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

Gwenn S. Smith, Elisse Kramer, Yilong Ma, Carol R. Hermann, Vijay Dhawan, Thomas Chaly, David Eidelberg

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-401
Number of pages10
JournalBrain
Volume132
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Acetylcholine
  • Alzheimer's disease
  • Citalopram
  • Galantamine
  • Positron emission tomography (PET)
  • Serotonin

ASJC Scopus subject areas

  • Clinical Neurology

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