Multi-dimensional profiling of elderly at-risk for Alzheimer's disease in a differential framework

International audienceThe utility of EEG in Alzheimer’s disease (AD) research has been demonstrated over several decades in numerous studies. EEG markers have been employed successfully to investigate AD-related alterations in prodromal AD and AD dementia. Preclinical AD is a recent concept and a novel target for clinical research. This project tackles two issues: first, AD prediction at the preclinical sta ge, by exploiting the multimodal INSIGHT-preAD database, acquired at the Pitié-Salpetrière Hospital; second, an automatic AD diagnosis in a differential framework, by exploiting another large-scale EEG database, acquired at Charles-Foix Hospital. In this project, we will investigate AD predictors at preclinical stage, using EEG data of only subjective Memory Complainers in order to establish a cognitive profiling of elderly at-risk. We will also identify EEG markers for AD detection at early stages in a di fferential diagnosis context. The correlation between EEG markers and clinical biomarkers will be also assessed for a better characterization of the retrieved profiles and a better understanding on the severity of the cognitive disorder. The exploited larg e-scale complementary data offer the opportunity to investigate the full spectrum of the AD neuro-degeneration changes in the brain, using a big data approach and multimodal patient profiling based on resting-state EEG marker

Interaction entre les cellules microgliales et les neurones dopaminergiques dans la maladie de Parkinson

La maladie de Parkinson (MP) est une affection neurodégénérative dopaminergique (DA) du mésencéphale. Parmi les hypothèses sur les mécanismes de la mort neuronale, la neuroinflammation jouerait un rôle dans la progression neurodégénérative. Toutefois, l'élimination microgliale des neurones apoptotiques constituerait une homéostasie favorable. Les mécanismes impliqués dans l'exécution des neurones DA souffrants et dans leur phagocytose seraient importants pour limiter la neuroinflammation et l'évolution de la mort neuronale. Nous avons étudié l expression de Mfge8 et de DAP12 dans les mésencéphales humain et murin, les conséquences d'une déficience en DAP12 in vitro et in vivo et les conséquences d'une déficience en Mfge8 sur la phagocytose, la réaction gliale et la mort neuronale. D après nos résultats, DAP12 a un effet modeste sur la mort neuronale DA in vitro mais sans effet in vivo. Malgré la présence de la phagocytose des neurones DA, une déficience en Mfge8 n influence ni la perte neuronale, ni la phagocytose ni la réaction gliale. Au total, DAP12 et Mfge8 ne sont pas indispensables à l'élimination des neurones DA et ne sont pas impliqués dans la MPPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Le rôle de la lactadhérine dans la maladie d'Alzheimer

La maladie d Alzheimer (MA) est la première cause de démence chez les personnes âgées, avec notamment des troubles de la mémoire. Elle représente un problème majeur de santé publique compte tenu du vieillissement de la population. Le mécanisme exact de cette maladie neurodégénérative reste encore à élucider. Les dépôts de peptide amyloïde Ab et la dégénérescence neurofibrillaire composée de protéine tau sont deux grandes anomalies neuropathologiques de la MA. Nous nous sommes intéressés aux mécanismes de phagocytose du peptide Ab par les macrophages et les cellules microgliales. Dans ce travail, nous avons étudié en particulier le rôle de la lactadhérine, une protéine extracellulaire exprimée par les macrophages, dans ce processus. Nous avons quantifié son expression dans les cerveaux de patients atteints ou non de la MA, ainsi que dans les différentes cellules impliquées dans cette pathologie. Nos résultats montrent que la lactadhérine est exprimée par les astrocytes et la microglie, mais les neurones n en produisent pas. L expression de l ARNm de la lactadhérine est diminuée de 35% dans les cerveaux de patients MA en comparaison avec des cerveaux contrôles. Son expression est inversement corrélée aux dépôts du peptide Ab dans les plaques séniles. Le déficit ou l inhibition de la lactadhérine diminue la phagocytose du peptide Ab par les macrophages humains in vitro et par les macrophages de souris in vitro et in vivo. En conclusion, la lactadhérine joue un rôle important dans la phagocytose du peptide Ab et son expression est diminuée dans la maladie d Alzheimer. Les troubles de sa production ou de sa fonction pourraient contribuer à la progression de la maladie.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Diagnosis of minimal hepatic encephalopathy in patients with cirrhosis: Should we bury psychometric tests?

