一项关于疑似前驱期阿尔茨海默病的临床试验中认知衰退和治疗反应的预测因素

Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease.

作者信息

Teipel Stefan J, Cavedo Enrica, Grothe Michel J, Lista Simone, Galluzzi Samantha, Colliot Olivier, Chupin Marie, Bakardjian Hovagim, Dormont Didier, Dubois Bruno, Hampel Harald

机构信息

German Center for Neurodegenerative Diseases (DZNE) - Rostock/Greifswald, Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.

Institut de la Memoire et de la Maladie d'Alzheimer (IM2A), Departement de Neurologie, Hôpital de la Pitie-Salpêtriere, AP-HP, Paris, France; INSERM U1127, Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France; Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6, Paris, France; CATI Multicenter Neuroimaging Platform, France; IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Italy.

出版信息

Neuropharmacology. 2016 Sep;108:128-35. doi: 10.1016/j.neuropharm.2016.02.005. Epub 2016 Feb 10.

DOI:10.1016/j.neuropharm.2016.02.005

PMID:26876309

Abstract

UNLABELLED

We determined the value of hippocampus (Hp) and basal forebrain (BF) volumes for predicting cognitive decline and treatment response in a double-blind, randomized, placebo-controlled phase 4 trial at 28 academic centers (France) in patients with amnestic mild cognitive impairment (MCI) receiving Donepezil 10 mg daily or placebo over 12 months, and 6 months open label follow-up. Outcome measures were the rates of global and domain specific cognitive decline as non-primary efficacy endpoint. The intention-to-treat (ITT) sample analyzed comprised 215 cases. Baseline Hp volume was a significant predictor of rates of change in global cognitive function in linear mixed effects models. This effect was independent of treatment. BF volume was not associated with rates of global or domain specific cognitive decline. Rates of delayed free recall decline were higher in MCI cases treated with donepezil compared to placebo. Only Hp, but not BF volume was a useful predictor of cognitive decline in suspected prodromal AD patients. Both Hp and BF volumes were poor predictors of treatment response, questioning previous approaches on predicting treatment response without placebo control.

TRIAL REGISTRATION

clinicalTrials.gov Identifier NCT00403520.

摘要

未标注

在法国28个学术中心开展的一项双盲、随机、安慰剂对照的4期试验中，我们确定了海马体（Hp）和基底前脑（BF）体积对于预测遗忘型轻度认知障碍（MCI）患者认知衰退及治疗反应的价值。这些患者每天接受10毫克多奈哌齐或安慰剂治疗，为期12个月，并进行6个月的开放标签随访。结局指标为作为非主要疗效终点的整体及特定领域认知衰退率。分析的意向性治疗（ITT）样本包括215例病例。在线性混合效应模型中，基线Hp体积是整体认知功能变化率的显著预测指标。这种效应与治疗无关。BF体积与整体或特定领域认知衰退率无关。与安慰剂相比，接受多奈哌齐治疗的MCI病例延迟自由回忆衰退率更高。在疑似前驱期阿尔茨海默病（AD）患者中，只有Hp体积而非BF体积是认知衰退的有用预测指标。Hp和BF体积都是治疗反应的较差预测指标，这对以往在无安慰剂对照情况下预测治疗反应的方法提出了质疑。