Refining understanding of working memory buffers through the construct of binding:Evidence from a single case informs theory and clinical practice

International audienceBinding operations carried out in working memory enable the integration of information from different sources during online performance. While available evidence suggests that working memory may involve distinct binding functions, whether or not they all involve the episodic buffer as a cognitive substrate remains unclear. Similarly, knowledge about the neural underpinnings of working memory buffers is limited, more specifically regarding the involvement of medial temporal lobe structures. In the present study, we report on the case of patient KA, with developmental amnesia and selective damage to the whole hippocampal system. We found that KA was unable to hold shape-colours associations (relational binding) in working memory. In contrast, he could hold integrated coloured shapes (conjunctive binding) in two different tasks. Otherwise, and as expected, KA was impaired on three relational memory tasks thought to depend on the hippocampus that are widely used in the early detection of Alzheimer's disease. Our results emphasize a dissociation between two binding processes within working memory, suggesting that the visuo-spatial sketchpad could support conjunctive binding, and may rely upon a large cortical network including sub-hippocampal structures. By contrast, we found evidence for a selective impairment of relational binding in working memory when the hippocampal system is compromised, suggesting that the long-term memory deficit observed in amnesic patients may be related to impaired short-term relational binding at encoding. Finally, these findings may inform research on the early detection of Alzheimer's disease as the preservation of conjunctive binding in KA is in sharp contrast with the impaired performance demonstrated very early in this disease

Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from cortical dementias

International audienceBackground: Considering that most of semantic dementia (SD) and frontotemporal dementia (FTD) patients show no postmortem Alzheimer's disease (AD) pathology, cerebrospinal fluid (CSF) biomarkers may be of value for distinguishing these patients from those with AD. Additionally, biomarkers may be useful for identifying patients with atypical phenotypic presentations of AD, such as posterior cortical atrophy (PCA) and primary progressive non-fluent or logopenic aphasia (PNFLA). Methods: We investigated CSF biomarkers (beta-amyloid 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau [P-tau]) in 164 patients with AD (n=60), PCA (n=15), behavioral variant FTD (n=27), SD (n=19), (PNFLA) (n=26) and functional cognitive disorders (FCD, n=17). We then examined the diagnostic value of these CSF biomarkers in distinguishing the patients from those with AD. Results: The P-Tau/Aβ42 ratio was found to be the best biomarker for discriminating AD from FTD and SD, with a sensitivity of 91.7% and 98.3%, respectively, and a specificity of 92.6% and 84.2%, respectively. As expected, biomarkers were less effective in differentiating AD from PNFLA and PCA, as significant proportions of PCA and PNFLA patients (60% and 61.5%, respectively) had concurrent alterations of both T-tau/Aβ42 and P-Tau/Aβ42 ratios. None of the FCD patients had a typical AD CSF profile or abnormal T-tau/Aβ42 or P-Tau/Aβ42 ratios. Conclusion: The P-Tau/Aβ42 ratio is a useful tool to discriminate AD from both FTD and SD, which are known to involve pathological processes distinct from AD. Biomarkers could be useful for identifying patients with an atypical AD phenotype that includes PNFLA and PCA

Les médecins traitants face aux syndromes démentiels (applicabilité des recommandations de la Haute Autorité de Santé)

