1. ¹Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT, USA
2. ²Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Alabama School of Medicine, Birmingham, AL, USA

Correspondence: Dr P Newhouse, Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect Street, Burlington, VT 05401, USA. Tel: +1 802 847 4560; Fax: +1 802 847 7889; E-mail: paul.newhouse@uvm.edu

Received 20 September 2005; Revised 24 December 2005; Accepted 28 December 2005; Published online 15 February 2006.

Abstract

Estrogen has been shown to interact with the cholinergic system and influence cognition in animal models. This study investigated the interaction of estrogen and cholinergic system functioning and the effects of this interaction on cognitive task performance in healthy older women. Fifteen post-menopausal women were randomly and blindly placed on 1 mg of 17- estradiol or placebo for 3 months after which they participated in five anticholinergic challenge sessions, where they were administered one of two doses of the antimuscarinic drug scopolamine (SCOP) or the antinicotinic drug mecamylamine (MECA) or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Performance in multiple domains of cognition was assessed during anticholinergic drug challenge, including attention and verbal and nonverbal learning and memory. Results showed that estrogen pretreatment attenuated the anticholinergic drug-induced impairments on tests of attention and tasks with speed components. This study is the first to demonstrate the interaction of estrogen and the cholinergic system and the effects on cognitive performance in humans. The results suggest that estrogen status may affect cholinergic system tone and may be important for cholinergic system integrity.