical Science (Drs Sunderland, Tariot, Mueller, and Murphy), and the Section on Clinical Brain Imaging, Laboratory of Cerebral Metabolism (Dr Cohen), National Institute of Mental Health, Bethesda, Md; and the Laboratory of Psychology and Psychopathology, National Institute of Drug Abuse, Bethesda, Md (Dr Weingartner).

Footnotes
Accepted for publication July 2, 1986.

Presented in part at the Annual Meeting of the American College of Neuropsychology, San Juan, Puerto Rico, Dec 14, 1984.

Reprint requests to Bldg 10, Room 3D41, Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892 (Dr Sunderland).

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