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

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• 作者：Bruno Dubois^a ; ^b ; ^c ; ^{bruno.dubois@psl.aphp.fr" class="auth_mail" title="E-mail the corresponding author} ; Marie Chupin^b ; Harald Hampel^a ; ^b ; ^c ; Simone Lista^a ; ^b ; Enrica Cavedo^a ; ^b ; Bernard Croisile^d ; Guy Louis Tisserand^d ; Jacques Touchon^e ; Alain Bonafe^e ; Pierre Jean Ousset^f ; Amir Ait Ameur^g ; Olivier Rouaud^h ; Fré ; deric Ricolfi^h ; Alain Vighetto^d ; Florence Pasquierⁱ ; Christine Delmaire^j ; Mathieu Ceccaldi^k ; Nadine Girard^k ; Carole Dufouil^l ; Sté ; phane Lehericy^b ; ^c ; ^m ; Isabelle Tonelliⁿ ; Franç ; oise Duveauⁿ ; Olivier Colliot^b ; Line Garnero^b ; Marie Sarazin^a ; ^b ; ^c ; Didier Dormont^b ; ^c ; ^o ; ; the &ldquo ; Hippocampus Study Group&rdquo ; O. Godefroy ; H. Deramond ; F. Etcharry Bouyx ; A. Pasco Papon ; J.F. Dartigues ; M. Allard ; O. Rouaud ; F. Ricolfi ; O. Moreaud ; A. Krainik ; F. Pasquier ; S. Bombois ; C. Delmaire ; P. Couratier ; A. Maubon ; A. Vighetto ; B. Croisile ; G. Louis-Tisserand ; M. Ceccaldi ; N. Girard ; B. Michel ; M.P. Peretti ; J. Touchon ; A. Bonafe ; A. Benetos ; G. Barroche ; S. Bracard ; M. Vercelletto ; E. Calvier Auffray ; P. Robert ; S. Chanalet ; B. Dubois ; D. Dormont ; S. Lehericy ; 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 ; P.J. Ousset ; M. Puel ; A. Ait Ameur ; H. Dumas ; K. Mondon ; J.P. Cottier
• 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
• 刊名：Alzheimer's & Dementia
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：11
• 期：9
• 页码：1041-1049
• 全文大小：791 K

文摘

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.