International audienceno abstrac

How young is your Muscle? A Machine Learning framework for motor functional assessment with ageing by NMF based analysis of HD-sEMG signal

Abstract Objective With ageing, there are various changes in the autonomic nervous system and a simultaneous decline in the motor functional abilities of the human body. This study falls within the framework improvement of the clinical tools dedicated to the robust evaluation of motor function efficiency with ageing. Method Analysis of HD-sEMG signals recorded from 32 channels during Sit To Stand (STS) test are used for the functional assessment of body muscles. For this purpose, five primary characteristic features, iEMG, ARV, RMS, Skewness, Kurtosis , are employed for the study. A channel clustering approach is proposed based on the parameters using Non Negative Matrix Factorization (NMF). Results The NMF based clustering of the HD-sEMG channels seems to be sensitive toward modifications of the muscle activation strategy with ageing during STS test. Conclusion This manuscript provides a framework for the assessment of Motor Functional Age(MFA) of subjects having a range of chronological from 25 yrs to 75 yrs. The groups were made a decade apart and it was found that the MFA varies with the level of activeness of the muscle under study and a premature ageing is observed according to the change in activation pattern of the HD-sEMG grid

: Todd’s paralysis: a neurologic pitfall to be aware of

International audienceLa paralysie de Todd est définie par une crise comitiale partielle suivie par un déficit neurologique temporaire. Ce déficit, partiel ou complet, est généralement unilatéral et dure entre 30 minutes et plusieurs jours avant résolution complète. Une paralysie de Todd peut aussi se présenter comme un trouble phasique ou un trouble visuel, avec le même caractère temporaire. Il est important de connaître l’existence de ce syndrome pour le distinguer d’un accident vasculaire cérébral accompagné de manifestations épileptiques, car l’approche thérapeutique est évidemment bien différente. Nous rapportons un cas didactique de paralysie de Todd, survenu chez une femme de 77 ans

Perspectives on episodic-like and episodic memory

International audienceEpisodic memory refers to the conscious recollection of a personal experience that contains information on what has happened and also where and when it happened. Recollection from episodic memory also implies a kind of first-person subjectivity that has been termed autonoetic consciousness. Episodic memory is extremely sensitive to cerebral aging and neurodegenerative diseases. In Alzheimer's disease deficits in episodic memory function are among the first cognitive symptoms observed. Furthermore, impaired episodic memory function is also observed in a variety of other neuropsychiatric diseases including dissociative disorders, schizophrenia, and Parkinson disease. Unfortunately, it is quite difficult to induce and measure episodic memories in the laboratory and it is even more difficult to measure it in clinical populations. Presently, the tests used to assess episodic memory function do not comply with even down-sized definitions of episodic-like memory as a memory for what happened, where, and when. They also require sophisticated verbal competences and are difficult to apply to patient populations. In this review, we will summarize the progress made in defining behavioral criteria of episodic-like memory in animals (and humans) as well as the perspectives in developing novel tests of human episodic memory which can also account for phenomenological aspects of episodic memory such as autonoetic awareness. We will also define basic behavioral, procedural, and phenomenological criteria which might be helpful for the development of a valid and reliable clinical test of human episodic memory

Weighted Brain Network Analysis on Different Stages of Clinical Cognitive Decline

This study addresses brain network analysis over different clinical severity stages of cognitive dysfunction using electroencephalography (EEG). We exploit EEG data of subjective cognitive impairment (SCI) patients, mild cognitive impairment (MCI) patients and Alzheimer’s disease (AD) patients. We propose a new framework to study the topological networks with a spatiotemporal entropy measure for estimating the connectivity. Our results show that functional connectivity and graph analysis are frequency-band dependent, and alterations start at the MCI stage. In delta, the SCI group exhibited a decrease of clustering coefficient and an increase of path length compared to MCI and AD. In alpha, the opposite behavior appeared, suggesting a rapid and high efficiency in information transmission across the SCI network. Modularity analysis showed that electrodes of the same brain region were distributed over several modules, and some obtained modules in SCI were extended from anterior to posterior regions. These results demonstrate that the SCI network was more resilient to neuronal damage compared to that of MCI and even more compared to that of AD. Finally, we confirm that MCI is a transitional stage between SCI and AD, with a predominance of high-strength intrinsic connectivity, which may reflect the compensatory response to the neuronal damage occurring early in the disease process