Introduction: Les médecins généralistes sont amenés, du fait du vieillissement de la population, à prendre en charge un nombre croissant de patients concernés par les syndromes démentiels. Cette prise en charge se révèle toutefois difficile le médecin généraliste intervenant bien sûr dans le champ médical mais également dans les champs sociaux et juridiques. C'est pourquoi la Haute Autorité de Santé a émis en décembre 2011 de nouvelles recommandations sur le diagnostic et la prise en charge de la maladie d'Alzheimer et maladies apparentées, redéfinissant le rôle du médecin traitant tout au long du parcours de soins de ces patients, le qualifiant de pivot de l'organisation des soins. Matériel et Méthodes: Une méthode de recherche qualitative de type focus groups a été utilisée auprès de médecins généralistes du bassin rennais. Deux focus groups constitués respectivement de 8 et 5 médecins généralistes ont été constitués en fin d'année 2013. Résultats: Aucun n'a eu connaissance des dernières recommandations de la Haute Autorité de Santé. Les données recueillies montrent les nombreuses difficultés rencontrées par les médecins généralistes, qu'il s'agisse de l'évaluation clinique initiale ou de la coordination de soins avec les différents acteurs du secteur médico-social. Au-delà d'un simple manque de formation, l'absence de perspective thérapeutique semble constituer un frein à l'intérêt qu'ils portent à ces patients. Les dernières recommandations semblent perçues comme compliquant la prise en charge de ces derniers. Discussion: L'applicabilité des dernières recommandations pose question. Les médecins traitants rencontrés les jugent complexes, doutant de leur intérêt pour leurs patients. La formation initiale des médecins généralistes devrait sans doute être repensée pour permettre à long terme au praticien d'être réellement dans la coordination. On pourrait également se demander si les recommandations de la HAS sont un bon outil pour faire évoluer les pratiques des soignants et devraient probablement plus intégrer la notion de poly-pathologie et d'individualisation afin d'optimiser la prise en charge des personnes âgées dans les années à venir.RENNES1-BU Santé (352382103) / SudocSudocFranceF

L’effet des informations de surface sur la dénomination orale d’images : un artéfact ? Apport des analyses intra-individuelles

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Increased cognitive asymmetries detects prodomal Alzheimer's disease

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When the zebra loses its stripes but is still in the savannah: results from a semantic priming paradigm in semantic dementia.

International audienceStudies using semantic priming paradigms to measure the integrity of the features underlying concepts in semantic dementia (SD) reported differential impairment, in that functional features appeared to be more robust to brain damage than other features, such as perceptual ones. However, these prior studies were single case reports and the inclusion of too many heterogeneous features under the "functional features" heading casts doubts on their apparent preservation. To verify the robustness of functional features compared with perceptual ones, we carried out a group study where we deliberately restricted the exploration of semantic features to two clearly defined types of attribute: visuoperceptual ("visual") versus contextual-functional ("contextual"). We administered an implicit lexical-decision priming task to 8 SD patients and 31 healthy matched controls, at baseline. Four of the patients underwent a follow-up assessment at one year. For controls, we found a significant priming effect in the visual condition, but not in the contextual one, whereas the SD group exhibited the reverse pattern of performances. The follow-up data provided evidence of the robustness of the dissociation between priming performances in the two attribute conditions. The fact that a particular priming effect was observed in the SD patients but not in controls could be regarded as a sign of semantic disequilibrium. Since perceptual features have been shown to be a core determinant of similarity-based/taxonomic relationships, whereas complementary-based/thematic processing relies mainly on contextual relationships, we interpreted our findings in terms of the differential recruitment of one of the two systems of semantic relationships (taxonomic vs. thematic). Moreover, these two distinct and parallel systems have previously been reported to coexist - and compete - in healthy adults. We thus argue that controls automatically drew on similarity-based/taxonomic relationships, leading to a significant priming effect for visual features but not for contextual ones. By contrast, their impaired perceptual features forced the SD patients to resort to the system of thematic relationships

L'apprentissage en mémoire de reconnaissance: La répétition de la récupération, pas de l'encodage, optimise la rétention

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De la psychométrie au handicap neuropsychologique dans la sclérose en plaques. Proposition d’une batterie de dépistage en langue française et facteurs de risque cognitifs [From psychometry to neuropsychological disability in multiple sclerosis: a new brief French cognitive screening battery and cognitive risk factors].

International audienceINTRODUCTION: Cognitive deficit in multiple sclerosis (MS) is a frequent early feature in the disease course, which conditions patients' overall disability. The goals of this study were to validate a reproducible brief screening battery written in French and to examine cognitive risk profiles in patients with a mild physical disability. METHODS: Cognitive performances of 40 patients with EDSS 40 years, pathological laughing-crying, unemployment. CONCLUSIONS: Our brief battery is an easy and reproducible tool. Completed with warning signs indicating the need for neuropsychological screening, this tool provides the practitioner with a global means of assessing disease activity and potentially therapeutic efficacy

Towards a Left MTL Specialization for Arbitrary-Associative Learning? A Multiple-Case Study

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