Alzheimers Dement

This study aims to examine whether physical activity moderates the association between biomarkers of brain pathologies and dementia risk. From the Memento cohort, we analyzed 1044 patients with mild cognitive impairment, aged 60 and older. Self-reported physical activity was assessed using the International Physical Activity Questionnaire. Biomarkers of brain pathologies comprised medial temporal lobe atrophy (MTA), white matter lesions, and plasma amyloid beta (Aβ)42/40 and phosphorylated tau181. Association between physical activity and risk of developing dementia over 5 years of follow-up, and interactions with biomarkers of brain pathologies were tested. Physical activity moderated the association between MTA and plasma Aβ42/40 level and increased dementia risk. Compared to participants with low physical activity, associations of both MTA and plasma Aβ42/40 on dementia risk were attenuated in participants with high physical activity. Although reverse causality cannot be excluded, this work suggests that physical activity may contribute to cognitive reserve. Physical activity is an interesting modifiable target for dementia prevention. Physical activity may moderate the impact of brain pathology on dementia risk. Medial temporal lobe atrophy and plasma amyloid beta 42/40 ratio were associated with increased dementia risk especially in those with low level of physical activity

Alzheimers Dement

Introduction: The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory. Methods: We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose-positron emission tomography evaluations. Results: Encoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions. Discussion: The neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied

The INSIGHT cohort: baseline analysis of structural MR imaging in asymptomatic subjects at risk for Alzheimer's disease

International audienc

The cortical lesion pattern of Dysexecutive syndrome in MEMENTO cohort

International audienceObjective: The objective of this study was to investigate the association between cortical thickness and executive functions in the Memento Cohort.Background: Dysexecutive disorders are one early sign of Alzheimer’s disease (AD). Their precise cortical lesion patterns still remain undetermined. Memento cohort is a large French cohort with extensive clinical, neuropsychological and neuroimaging data for studying the natural history of AD in a large group of participants with different subtypes of mild cognitive impairment or isolated subjective cognitive complaints.Design/Methods: We selected from the Memento cohort (Dufouil et al., 2017) all subjects with available region of interest (ROI) cortical thickness data and executive function (verbal fluency and trail making test (TMT)) assessment (n=1924 out of N=2323). Mean MMSE was 28.02 (±1.6), 59.8 % of participants had a Clinical Dementia Rating scale of 0.5, 62.1 % were women. Stepwise linear regression adjusted on age, and education level were achieved to determine reduced brain parenchymal fraction (BPF) and decrease of cortical thickness regions related to both verbal fluency (literal and semantic) and time difference of TMT part B and part A performance (TMTB-At).Results: Semantic fluency was related to BPF and cortical thickness of right supramarginal, right cingulate isthmic and left entorhinal regions (R$^2$=0.133, p=0.0001). Literal fluency was related to BPF and cortical thickness of left pars orbitalis region (R$^2$=0.162, p=0. 0001). TMTB-At was related to cortical thickness of right precuneus and right isthmic cingulate regions (R$^2$=0.142, p=0.0001).Conclusions: The cortical lesion pattern of executive functions was the right supramarginal, right cingulate isthmic, left entorhinal regions, left pars orbitalis and right precuneus. To our knowledge this is the first study to determine precisely, from a large cohort with standardized assessments, the cortical regions related to executive performance

CATI: A Large Distributed Infrastructure for the Neuroimaging of Cohorts

The CATI ConsortiumInternational audienceThis paper provides an overview of CATI, a platform dedicated to multicenter neuroimaging. Initiated by the French Alzheimer’s plan (2008–2012), CATI is a research project called on to provide service to other projects like an industrial partner. Its core mission is to support the neuroimaging of large populations, providing concrete solutions to the increasing complexity involved in such projects by bringing together a service infrastructure, the know-how of its expert academic teams and a large-scale, harmonized network of imaging facilities. CATI aims to make data sharing across studies easier and promotes sharing as much as possible. In the last 4 years, CATI has assisted the clinical community by taking charge of 35 projects so far and has emerged as a recognized actor at the national and international levels

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

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

Additional file 2: Table S1. of Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort

Statistical significance of two-by-two cognitive categories comparisons of baseline characteristics distributions: the MEMENTO cohort. Table S2. Baseline characteristics by age group and sex: the MEMENTO cohort. Table S3. Association between baseline characteristics and number of copies of ε4 allele of APOE genotype: the MEMENTO cohort. (DOCX 47 kb

Additional file 1: of Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort

Description of neuropsychological battery. (DOCX 29 kb