Claudette Pluchon

Activated mTOR and PKR Kinases in Lymphocytes Correlate with Memory and Cognitive Decline in Alzheimer’s Disease

Background: The control of translation, involving the kinases mTOR (mammalian target of rapamycin) and PKR (double-stranded RNA-dependent protein kinase), modulates cell survival and death and is altered in the brains of patients with Alzheimer’s disease (AD). In AD increased susceptibility of lymphocytes to apoptosis has been reported. Methods: We investigated the level of the kinases mTOR and PKR and the eukaryotic initiation factor 2α (eIF2α) in lymphocytes of patients with AD in comparison with controls. In AD patients we also looked for a correlation between activated proteins and cognitive and memory tests. Results: We report significant alterations of the levels of these kinases and eIF2α in lymphocytes of AD patients that were also significantly correlated with cognitive and memory test scores. Conclusion: These results suggest that the levels of mTOR, PKR and eIF2α in lymphocytes could follow the cognitive decline in AD.

Apathy in Parkinson’s Disease: An Electrophysiological Study

In Parkinsons disease (PD), apathy (or loss of motivation) is frequent. Nevertheless, the contribution of attentional disorders to its genesis is still not clearly known. We want to determine the relation existing between apathy and attentional disorders by using P300a (or novelty P3) as a marker of the attentional process. The study included 25 patients (13 women and 12 men) with PD for whom we have determined the relationship between automatic attention (represented by P300a) and motor status, apathy, executive dysfunction, mental flexibility, inhibitory control, and depression/anxiety. We have found a correlation between the apathy score and amplitude of novelty P300 during the ON period and also a correlation of the apathy score with a decrease in amplitude of P300 during the OFF period. In a linear regression model, changes in the P300a predicted the severity of apathy independently of any other variable. We concluded firstly that the reduction in amplitude of the P300a wave was a neurophysiological marker of apathy in PD and secondly that apathy led to both dopaminergic denervation (mesolimbic) and nondopaminergic (dorsolateral prefrontal-subcortical) dysfunction.

Peripheral p70S6k levels and emotional memory in patients with Alzheimer's disease

Alzheimers disease (AD) is clinically marked at the onset, by memory disturbances affecting explicit memory. Emotional explicit memory is enhanced in normal subjects and remained less affected at the beginning of AD. The kinase p70S6k participates in the control of protein translation and seems also implicated in the process of synaptic plasticity and the formation of memory at the molecular level. In a previous study, we have shown that peripheral p70S6k level is correlated with the decline of cognitive and memory functions in patients with AD. The goal of the present study was to analyse emotional and neutral explicit memory in AD patients and to evaluate the levels of active p70S6k in lymphocytes by western blots. The results reveal that the difference between emotional and neutral memories are correlated with the levels of peripheral p70S6k in patients with AD, as well as with the global cognitive scores assessed by the Mini Mental Status Examination. The decline of emotional memory in AD patients is reflected by the decrease of p70S6k levels.

Designing an operating theatre for awake procedures: A solution to improve multimodality information input.

Objective. Many neurosurgical procedures are now performed with the patient aware in order to allow interactions between the patient and healthcare professionals. These procedures include awake brain surgery and spinal cord stimulation (SCS), lead placement for treatment of refractory chronic back and leg pain. Neurosurgical procedures under local anaesthesia require optimal intraoperative cooperation of the patient and all personnel involved in surgery. In addition to accommodating this extra source of intraoperative information all other necessary sources of data relevant to the procedure must be presented. The concept of an operating room dedicated to neurosurgical procedures performed aware and accommodating these concepts is presented, and some evidence for improvements in outcome presented, deriving from a series of patients implanted with spinal cord stimulators before and after the operating theatre was brought into service. Results and discussion. In addition to the description, two videos demonstrate the facility online. Beyond this qualitative evidence, quantitative improvement in patient outcome is evidenced by the series presented: 91.3% of patients operated in the awake anaesthesia-dedicated theatre obtained adequate low back pain coverage, versus 60.0% for patients operated before (p = 0.028). Conclusion. The concept of such an operating room is a step in improving the outcome by improving the presentation of all types of information to the operating room staff most notably in the example of aware procedures.

Troubles de la communication après régression d’une aphasie sous-corticale : disconnexion fronto-sous-corticale ?

