Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort

Carole Dufouil, Bruno Dubois, Bruno Vellas, Florence Pasquier, Frédéric Blanc, Jacques Hugon, Olivier Hanon, Jean-François Dartigues, Sandrine Harston, Audrey Gabelle, Mathieu Ceccaldi, Olivier Beauchet, Pierre Krolak-Salmon, Renaud David, Olivier Rouaud, Olivier Godefroy, Catherine Belin, Isabelle Rouch, Nicolas Auguste, David Wallon, Athanase Benetos, Jérémie Pariente, Marc Paccalin, Olivier Moreaud, Caroline Hommet, François Sellal, Claire Boutoleau-Bretonniére, Isabelle Jalenques, Armelle Gentric, Pierre Vandel, Chabha Azouani, Ludovic Fillon, Clara Fischer, Helen Savarieau, Gregory Operto, Hugo Bertin, Marie Chupin, Vincent Bouteloup, Marie-Odile Habert, Jean-François Mangin, Geneviève Chêne, MEMENTO cohort Study Group, Carole Dufouil, Bruno Dubois, Bruno Vellas, Florence Pasquier, Frédéric Blanc, Jacques Hugon, Olivier Hanon, Jean-François Dartigues, Sandrine Harston, Audrey Gabelle, Mathieu Ceccaldi, Olivier Beauchet, Pierre Krolak-Salmon, Renaud David, Olivier Rouaud, Olivier Godefroy, Catherine Belin, Isabelle Rouch, Nicolas Auguste, David Wallon, Athanase Benetos, Jérémie Pariente, Marc Paccalin, Olivier Moreaud, Caroline Hommet, François Sellal, Claire Boutoleau-Bretonniére, Isabelle Jalenques, Armelle Gentric, Pierre Vandel, Chabha Azouani, Ludovic Fillon, Clara Fischer, Helen Savarieau, Gregory Operto, Hugo Bertin, Marie Chupin, Vincent Bouteloup, Marie-Odile Habert, Jean-François Mangin, Geneviève Chêne, MEMENTO cohort Study Group

Abstract

Background: 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.

Methods: 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 18F-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.

Results: 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.

Conclusions: 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.

Trial registration: Clinicaltrials.gov, NCT01926249 . Registered on 16 August 2013.

Keywords: Alzheimer’s disease; Cognitive aging; Cohort studies; Natural history studies (prognosis); Neuroimaging.

Conflict of interest statement

Ethics approval and consent to participate

This study was performed in accordance with the guidelines of the Declaration of Helsinki. The MEMENTO study protocol has been approved by the local ethics committee (“Comité de Protection des Personnes Sud-Ouest et Outre Mer III”; approval number 2010-A01394-35). All participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

FB received speaker’s honoraria and travel expenses from Roche, Biogen Idec, Novartis and Merck Serono. MCe received consultant’s fees from GE Healthcare, Eli Lilly, MSD and Piramal. GC received research support from Avid Radiopharmaceuticals and GE Healthcare. JFD received research support from Ipsen and Roche. BD received consultant’s fees from Eli Lilly and Boehringer-Ingelheim, and he received funding for his institution from Merck, Pfizer and Roche. CD received research support from Avid Radiopharmaceuticals and GE Healthcare. FS received honoraria from Teva, Novartis Pharmaceuticals, Sanofi-Genzyme and Eisai. The other authors declare that they have no competing interests.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
Number of included subjects by centre in the MEMENTO cohort

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