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

被引:105
作者
Dubois, Bruno [1 ,2 ,3 ]
Chupin, Marie [2 ]
Hampel, Harald [1 ,2 ,3 ]
Lista, Simone [1 ,2 ]
Cavedo, Enrica [1 ,2 ]
Croisile, Bernard [4 ]
Tisserand, Guy Louis [4 ]
Touchon, Jacques [5 ]
Bonafe, Alain [5 ]
Ousset, Pierre Jean [6 ]
Ameur, Amir Ait [7 ]
Rouaud, Olivier [8 ]
Ricolfi, Frederic [8 ]
Vighetto, Alain [4 ]
Pasquier, Florence [9 ]
Delmaire, Christine [10 ]
Ceccaldi, Mathieu [11 ]
Girard, Nadine [11 ]
Dufouil, Carole [12 ]
Lehericy, Stephane [2 ,13 ]
Tonelli, Isabelle [14 ]
Duveau, Francoise [14 ]
Colliot, Olivier [2 ]
Garnero, Line [2 ]
Sarazin, Marie [1 ,2 ,3 ]
Dormont, Didier [2 ,3 ,15 ]
机构
[1] Hop La Pitie Salpetriere, AP HP, Dept Neurol, Inst Memoire & Malad Alzheimer IM2A, Paris, France
[2] CNRS, UMR S975, INSERM, Inst Cerveau & Moelle Epiniere ICM, Paris, France
[3] Univ Paris 06, Sorbonne Univ, Paris, France
[4] Hop Neurol & Neurochirurg P Wertheimer, Lyon, France
[5] CHR Montpellier, F-34059 Montpellier, France
[6] Hop Casselardit, Toulouse, France
[7] Clin Pasteur, Toulouse, France
[8] Hop Gen, Dijon, France
[9] Univ Lille Nord France UDSL, CHRU, Neurol Clin, Lille, France
[10] Hop Roger Salengro, Lille, France
[11] Hop Enfants La Timone, Marseille, France
[12] Univ Bordeaux, Ctr INSERM Epidemiol & Biostat U897, Bordeaux, France
[13] Hop La Pitie Salpetriere, ICM, CENIR, Neuroimaging Unit, Paris, France
[14] Eisai SAS, Paris 2, France
[15] Hop La Pitie Salpetriere, Dept Neuroradiol, Paris, France
关键词
Randomized controlled trial; Amnestic MCI; MRI; Volumetric imaging; Donepezil; Rate of atrophy; Hippocampus; Whole brain analysis; Alzheimer's disease; Prodromal Alzheimer's disease; Mild cognitive impairment; Biomarker; Therapy; AMNESTIC SYNDROME; BRAIN LOSS; PROGRESSION; MRI; SEGMENTATION; TRAJECTORIES; VALIDATION; BIOMARKER; TRIAL;
D O I
10.1016/j.jalz.2014.10.003
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 1 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 5 92 and donepezil 5 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. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:1041 / 1049
页数:9
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