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Murray A. Raskind, MD; Elaine R. Peskind, MD; Richard C. Veith, MD; Steven C. Risse, MD; Thomas H. Lampe, MD; Soo Borson, MD; Gail Gumbrecht; Daniel M. Dorsa, PhD

Arch Gen Psychiatry. 1989;46(6):535-540.

Abstract
• To assess central nervous system cholinergic neuroendocrine regulation in Alzheimer's disease (AD), we measured plasma arginine vasopressin, β-endorphin, and epinephrine responses to a cholinergic challenge elicited by intravenous administration of the acetylcholinesterase inhibitor physostigmine (0.0125 mg/kg) in male patients with AD (n =12) and compared their responses with those of age-matched normal control subjects (n =12). Physostigmine promptly increased plasma arginine vasopressin (tenfold), β-endorphin (twofold to threefold) and epinephrine (threefold) levels in elderly control subjects. In contrast, patients with AD showed attenuated responses to physostigmine. When controls and patients with AD who experienced nausea (n = 2 and n = 6, respectively) were excluded, the arginine vasopressin, β-endorphin, and epinephrine responses of patients with AD were significantly less than those of control subjects. These data suggest that the central nervous system cholinergic deterioration of AD results in decreased responsiveness of neuroendocrine systems that are regulated by central cholinergic mechanisms.

Author Affiliations
From the Departments of Psychiatry and Behavioral Sciences (Drs Raskind, Peskind, Veith, Risse, Lampe, Borson, and Dorsa and Ms Gumbrecht), Medicine (Dr Dorsa), and Pharmacology (Dr Dorsa), University of Washington School of Medicine, Seattle; and the Seattle-American Lake Veterans Administration Geriatric Research, Education, and Clinical Center (Drs Raskind, Peskind, Veith, Risse, Lampe, Borson, and Dorsa and Ms Gumbrecht).

Footnotes
Accepted for publication Aug 5, 1988.

Reprint requests to Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, 1660 S Columbian Way, Seattle, WA 98108 (Dr Raskind).

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