Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?

Int J Geriatr Psychiatry. 2009 Jun;24(6):638-47. doi: 10.1002/gps.2195.

Abstract

Objective: The main objective of this study was to investigate possible predictors of response to cholinesterase inhibitor (ChEI) treatment, including pre-treatment progression rates and levels of the cerebrospinal fluid (CSF) biomarkers. A secondary objective was to evaluate whether treatment with ChEI changed progression.

Methods: Out-patient individuals (n = 191) with the clinical diagnosis of Alzheimer's disease received ChEI treatment and were part of the Swedish Alzheimer Treatment Study (SATS), a prospective, longitudinal, non-randomised study in a routine clinical setting. Patients were assessed with MMSE, ADAS-cog and a global rating (CIBIC) at baseline, 2 months and every 6 months for a total period of 3 years. The following potential predictors of treatment response were investigated: age, gender, APOE epsilon 4 carrier, education, duration of disease, cognitive level, pre-treatment progression rate (in MMSE) and the levels of the CSF biomarkers A beta 42, T-tau and P-tau.

Results: Fast pre-treatment progression rate was a predictor of treatment response even after adjusting for baseline severity, another positive predictor of response. Patients in the fastest quartile of pre-treatment progression rates were significantly more prone to be responders at 2 months (adjusted OR 6.6, p = 0.001) and 6 months (adjusted OR 10.4, p < 0.001) than those in the slowest progressing quartile. Moreover, the linearity of progression was significantly changed by ChEI treatment at 6 months compared to the pre-treatment period.

Conclusion: The rate of pre-treatment progression was the most consistent positive predictor of ChEI treatment response in the routine clinical setting. The progression rate was significantly changed by ChEI treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid
  • Cholinesterase Inhibitors / therapeutic use*
  • Disease Progression*
  • Female
  • Genotype
  • Geriatric Assessment*
  • Humans
  • Male
  • Models, Statistical
  • Peptide Fragments / cerebrospinal fluid
  • Predictive Value of Tests
  • Prospective Studies
  • Psychological Tests
  • Severity of Illness Index
  • Sweden
  • Treatment Outcome
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • Cholinesterase Inhibitors
  • Peptide Fragments
  • amyloid beta-protein (40-42)
  • tau Proteins