Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease

Bruno Dubois, Marie Chupin, Harald Hampel, Simone Lista, Enrica Cavedo, Bernard Croisile, Guy Louis Tisserand, Jacques Touchon, Alain Bonafe, Pierre Jean Ousset, Amir Ait Ameur, Olivier Rouaud, Fréderic Ricolfi, Alain Vighetto, Florence Pasquier, Christine Delmaire, Mathieu Ceccaldi, Nadine Girard, Carole Dufouil, Stéphane LehericyIsabelle Tonelli, Françoise Duveau, Olivier Colliot, Line Garnero, Marie Sarazin, Didier Dormont, H. Deramond, F. Etcharry Bouyx, A. Pasco Papon, O. Moreaud, A. Krainik, S. Bombois, P. Couratier, A. Maubon, B. Croisile, G. Louis-Tisserand, B. Michel, M. P. Peretti, A. Benetos, G. Barroche, S. Bracard, M. Vercelletto, E. Calvier Auffray, P. Robert, S. Chanalet, J. Hugon, M. P. Pancrazi, D. Reizine, R. Gil, P. Vandermarcq, J. L. Novella, L. Pierot, S. Belliard, M. Carsin, O. Martinaud, E. Gerardin, B. Laurent, F. G. Barral, F. Sellal, M. Puel, H. Dumas, K. Mondon, J. P. Cottier

Research output: Contribution to journalArticlepeer-review


Introduction The purpose of this study was to study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). Methods A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method. Results Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = -1.89%) compared with the placebo group (APC = -3.47%), P <.001. There was no significant difference in neuropsychological performance between treatment groups. Discussion A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo.

Original languageEnglish
Article number1924
Pages (from-to)1041-1049
Number of pages9
JournalAlzheimer's and Dementia
Issue number9
Publication statusPublished - Sep 1 2015


  • Alzheimer's disease
  • Amnestic MCI
  • Biomarker
  • Donepezil
  • Hippocampus
  • Mild cognitive impairment
  • MRI
  • Prodromal Alzheimer's disease
  • Randomized controlled trial
  • Rate of atrophy
  • Therapy
  • Volumetric imaging
  • Whole brain analysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy

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