Recovery of hippocampal network connectivity correlates with cognitive improvement in mild Alzheimer's disease patients treated with donepezil assessed by resting-state fMRI

J Magn Reson Imaging. 2011 Oct;34(4):764-73. doi: 10.1002/jmri.22662. Epub 2011 Jul 18.

Abstract

Purpose: To identify the neural correlates of cognitive improvement in mild Alzheimer's disease (AD) subjects following 12 weeks of donepezil treatment.

Materials and 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.

Conclusion: R-fMRI may provide novel insights into the brain's responses to AD treatment in clinical pharmacological trials, and also may predict clinical response.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / drug therapy*
  • Case-Control Studies
  • Cognition Disorders / prevention & control
  • Donepezil
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Humans
  • Indans / therapeutic use*
  • Linear Models
  • Magnetic Resonance Imaging / methods*
  • Male
  • Nerve Net / drug effects*
  • Nerve Net / pathology
  • Neuropsychological Tests
  • Piperidines / therapeutic use*
  • Recovery of Function
  • Reference Values
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Indans
  • Piperidines
  • Donepezil