Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease

Stefan J. Teipel, Enrica Cavedo, Michel J. Grothe, Simone Lista, Samantha Galluzzi, Olivier Colliot, Marie Chupin, Hovagim Bakardjian, Didier Dormont, Bruno Dubois, Harald Hampel

Research output: Contribution to journalArticle

Abstract

We determined the value of hippocampus (Hp) and basal forebrain (BF) volumes for predicting cognitive decline and treatment response in a double-blind, randomized, placebo-controlled phase 4 trial at 28 academic centers (France) in patients with amnestic mild cognitive impairment (MCI) receiving Donepezil 10 mg daily or placebo over 12 months, and 6 months open label follow-up. Outcome measures were the rates of global and domain specific cognitive decline as non-primary efficacy endpoint. The intention-to-treat (ITT) sample analyzed comprised 215 cases. Baseline Hp volume was a significant predictor of rates of change in global cognitive function in linear mixed effects models. This effect was independent of treatment. BF volume was not associated with rates of global or domain specific cognitive decline. Rates of delayed free recall decline were higher in MCI cases treated with donepezil compared to placebo. Only Hp, but not BF volume was a useful predictor of cognitive decline in suspected prodromal AD patients. Both Hp and BF volumes were poor predictors of treatment response, questioning previous approaches on predicting treatment response without placebo control. Trial registration clinicalTrials.gov Identifier NCT00403520.

Original languageEnglish
Pages (from-to)128-135
Number of pages8
JournalNeuropharmacology
Volume108
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • Basal forebrain
  • Biomarkers
  • Cholinergic system
  • Cholinesterase inhibitors
  • Cognitive decline
  • Hippocampus
  • MCI
  • MRI
  • Prediction
  • Prodromal Alzheimer's disease
  • Therapy

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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  • Cite this

    Teipel, S. J., Cavedo, E., Grothe, M. J., Lista, S., Galluzzi, S., Colliot, O., Chupin, M., Bakardjian, H., Dormont, D., Dubois, B., & Hampel, H. (2016). Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease. Neuropharmacology, 108, 128-135. https://doi.org/10.1016/j.neuropharm.2016.02.005