title: Donepezil effects on hippocampal and prefrontal functional connectivity in Alzheimer's disease: preliminary report.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Liam
authors.initials: L
authors.lastname: Zaidel
authors.forename: Greg
authors.initials: G
authors.lastname: Allen
authors.forename: C Munro
authors.initials: CM
authors.lastname: Cullum
authors.forename: Richard W
authors.initials: RW
authors.lastname: Briggs
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.forename: Myron F
authors.initials: MF
authors.lastname: Weiner
authors.forename: Roderick
authors.initials: R
authors.lastname: McColl
authors.forename: Kaundinya S
authors.initials: KS
authors.lastname: Gopinath
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McDonald
authors.forename: Craig D
authors.initials: CD
authors.lastname: Rubin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077265:Donepezil; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil