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Cholinergic enhancement of frontal lobe activity in mild cognitive impairment

Andrew J Saykin1, Heather A Wishart, Laura A Rabin

  • 1Brain Imaging Laboratory, Department of Psychiatry, Dartmouth Medical School, Lebanon, NH 03756, USA. Andrew.J.Saykin@dartmouth.edu

Brain : a Journal of Neurology
|May 14, 2004
PubMed

Insights

Cholinesterase inhibitors like donepezil improved cognitive function and frontal brain activity in individuals with mild cognitive impairment (MCI). This enhancement correlated with better task performance and hippocampal volume, suggesting therapeutic potential for Alzheimer's disease (AD).

Area of Science:

  • Neuroscience
  • Cognitive Science
  • Pharmacology

Background:

  • Cholinesterase inhibitors improve cognition in Alzheimer's disease (AD) but their brain activity effects are unexamined by functional MRI.
  • Mild cognitive impairment (MCI) is a high-risk diagnosis for AD.
  • Frontoparietal dysfunction is observed in MCI during cognitive tasks.

Purpose of the Study:

  • To investigate the effects of donepezil hydrochloride on cognition and brain activity in patients with amnestic MCI.
  • To identify the neural correlates of cognitive improvement induced by cholinesterase inhibitors.

Main Methods:

  • A controlled functional MRI study comparing nine MCI patients with nine healthy controls.
  • Assessment of working memory task performance and brain activation before and after donepezil treatment in MCI patients.
  • Correlation analysis between cognitive improvement, brain activity changes, and baseline hippocampal volume.

Main Results:

  • MCI patients showed reduced frontoparietal activation at baseline compared to controls.
  • Donepezil treatment increased frontal activity in MCI patients, correlating positively with improved task performance (r=0.49, P=0.05).
  • Increased frontal activity also correlated with baseline hippocampal volume (r=0.62, P<0.05); cognitive function remained stable or improved.

Conclusions:

  • Short-term donepezil treatment enhances frontal brain activity in MCI patients.
  • This enhancement is linked to improved cognition and baseline hippocampal integrity.
  • Findings support the use of functional MRI for monitoring MCI/AD treatment and understanding medication mechanisms.

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