Le TOP 12 : comment interpréter les réponses comme des mesures de la capacité de la mémoire collective ?

International audienceIntroduction. Le TOP 12 évalue la mémoire collective au travers d'une série de huit types de questions portant sur le souvenir de la vie de 12 célébrités nommément désignées. La validation de tels tests est souvent envisagée dans le seul but de prédire un critère externe au test (validation externe) ; la validation interne n'est quant à elle que très rarement étudiée. Objectifs. Montrer comment les réponses obtenues peuvent mesurer une seule grandeur hypothétique (appelée aussi construit) : la capacité de la mémoire collective. Méthodes. L'échantillon est composé de 145 sujets (91 témoins, 32 patients présentant une maladie d'Alzheimer, 21 patients ayant un trouble cognitif léger de type amnésique, 1 patient ayant une démence sémantique). Deux étapes sont nécessaires : modéliser les réponses aux items à l'aide d'un modèle de réponse à l'item à trois paramètres et tester l'unidimensionnalité des scores estimés. Résultats. Les huit modèles s'ajustent étroitement aux données. L'analyse factorielle confirmatoire ne permet pas de rejeter l'idée selon laquelle les huit types de questions mesurent bien une seule et unique grandeur hypothétique. Conclusion. La modélisation psychométrique des données observées avec le TOP 12 indique qu'elles mesurent la capacité de la mémoire collective. Mots clés : mémoire collective * TOP 12 * validation interne * modélisation psychométrique * grandeur hypothétiqu

Le TOP 12 : comment s'en servir pour repérer une pathologie du vieillissement cognitif ?

International audienceIntroduction. Le TOP 12 examine la mémoire collective simplement et rapidement par huit types de question portant sur le souvenir de la vie de 12 célébrités nommément désignées. Objectifs. Vérifier la corrélation entre les scores moyens et le degré de sévérité de la pathologie ; déterminer un seuil permettant de conjecturer sur l'état de la personne au vu de son score au test. Méthodes. L'échantillon est composé de 145 sujets (91 témoins, 32 patients présentant une maladie d'Alzheimer, 21 patients ayant un trouble cognitif léger de type amnésique ou MCIa, 1 patient ayant une démence sémantique). Les propriétés diagnostiques du TOP 12 ont pu être mises en avant en confrontant deux méthodologies : le centilage et la courbe Receiver Operator Characteristic (ROC). Résultats. L'ordre des moyennes et l'ordre des niveaux de gravité pathologique des groupes sont corrélés. Le seuil qui optimise le compromis entre la sensibilité (Se) et la spécificité (Sp) est donné par la méthodologie de la courbe ROC (83 points ; Se = 0,83 ; Sp = 0,70). Le cinquième centile s'avère non optimal étant donné qu'il majore les omissions. Conclusion. Cette validation externe du TOP 12 montre l'intérêt de la méthodologie de la courbe ROC. Mots clés : mémoire collective * TOP 12 * propriétés diagnostiques * centilage * courbe RO

Evolution of Total and Integrated HIV-1 DNA and Change in DNA Sequences in Patients with Sustained Plasma Virus Suppression

AbstractBlood samples from patients with plasma HIV-1 RNA <20 copies/ml for more than 2 years were studied. Significant decreases in total and integrated HIV-1 DNA were observed during the first 15 months of suppressive therapy before the concentrations became stable. Clonal analysis of HIV-1 pol demonstrated that the proportions of resistance mutations in DNA sequences after 2 years were lower than those in baseline DNA and RNA sequences. The changes in the clonal composition of HIV-1 env populations in three patients with evidence of changes in HIV-1 pol populations indicated a shift from predominantly R5-like viruses to predominantly X4-like viruses in two patients and the persistence of predominantly X4-like viruses in the third. Our analyses indicate the reemergence of ancestral sequences from long-lived cells or the residual production of wild-type virus from anatomic sites with limited access to antiretroviral drugs and the preferential infection of cells expressing CXCR4

Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve

Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63–72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met

Corrélations comportementales et neurpsychologiques dans le démence fronto-temporale (étude en tomographie d'émission monophotonique de 16 patients)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

