Dufouil Carole, Dubois Bruno, Vellas Bruno, Pasquier Florence, Blanc Frédéric, Hugon Jacques, Hanon Olivier, Dartigues Jean-François, Harston Sandrine, Gabelle Audrey, Ceccaldi Mathieu, Beauchet Olivier, Krolak-Salmon Pierre, David Renaud, Rouaud Olivier, Godefroy Olivier, Belin Catherine, Rouch Isabelle, Auguste Nicolas, Wallon David, Benetos Athanase, Pariente Jérémie, Paccalin Marc, Moreaud Olivier, Hommet Caroline, Sellal François, Boutoleau-Bretonniére Claire, Jalenques Isabelle, Gentric Armelle, Vandel Pierre, Azouani Chabha, Fillon Ludovic, Fischer Clara, Savarieau Helen, Operto Gregory, Bertin Hugo, Chupin Marie, Bouteloup Vincent, Habert Marie-Odile, Mangin Jean-François, Chêne Geneviève
Centre Inserm U1219, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Bordeaux School of Public Health, Université de Bordeaux, 146 rue Léo Saignat, 33076, Bordeaux cedex, France.
CHU de Bordeaux, Pole de sante publique, F-33000, Bordeaux, France.
Alzheimers Res Ther. 2017 Aug 29;9(1):67. doi: 10.1186/s13195-017-0288-0.
The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements.
In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions.
The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E ε4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers worsened with age, whereas differences were not consistent according to sex.
MEMENTO is a large cohort with extensive clinical, neuropsychological and neuroimaging data and represents a platform for studying the natural history of ADRD in a large group of participants with different subtypes of MCI (amnestic or not amnestic) or isolated SCCs.
Clinicaltrials.gov, NCT01926249 . Registered on 16 August 2013.
阿尔茨海默病及相关疾病（ADRD）的自然病史和发病机制仍知之甚少。能够尽早对患者进行仔细检查并采用整合标准化、重复临床研究与前沿生物标志物测量的综合方法的资源非常有限。
在法国全国性的MEMENTO队列研究中，参与者从记忆诊所招募，筛选出孤立性主观认知主诉（SCC）或轻度认知障碍（MCI；定义为测试表现低于年龄、性别和教育水平规范1.5个标准差）且未患痴呆（临床痴呆评定量表[CDR]<1）的患者。基线数据收集包括神经和体格检查以及广泛的神经心理学测试。要纳入MEMENTO队列，参与者必须同意接受脑磁共振成像（MRI）和血液采样。脑氟代脱氧葡萄糖正电子发射断层扫描和腰椎穿刺为可选项目。脑MRI的自动分析包括对全脑、海马体和白质病变体积的评估。
2011年4月至2014年6月招募的2323名参与者平均年龄为71岁（标准差8.7），62%为女性。40%的参与者CDR为0，30%携带至少一个载脂蛋白Eε4等位基因。我们观察到，超过一半（52%）的参与者患有遗忘型轻度认知障碍（17%为单领域aMCI），32%患有非遗忘型轻度认知障碍（16.9%为单领域naMCI），16%患有孤立性SCC。对神经影像标志物与认知类别之间的多变量分析表明，aMCI参与者的影像生物标志物水平比其他参与者更差，而naMCI参与者的标志物水平介于SCC和aMCI之间。aMCI参与者的白质病变负担往往更大。与CDR无关，所有神经影像和神经心理学标志物均随年龄增长而恶化，而性别差异并不一致。
MEMENTO是一个拥有广泛临床、神经心理学和神经影像数据的大型队列，并代表了一个在大量具有不同亚型MCI（遗忘型或非遗忘型）或孤立性SCC的参与者中研究ADRD自然病史的平台。
Clinicaltrials.gov，NCT01926249。于2叭3年8月|6日注册。
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