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Brain Advance Access published online on January 19, 2009
Brain, doi:10.1093/brain/awn326
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© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease

Gwenn S. Smith1,2, Elisse Kramer3, Yilong Ma2, Carol R. Hermann3, Vijay Dhawan2, Thomas Chaly2 and David Eidelberg2

1 Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, New York 11004, USA 2 Centre for Neurosciences, The Feinstein Institute for Medical Research, North Shore – Long Island Jewish Health System, Manhasset, New York 11030, USA 3 Department of Geriatric Psychiatry, The Zucker Hillside Hospital, Glen Oaks, New York 11004, USA

Correspondence to: Gwenn Smith, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Centre, 5300 Alpha Commons Drive, Fourth Floor, Baltimore, MD 21224, USA E-mail: gsmith95{at}jhmi.edu

Pre-clinical and human neuropharmacological evidence suggests a role of cholinergic modulation of monoamines as a pathophysiological and therapeutic mechanism in Alzheimer's disease. The present study measured the effects of treatment with the cholinesterase inhibitor and nicotinic receptor modulator, galantamine, on the cerebral metabolic response to the selective serotonin reuptake inhibitor, citalopram. Seven probable Alzheimer's disease patients and seven demographically comparable controls underwent two positron emission tomography (PET) glucose metabolism scans, after administration of a saline placebo infusion (Day 1) and after citalopram (40 mg, IV, Day 2). The scan protocol was repeated in the Alzheimer's disease patients 2 months after titration to a 24 mg galantamine dose. At baseline, cerebral glucose metabolism was reduced in Alzheimer's disease patients relative to controls in right middle temporal, left posterior cingulate and parietal cortices (precuneus and inferior parietal lobule), as expected. Both groups demonstrated acute decreases in cerebral glucose metabolism after citalopram to a greater extent in the Alzheimer's disease patients. In the patients, relative to the controls, citalopram decreased glucose metabolism to a greater extent in middle frontal gyrus (bilaterally), left middle temporal gyrus and right posterior cingulate prior to treatment. Galantamine treatment alone increased metabolism in the right precuneus, right inferior parietal lobule and right middle occipital gyrus. In contrast, during galantamine treatment, citalopram increased metabolism in the right middle frontal gyrus, right post-central gyrus, right superior and middle temporal gyrus and right cerebellum. The combined cerebral metabolic effects of galantamine and citalopram suggest, consistent with preclinical data, a synergistic interaction of cholinergic and serotonergic systems.

Key Words: Alzheimer's disease; positron emission tomography (PET); acetylcholine; serotonin; citalopram; galantamine

Abbreviations: ADAS-COG, Alzheimer's disease Assessment Scale score; MCI, mild cognitive impairment; MMSE, mini mental status examination; NPI, Neuropsychiatric Inventory; PET, positron emission tomography

Received May 13, 2008. Revised October 23, 2008. Accepted November 6, 2008.


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