Neuroendocrine responses to physostigmine in Alzheimer's disease

To assess central nervous system cholinergic neuroendocrine regulation in Alzheimer's disease (AD), we measured plasma arginine vasopressin, beta-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), beta-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, beta-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.