title: Recovery of hippocampal network connectivity correlates with cognitive improvement in mild Alzheimer's disease patients treated with donepezil assessed by resting-state fMRI.
abstract: OBJECTIVE
  To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment.
  
  
  METHODS
  Resting-state functional connectivity magnetic resonance imaging (R-fMRI) was used to measure the hippocampal functional connectivity (HFC) in 14 mild AD and 18 age-matched normal (CN) subjects. AD subjects were scanned at baseline and after donepezil treatment. CN subjects were scanned only at baseline as a reference to identify regions correlated or anticorrelated to the hippocampus. Before each scan, participants underwent cognitive, behavioral, and functional assessments.
  
  
  RESULTS
  After donepezil treatment, neural correlates of cognitive improvement measured by Mini-Mental State Examination scores were identified in the left parahippocampus, dorsolateral prefrontal cortex (DLPFC), and inferior frontal gyrus. Improvement in AD Assessment Scale-cognitive subscale scores correlated with the HFC changes in the left DLPFC and middle frontal gyrus. Stronger recovery in the network connectivity was associated with cognitive improvement.
  
  
  CONCLUSIONS
  R-fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response.
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
authors.forename: Chunming
authors.initials: C
authors.lastname: Xie
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Ward
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Wu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Franczak
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Jones
authors.forename: Piero G
authors.initials: PG
authors.lastname: Antuono
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Li
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000188:drug therapy*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000517:prevention & control; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000187:drug effects* / Q000473:pathology; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D020127:Recovery of Function; D012016:Reference Values; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D007189:Indans; D010880:Piperidines; D000077265:Donepezil