title: Donepezil Enhances Frontal Functional Connectivity in Alzheimer's Disease: A Pilot Study.
abstract: BACKGROUND
  We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks.
  
  
  METHODS
  18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil. We tested if changes in cognitive performance after treatment correlated with changes in FC in resting-state networks known to be altered in AD.
  
  
  RESULTS
  We found increases in FC in the orbitofrontal network that correlated with cognitive improvement after treatment. The increased FC was greatest in patients who responded most to treatment.
  
  
  CONCLUSIONS
  This 'proof of concept' study suggests that changes in network-specific FC might be a biomarker of pharmacological intervention efficacy in AD.
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Griffanti
authors.affiliation: Oxford Project to Investigate Memory and Ageing, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK, Oxford, UK.
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Voets
authors.affiliation: Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Guendalina
authors.initials: G
authors.lastname: Bonifacio
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK; Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Mackay
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkinson
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK; Oxford Project to Investigate Memory and Ageing, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK, Oxford, UK; Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Università di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zamboni
keywords: Alzheimer's disease; Cholinesterase inhibitors; Donepezil; Functional connectivity; Functional magnetic resonance imaging; Resting-state networks