Effects of cholinesterase inhibitor on brain activation in Alzheimer's patients measured with functional near-infrared spectroscopy

Psychopharmacology (Berl). 2015 Dec;232(23):4383-91. doi: 10.1007/s00213-015-4066-z. Epub 2015 Sep 11.

Abstract

Rationale: Neurobiological effects of neuropsychiatric medication can contribute to the understanding of mechanisms of action and to the evaluation of target medication effects. Cholinesterase inhibitors (ChEI) have been used in patients with Alzheimer's disease (AD) for years with only small knowledge about the underlying neurobiological effects. The measurement of brain activation links neurobiological and functional aspects but is challenging in the group of demented patients; here, an alternative method, functional near-infrared spectroscopy (fNIRS), is introduced to measure those medication effects.

Objectives: The current study investigated the influence of ChEI on cortical activation of patients with AD measured using fNIRS during a verbal fluency task (VFT).

Methods: In this study, 24 probable AD patients were investigated three times using fNIRS: before medication with rivastigmine was given (t0), when the medication was at the target dose after 4 weeks (t1), and after the target dose was kept constant for a further 8 weeks (t2).

Results: The results show a concentration increase of oxygenated hemoglobin as measured with fNIRS from t0 to t2 in speech relevant areas and a general decrease in prefrontal areas. Behaviorally, an improvement was found for the VFT used to measure cortical activation during fNIRS. In the neuropsychological test battery, no significant changes were found, yet high effect sizes for the mini mental status examination, immediate and delayed word list recall were found.

Conclusions: The results indicate a positive effect of ChEI on cognitive function. The underlying cortical changes can be imaged using fNIRS.

Keywords: Alzheimer’s dementia; Cholinesterase inhibitors; Functional near-infrared spectroscopy; Medication against dementia; Rivastigmine patch.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / psychology
  • Brain / drug effects
  • Brain / metabolism*
  • Cholinesterase Inhibitors / administration & dosage*
  • Cognition / drug effects
  • Cognition / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Psychomotor Performance / drug effects*
  • Psychomotor Performance / physiology
  • Rivastigmine / administration & dosage
  • Spectroscopy, Near-Infrared / methods*
  • Speech / drug effects
  • Speech / physiology
  • Treatment Outcome

Substances

  • Cholinesterase Inhibitors
  • Rivastigmine