Peripheral Vascular Responses to Acetylcholine as a Predictive Tool for Response to Cholinesterase Inhibitors in Alzheimer's Disease

Peter Connelly, Fiona Adams, Ziad I. Tayar, Faisel Khan (Lead / Corresponding author)

Research output: Contribution to journalArticle

2 Citations (Scopus)
109 Downloads (Pure)

Abstract

Background: Cholinesterase inhibitors remain the first line therapy for people with mild to moderate Alzheimer's disease (AD). Response is modest and difficult to predict from pre-treatment characteristics. We hypothesise that skin vascular response to iontophoresis of acetylcholine, which is partly determined by the level of cholinesterase activity, may be a pre-treatment measure that could predict response to therapy.
Methods: Twenty-four people with probable AD underwent iontophoresis of acetylcholine to the volar surface of the forearm skin prior to treatment with a cholinesterase inhibitor. The peak skin vascular response and the resolution to baseline levels were measured using laser Doppler perfusion imaging. Response to treatment was assessed after 6 months using criteria from the National Institute for Health and Care Excellence (NICE) and iontophoresis with acetylcholine was repeated. Blindness between clinical and laboratory assessments was maintained.
Results: Fourteen out of twenty-four people responded to treatment using NICE criteria. By comparison to non-responders, responders to treatment had a faster resolution to baseline from acetylcholine-induced vasodilation prior to treatment, which slowed with treatment. In this pilot study there was a high level of accuracy in the classification of response using this variable. No baseline cognitive or functional measures discriminated end-point responders from non-responders.
Conclusion: Cholinesterase inhibitors are well tolerated but the number of people with adverse effects would be reduced if it was possible to predict response. The role of vasodilator response to acetylcholine and recovery as a potential biomarker for efficacy of treatment should now be evaluated and may possibly be of relevance in stratifying samples for interventional studies in AD and other forms of dementia. We feel that a more definitive study is now justified.
Original languageEnglish
Article number88
Pages (from-to)1-7
Number of pages7
JournalBMC Neurology
Volume19
Issue number1
DOIs
Publication statusPublished - 3 May 2019

Keywords

  • Cholinesterase
  • Acetylcholine
  • blood flow
  • Doppler
  • vascular response
  • Prediction
  • Laser Doppler, vascular response
  • Acetylcholine, blood flow
  • Cholinesterase Inhibitors/therapeutic use
  • Humans
  • Acetylcholine/pharmacology
  • Male
  • Vasodilator Agents/pharmacology
  • Iontophoresis
  • Pilot Projects
  • Alzheimer Disease/classification
  • Aged, 80 and over
  • Female
  • Aged
  • Skin/drug effects

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