title: Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo.
authors.affiliation: Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France. Electronic address: bruno.dubois@psl.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.affiliation: INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Chupin
authors.affiliation: Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.affiliation: Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Lista
authors.affiliation: Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
authors.forename: Enrica
authors.initials: E
authors.lastname: Cavedo
authors.affiliation: Hôpital Neurologique Pierre Wertheimer, Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Croisile
authors.affiliation: Hôpital Neurologique Pierre Wertheimer, Lyon, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Louis Tisserand
authors.affiliation: CHRU, Gui de Chauliac, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.affiliation: CHRU, Gui de Chauliac, Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bonafe
authors.affiliation: Hôpital Casselardit, Toulouse, France.
authors.forename: Pierre Jean
authors.initials: PJ
authors.lastname: Ousset
authors.affiliation: Clinique Pasteur, Toulouse, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Ait Ameur
authors.affiliation: Hôpital Général, Dijon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rouaud
authors.affiliation: Hôpital Général, Dijon, France.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Ricolfi
authors.affiliation: Hôpital Neurologique Pierre Wertheimer, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Vighetto
authors.affiliation: CHRU, Clinique de Neurologie, Univ Lille Nord de France UDSL, EA1046, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Hôpital Roger Salengro, Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Delmaire
authors.affiliation: Hôpital de la Timone, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Ceccaldi
authors.affiliation: Hôpital de la Timone, Marseille, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Girard
authors.affiliation: Centre INSERM U897-Epidemiologie & Biostatistique, Université de Bordeaux, Bordeaux, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Dufouil
authors.affiliation: INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France; CENIR, Neuroimaging Unit, ICM, Hôpital de la Salpêtrière, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lehericy
authors.affiliation: Eisai SAS, La Defense 2 Cedex, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tonelli
authors.affiliation: Eisai SAS, La Defense 2 Cedex, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Duveau
authors.affiliation: INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Colliot
authors.affiliation: INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
authors.forename: Line
authors.initials: L
authors.lastname: Garnero
authors.affiliation: Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Sarazin
authors.affiliation: INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, Paris, France; Neuroradiology Department, Hôpital de la Salpêtrière, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Dormont
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D001284:Atrophy / Q000188:drug therapy; D018450:Disease Progression; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D005602:France; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D009929:Organ Size; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D062706:Prodromal Symptoms; D016896:Treatment Outcome
chemical_list: D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D000077265:Donepezil
keywords: Alzheimer's disease; Amnestic MCI; Biomarker; Donepezil; Hippocampus; MRI; Mild cognitive impairment; Prodromal Alzheimer's disease; Randomized controlled trial; Rate of atrophy; Therapy; Volumetric imaging; Whole brain analysis