Interaction entre les émotions et les fonctions exécutives (étude comparative en IRMf chez les témoins et les patients anxieux)

Nous avons étudié en IRMf la relation entre le réseau cérébral des émotions et celui des fonctions cognitives les plus complexes. L'objectif était de vérifier l'hypothèse de " filtrage émotionnel " : pour optimiser l'activation des structures cérébrales impliquées dans les fonctions exécutives (cortex préfrontal dorso-latéral), il est nécessaire de filtrer les signaux émotionnels négatifs pouvant interférer avec les performances. Quinze patients anxieux et quinze témoins ont été inclus. Ces sujets ont effectué un paradigme de mémoire de travail (les épreuves du PASAT) durant l'IRMf. Le paradigme a comporté trois conditions: l'une, moins stressante à intervalle fixe entre les stimuli (PASAT fixe), l'autre plus stressante à intervalle variable (PASAT aléatoire), et une tache contrôle. Des marqueurs psychométriques et neurovégétatifs de l'intensité émotionnelle ont été enregistrés pendant la réalisation du paradigme. La condition PASAT aléatoire engendre plus de stress et fait diminuer les performances. L'activation IRMf montre un profil inverse d'activation entre les témoins et les patients. Chez les témoins il existe une activation optimale durant les deux conditions du PASAT du réseau exécutif dorso-latéral. L'activation de ce réseau est sous optimale chez les patients. Durant la condition PASAT aléatoire, les témoins inhibent le réseau émotionnel orbito-frontal latéral. L'hyperactivité de ce réseau, chez les patients, pourrait être impliquée dans le maintien des affects négatifs, créant des interférences au sein du système exécutif. Ces données suggèrent que le filtrage émotionnel est opérant chez les témoins et inopérant chez les patients.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Clinical Phenotypes in Corticobasal Syndrome with or without Amyloidosis Biomarkers

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Imaging Biomarkers of Neurodegeneration in Alzheimer’s Disease: Distinct Contributions of Cortical MRI Atrophy and FDG-PET Hypometabolism

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Functional connectivity changes differ in early and late-onset alzheimer's disease

International audienceAbstract At a similar stage, patients with early onset Alzheimer's disease (EOAD) have greater neocortical but less medial temporal lobe dysfunction and atrophy than the late‐onset form of the disease (LOAD). Whether the organization of neural networks also differs has never been investigated. This study aims at characterizing basal functional connectivity (FC) patterns of EOAD and LOAD in two groups of 14 patients matched for disease duration and severity, relative to age‐matched controls. All subjects underwent an extensive neuropsychological assessment. Magnetic resonance imaging was used to quantify atrophy and resting‐state FC focusing on : the default mode network (DMN), found impaired in earlier studies on AD, and the anterior temporal network (ATN) and dorso‐lateral prefrontal network (DLPFN), respectively involved in declarative memory and executive functions. Patterns of atrophy and cognitive impairment in EOAD and LOAD were in accordance with previous reports. FC within the DMN was similarly decreased in both EOAD and LOAD relative to controls. However, a double‐dissociated pattern of FC changes in ATN and DLPFN was found. EOAD exhibited decreased FC in the DLPFN and increased FC in the ATN relative to controls, while the reverse pattern was found in LOAD. In addition, ATN and DLPFN connectivity correlated respectively with memory and executive performances, suggesting that increased FC is here likely to reflect compensatory mechanisms. Thus, large‐scale neural network changes in EOAD and LOAD endorse both common features and differences, probably related to a distinct distribution of pathological changes. Hum Brain Mapp 35:2978–2994, 2014. © 2013 Wiley Periodicals, Inc

A Spatial Decision Eye-Tracking Task in Patients with Prodromal and Mild Alzheimer’s Disease

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Prodromal Alzheimer’s Disease Demonstrates Increased Errors at a Simple and Automated Anti-Saccade Task

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SORL1 rare variants: a major risk factor for familial early-onset Alzheimer’s disease

International audienceThe SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history

Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

International audienceObjective: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.Methods: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-β pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models.Results: Amyloid-β positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-β positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid-β positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration-TDP-43 in svPPA (80%), and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%).Interpretation: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-β biomarkers in PPA patients. Ann Neurol 2018;84:737-748