Using Biomarkers to Predict Memantine Effects in Alzheimer's Disease: A Proposal and Proof-Of-Concept Demonstration

J Alzheimers Dis. 2021;84(4):1431-1438. doi: 10.3233/JAD-215029.

Abstract

Memantine's benefits in Alzheimer's disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual's clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid). Study participation was well tolerated. Subgroups based on memantine sensitivity on specific laboratory measures differed in their clinical response to memantine, some by large effect sizes. It appears feasible to use biomarkers to predict clinical sensitivity to memantine.

Keywords: Alzheimer’s disease; event-related potentials; memantine; neurocognition; prepulse inhibition.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alzheimer Disease / drug therapy*
  • Biomarkers*
  • Cognition / drug effects*
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / administration & dosage*
  • Female
  • Humans
  • Male
  • Memantine / administration & dosage*
  • Neuropsychological Tests

Substances

  • Biomarkers
  • Excitatory Amino Acid Antagonists
  • Memantine