[Functional neuroimaging and the treatment of aphasia: speech therapy and repetitive transcranial magnetic stimulation]

International audienceFunctional imaging has provided new evidence of the neurobiological impact of the treatment of aphasia, including speech therapy, through the alteration of the activated language neural network. In such a way, speech therapy has proved its impact. The role of each hemisphere is still very unclear. Some of the authors link the left-lateralisation of activations to the therapeutic improvement of language and the right-activated network to a maladaptative strategy, whereas others consider the latter as a useful compensatory network for speech disorders. Repetitive trans-cranial magnetic stimulation (rTMS), first used to determine cortical activity, is now used to directly interfere with cerebral activity. In the years to come, rTMS should be developed as an adjuvant therapy for aphasia

Reconciling west nile virus with the autophagic pathway

© 2015, Taylor & Francis Group, LLC. West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for recurrent outbreaks of meningitis and encephalitis. Several studies analyzing the interactions of this pathogen with the autophagic pathway have reported opposite results with evidence for and against the upregulation of autophagy in infected cells. In this regard, we have recently reported that minimal genetic changes (single amino acid substitutions) in nonstructural proteins of WNV can modify the ability of the virus to induce autophagic features such as LC3 modification and aggregation in infected cells. We think that these results could help explain some of the previously reported discrepancies. These findings could also aid in deciphering the interactions of this pathogen with the autophagic pathway at the molecular level aimed to develop feasible antiviral strategies to combat this pathogen, and other related flaviviruses.INIA (RTA2011-0036 and E-RTA2013-00013-C01) and the Comunidad Autónoma de Madrid PLATESA (P2013/ABI-2906)Peer Reviewe

Abnormal outer hair cell efferent innervation in Hoxb1-dependent sensorineural hearing loss.

Autosomal recessive mutation of HOXB1 and Hoxb1 causes sensorineural hearing loss in patients and mice, respectively, characterized by the presence of higher auditory thresholds; however, the origin of the defects along the auditory pathway is still unknown. In this study, we assessed whether the abnormal auditory threshold and malformation of the sensory auditory cells, the outer hair cells, described in Hoxb1null mutants depend on the absence of efferent motor innervation, or alternatively, is due to altered sensory auditory components. By using a whole series of conditional mutant mice, which inactivate Hoxb1 in either rhombomere 4-derived sensory cochlear neurons or efferent motor neurons, we found that the hearing phenotype is mainly reproduced when efferent motor neurons are specifically affected. Our data strongly suggest that the interactions between olivocochlear motor neurons and outer hair cells during a critical postnatal period are crucial for both hair cell survival and the establishment of the cochlear amplification of sound

Good recovery from aphasia is also supported by right basal ganglia: a longitudinal controlled PET study. EJPRM-ESPRM 2008 award winner.

International audienceAIM: It has long been a matter of debate whether recovery from aphasia after left perisylvian lesion is mediated by perilesional left hemispheric regions or by right homologous areas. To investigate the neural substrates of aphasia recovery, a longitudinal study in patients after a left single perisylvian stroke was performed. METHODS: Thirteen aphasic patients were H2(15)O PET-scanned twice at a one year interval during a word generation task. Patients are divided into two groups according to language performance for the word generation task at PET2. For the Good Recovery (GR) group, patients' performances are indistinguishable from those of normal subjects, while patients from the Poor Recovery (PR) group keep language disorders. Using SPM2, Language-Rest contrast is computed for both groups at both PET stages. Then, Session Effect contrast (TEP2-TEP1>0) is calculated for both groups. RESULTS: For the GR group, the Session Effect contrast shows an increase of activations in the left Postero-Superior Temporal Gyrus PSTG but also in the right thalamus and lenticular nuclei; for PR patients, the right lenticular nucleus activation is more important at PET1 than PET2. CONCLUSIONS: The crucial role of the left temporal activation is confirmed and its increase is linked to behavioural recovery. The role of the right basal ganglia to support good recovery from aphasia is a new finding. Their activation may be more task-dependant and related to inhibition of the right frontal cortex