Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer's disease: Preliminary report

Liam Zaidel, Greg Allen, C. Munro Cullum, Richard W. Briggs, Linda S. Hynan, Myron F. Weiner, Roderick McColl, Kaundinya S. Gopinath, Elizabeth McDonald, Craig D. Rubin

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


We used functional connectivity magnetic resonance imaging (fcMRI) to investigate changes in interhemispheric brain connectivity in 11 patients with mild Alzheimer's disease (AD) following eight weeks of treatment with the cholinesterase inhibitor donepezil. We examined functional connectivity between four homologous temporal, frontal, and occipital regions. These regions were selected to represent sites of AD neuropathology, sites of donepezil-related brain activation change in prior studies, and sites that are minimally affected by the pathologic changes of AD. Based on previous findings of selective, localized frontal responses to donepezil, we predicted that frontal connectivity would be most strongly impacted by treatment. Of the areas examined, we found that treatment had a significant effect only on functional connectivity between right and left dorsolateral prefrontal cortices. Implications for understanding the impact of donepezil treatment on brain functioning and behavior in patients with AD are discussed. This preliminary report suggests that fcMRI may provide a useful index of treatment outcome in diseases affecting brain connectivity. Future research should investigate these treatment-related changes in larger samples of patients and age-matched controls.

Original languageEnglish (US)
Pages (from-to)S221-S226
JournalJournal of Alzheimer's Disease
Issue numberSUPPL. 3
StatePublished - 2012


  • Alzheimer's disease
  • donepezil
  • dorsolateral prefrontal cortex
  • functional connectivity
  • hippocampus
  • magnetic resonance imaging

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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