Cholinergic enhancement of frontal lobe activity in mild cognitive impairment

Andrew J. Saykin, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Tara L. McHugh, Alexander C. Mamourian, Robert B. Santulli

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional MRI studies have examined where their effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept®) on cognition and brain activity in patients with amnestic mild cognitive impairment (MCI), a diagnosis associated with a high risk of developing AD. Nine older adults with MCI were compared with nine healthy, demographically matched controls. At baseline, patients showed reduced activation of frontoparietal regions relative to controls during a working memory task. After stabilization on donepezil (5.7 ± 1.7 weeks at 10 mg) patients showed increased frontal activity relative to unmedicated controls, which was positively correlated with improvement in task performance (r = 0.49, P = 0.05) as well as baseline hippocampal volume (r = 0.62, P < 0.05). The patients' overall cognitive function was stable or improved throughout the study. Short-term treatment with a cholinesterase inhibitor appears to enhance the activity of frontal circuitry in patients with MCI, and this increase appears to be related to improved cognition and to baseline integrity of the hippocampus. These relationships have implications for understanding the mechanisms by which cognition-enhancing medications exert their effects on brain function and for the use of functional MRI in early detection and treatment monitoring of AD and MCI.

Original languageEnglish (US)
Pages (from-to)1574-1583
Number of pages10
JournalBrain
Volume127
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cholinesterase inhibitor
  • Functional MRI
  • Hippocampal volume
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Saykin, A. J., Wishart, H. A., Rabin, L. A., Flashman, L. A., McHugh, T. L., Mamourian, A. C., & Santulli, R. B. (2004). Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain, 127(7), 1574-1583. https://doi.org/10.1093/brain/awh177