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Cholinergic modulation of hippocampal activity during episodic memory encoding in postmenopausal women: a pilot study

Dumas, Julie A. PhD1; McDonald, Brenna C. PsyD2; Saykin, Andrew J. PsyD2; McAllister, Thomas W. MD3; Hynes, Mary L. RN3; West, John D. MS2; Newhouse, Paul A. MD1

doi: 10.1097/gme.0b013e3181e04db9
Special Section: Menopause, Cognition and Mental Health

Objective: The cholinergic system has been shown to modulate estrogen effects on cognitive performance in postmenopausal women. In an effort to further understand cholinergic contributions to cognition after menopause, this pilot study investigated the effects of two receptor-specific anticholinergic drugs on brain activation and episodic memory encoding in postmenopausal women not taking estrogen.

Methods: Six healthy postmenopausal women took part in three drug challenges using the antimuscarinic drug scopolamine (2.5 μg/kg IV), the antinicotinic drug mecamylamine (20 mg PO), and placebo. During functional magnetic resonance imaging, participants performed a visual-verbal continuous recognition memory test that allowed for the separation of encoding and recognition processes.

Results: Functional magnetic resonance imaging results showed greater hippocampal and frontal activation and less occipital activation during encoding relative to retrieval conditions. This pattern of activation was similar under both drug challenges.

Conclusions: These results suggest that the changes in the cholinergic system may, in part, be responsible for menopause-related increases in brain activation.

Menopause and the associated decrease in circulating estradiol may affect brain cholinergic systems and associated cognitive functioning. By modeling the effects of cholinergic decline on episodic memory performance and related brain activation in postmenopausal women, increased hippocampal activation was demonstrated after cholinergic blockade, suggesting a relationship between cholinergic system activity and menopause and age-related brain changes.

From the 1Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, Burlington, VT; 2Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN; and 3Brain Imaging Laboratory, Department of Psychiatry, Dartmouth Medical School, Lebanon, NH.

Received February 5, 2010; revised and accepted March 29, 2010.

A portion of this work was previously presented as a poster at the annual meeting of the American College of Neuropsychopharmacology, Scottsdale, AZ, 2008.

Funding/support: This work was supported by National Institute on Aging (NIA) F32 AG023430 to J.D., NIA R01 AG021476 and Fletcher Allen Health Care Trustees Fund grant to P.N., NIA R01 AG19771 to A.S., and National Center for Research Resources 00109 to the University of Vermont.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Paul A. Newhouse, MD, Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect St., Burlington, VT 05401. E-mail:

©2010The North American Menopause Society