Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease

Acta Neurol Scand. 2011 Aug;124(2):122-9. doi: 10.1111/j.1600-0404.2010.01435.x. Epub 2010 Sep 29.

Abstract

Objectives: To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs).

Materials and methods: Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1- year treatment.

Results: Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment.

Conclusions: AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acetylcholinesterase / blood
  • Acetylcholinesterase / cerebrospinal fluid*
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Butyrylcholinesterase / blood
  • Butyrylcholinesterase / cerebrospinal fluid*
  • Cholinesterase Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Statistics, Nonparametric
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Acetylcholinesterase
  • Butyrylcholinesterase