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Long-term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer’ disease

  • E. Giacobini
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 62)

Abstract

During the last decade, a systematic effort to develop a pharmacological treatment for Alzheimer disease (AD) resulted into three drugs being registered for the first time in USA and Europe. All three compounds are cholinesterase inhibitors (ChEI). The major therapeutic effect of ChEI on AD patients is to maintain cognitive function at a stable level during a 6 months to one year period of treatment as compared to placebo. Additional drug effects are slowing cognitive deterioration and improving behavioral and daily living activity. Recent studies show that in many patients the cognitive stabilization effect can be prolonged up to 24 months. This long-lasting effect suggests a mechanism of action other than symptomatic and direct cholinergic. In vitro and in vivo studies have consistently demonstrated a link between cholinergic activation and APP metabolism. Lesions of cholinergic nuclei cause a rapid increase in cortical APP and CSF. The effect of such lesions can be reversed by ChEI treatment. Reduction in cholinergic neurotransmission experimental or pathological (AD) leads to amyloidogenic metabolism and contributes to the neuropathology and cognitive dysfunction. In order to explain the long-term effect of ChEI, a mechanism based on ~amyloid metabolism, is postulated. Evidence for such an effect is available at experimental as well as at clinical level. Does cholinergic stabilization imply slowing down disability or delaying disease progression?

Keywords

Alzheimer Disease Amyloid Precursor Protein Cholinesterase Inhibitor Alzheimer Disease Patient ChEI Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • E. Giacobini
    • 1
  1. 1.Department of GeriatricsUniversity Hospitals of Geneva, University of Geneva, Medical SchoolThonexSwitzerland

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