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

Carole Dufouil 1, 2, * Bruno Dubois 3 Bruno Vellas 4 Florence Pasquier 5, 6 Frédéric Blanc 7, 8 Jacques Hugon 9 Olivier Hanon 10, 11, 12 Jean-François Dartigues 2, 13 Sandrine Harston 14 Audrey Gabelle 15 Mathieu Ceccaldi 16 Olivier Beauchet 17 Pierre Krolak-Salmon 18 Renaud David 19, 20 Olivier Rouaud 21 Olivier Godefroy 22 Catherine Belin 23 Isabelle Rouch 24 Nicolas Auguste 25 David Wallon 26 Athanase Benetos 27 Jérémie Pariente 28 Marc Paccalin 29 Olivier Moreaud 30 Caroline Hommet 31 François Sellal 32, 33 Claire Boutoleau-Bretonnière 34 Isabelle Jalenques 35 Armelle Gentric 36 Pierre Vandel 37 Chabha Azouani 3, 38, 39 Ludovic Fillon 3, 38, 39 Clara Fischer 3, 38, 39 Helen Savarieau 2, 1 Gregory Operto 3, 38, 39 Hugo Bertin 40, 41, 38 Marie Chupin 3, 38, 39 Vincent Bouteloup 2, 1 Marie-Odile Habert 40, 41 Jean-François Mangin 42, 38 Geneviève Chêne 2, 1
* Corresponding author
1 Pôle de Santé publique [CHU Bordeaux]
2 BPH - Bordeaux population health
3 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
4 F-CMRR-SF - Fédération des Centres Mémoire de Ressource et de Recherche du Sud de la France [CHU Toulouse]
5 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171
6 CMRR - Centre Mémoire de Ressources et de Recherche [Lille-Bailleul]
7 Centre Mémoire de Ressources et de Recherches [Bordeaux]
8 ICube - Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie
9 Centre de Mémoire de Ressources et de Recherche [Paris Nord]
10 USPC - Université Sorbonne Paris Cité
11 EA 4468 - Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologies
12 Centre de Mémoire de Ressources et de Recherche [Paris Broca]
13 Centre de Mémoire de Ressources et de Recherche [Hôpital Pellegrin, Bordeaux]
14 Centre de Mémoire de Ressources et de Recherche [Hôpital Xavier Arnozan, Bordeaux]
15 CMRR - Centres Mémoire de Ressources et de Recherche [Hôpital Gui de Chauliac, Montpellier]
16 Centre de Mémoire de Ressources et de Recherche [Hôpital La Timone, Marseille]
17 Centre Mémoire de Ressources et de Recherche [CHU Angers]
18 CMRR - Centre Mémoire de Ressources et de Recherche [Lyon]
19 CobTek - Cognition Behaviour Technology
20 CMRR Nice - Centre Mémoire de Ressources et de Recherche [Nice]
21 CMRR Dijon - Centre Mémoire Ressources et Recherche [Dijon]
22 Centre Mémoire de Ressources et de Recherche [CHU Amiens]
23 Clinique de la Mémoire [Hôpitaux Universitaires Paris-Seine-Saint-Denis]
24 Centre Mémoire de Ressources et de Recherche [CHU de Saint-Etienne Hôpital Nord]
25 Centre Mémoire de Ressources et de Recherche [CHU de Saint-Etienne Hôpital de la Charité]
26 Service de neurologie [Rouen]
27 Centre Mémoire de Ressources et de Recherche [CHU de Nancy]
28 Centre Mémoire de Ressources et de Recherche [CHU de Toulouse, Hôpital Purpan]
29 Centre Mémoire de Ressources et de Recherche [CHRU de Poitiers La Miletrie]
30 Centre Mémoire de Ressources et de Recherche [CHU Grenoble Alpes-Site NORD, La Tronche]
31 Centre Mémoire de Ressources et de Recherche [CHRU de Tours Hôpital Bretonneau]
32 Mécanismes Centraux et Périphériques de la Neurodégénérescence
33 Centre Mémoire de Ressources et de Recherche [Hôpitaux Civils de Colmar, Strasbourg]
34 Centre Mémoire de Ressources et de Recherche [CHU de Nantes]
35 Centre Mémoire de Ressources et de Recherche [CHU de Clermont-Ferrand]
36 Centre Mémoire de Ressources et de Recherche [CHRU de Brest]
37 Centre Mémoire de Ressources et de Recherche [CHRU de Besançon]
38 CATI - Centre pour l’Acquisition et le Traitement des Images [Saclay]
39 Sorbonne Université
40 CHU Pitié-Salpêtrière [AP-HP]
41 LIB - Laboratoire d'Imagerie Biomédicale
42 Université Paris-Saclay
Abstract : AbstractBackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionsMEMENTO 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 registrationClinicaltrials.gov, NCT01926249. Registered on 16 August 2013.
Keywords : Neuroimaging Cognitive aging Natural history studies (prognosis) Cohort studies Alzheimer’s disease
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Carole Dufouil, Bruno Dubois, Bruno Vellas, Florence Pasquier, Frédéric Blanc, et al.. Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort. Alzheimer's Research and Therapy, BioMed Central, 2016, 9 (1), pp.67. ⟨10.1186/s13195-017-0288-0⟩. ⟨inserm-01580853v2⟩

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