Resume Introduction La pragmatique etudie l’adaptation et la pertinence du langage conversationnel qui peuvent etre perturbees meme si les fonctions phonologique, syntaxique et semantique envisagees isolement apparaissent normales. En neuropsychologie de l’adulte, les travaux deja publies s’interessant aux desordres de la fonction pragmatique du langage ne concernent que des sujets ayant des lesions frontales. Methodes Nous rapportons le cas d’un patient droitier dont les troubles du langage initiaux realisant un tableau d’aphasie dissidente en rapport avec un hematome capsulo-lenticulaire gauche se sont progressivement ameliores pour laisser place a des troubles du discours conversationnel qui ont ete analyses selon des indices pragmatiques en situation d’interview libre ou dirigee. Resultats Les resultats ont montre qu’il n’existait de difference entre les deux types d’interview que pour les seuls phenomenes de non-contingences significativement plus nombreux en interview dirigee. Une comparaison effectuee avec le discours de cinq sujets temoins confrontes a des situations identiques a mis en evidence des differences hautement significatives concernant les proximites lexicales originales, les phenomenes de non-contingences et les marqueurs de gene absents du discours des temoins. Discussion et conclusion Les troubles pragmatiques de la conversation remarques notamment en situation d’interview dirigee chez ce patient ont pour certains auteurs ete mis en relation avec l’existence d’un dysfonctionnement des fonctions executives decrit egalement dans cette observation. L’existence de difficultes pour s’adapter aux contraintes conversationnelles du contexte d’interview pourrait par consequent egalement relever d’une disconnexion fronto-sous-corticale en rapport chez ce patient avec l’existence d’une lesion capsulo-lenticulaire gauche.

Rehabilitación de la inatención espacial

En este trabajo, revisamos las estrategias de rehabilitacion de la inatencion espacial en funcion de algunos procesos psicobiologicos afectados, subyacentes a este deficit. Esta revision se centra en distintas tecnicas de rehabilitacion que actuan sobre: a) la vigilancia y el nivel de activacion atencional; b) las referencias espaciales y las representaciones espaciales (las manipulaciones sensoriales) como estimulacion calorica vestibular, estimulacion optocinetica, estimulacion propioceptiva de los musculos de la nuca, metodo de Bon Saint Come, la adaptacion del prisma, etc.; c) el area premotriz y la atencion premotriz (“indicacion espaciomotriz”); d) la orientacion de la mirada mediante entrenamientos de la exploracion visual del espacio, y e) el equilibrio interhemisferico, que usa ejercicios lateralizados para activar o inhibir el hemisferio lesionado o no lesionado, respectivamente. Aunque la mayoria de las tecnicas presentadas ofrecen efectos relativamente positivos, estas no producen una total recuperacion del deficit. Esta revision podria guiarnos en la elaboracion de estudios y programas de rehabilitacion mas sistematizados.

Réactivation automatique en mémoire sémantique de connaissances didactiques au cours du vieillissement normal et dans la maladie d’Alzheimer

Resume Introduction Ce travail a eu pour but d’etudier les aspects les plus consolides de la memoire semantique chez des sujets normaux et des patients ayant une maladie d’Alzheimer (MA). Patients et methode . Une premiere epreuve basee sur la reactivation automatique de connaissances didactiques a ete elaboree. Constituee de 250 expressions verbales automatiques explorant la culture generale, elle a ete validee en fonction de l’âge et du niveau culturel chez 219 sujets temoins (20-90 ans). Une epreuve simplifiee appelee EVA, incluant 50 des 250 items initialement choisis, a ensuite ete construite. Les scores obtenus a l’EVA par la population normale en fonction de l’âge et du niveau culturel ont ete classes en centilages. Les scores obtenus par 20 patients MA a l’EVA, au MMSE et au « Pyramids and Palm Trees Test » (evaluation « classique » de la memoire semantique), ont ensuite ete compares. Resultats . Les resultats montrent que l’augmentation des scores obtenus a l’epreuve initiale par les sujets temoins de meme niveau culturel est significativement correlee a l’accroissement de l’âge. Les resultats obtenus a l’EVA par les temoins montrent que la valeur de la mediane, pour une meme tranche d’âge, est d’autant plus elevee que le niveau culturel est plus eleve. Les scores des patients MA a l’EVA et au MMSE sont significativement correles (resultats d’autant plus faibles que la demence est plus severe) ; il en est de meme pour les scores a l’EVA et au « Pyramids and Palm Trees Test ». Parmi dix patients presentant une demence legere (MMS > 20), 7 obtiennent au « Pyramids and Palm Trees Test » des scores pathologiques. Conclusion . Notre etude confirme donc le fait que les changements lies au vieillissement normal n’affectent pas tous les aspects de la cognition. Les elements les plus consolides de la memoire semantique tels qu’ils sont explores par l’EVA resistent a la deterioration aux stades initiaux de la MA, mais subissent ensuite le meme declin que celui observe pour d’autres aspects de la memoire semantique. L’etude montre aussi que la normalite des performances a une epreuve de ce type n’elimine pas pour autant l’existence d’un trouble de la memoire semantique aux stades initiaux de la MA. Nous proposons donc ici une epreuve qui permet d’explorer certains aspects du stock semantique sans necessairement faire intervenir de processus actif de recuperation. Cette epreuve ne permet pas un diagnostic precoce de la MA. Elle peut, en revanche, contribuer a evaluer la gravite de la maladie au fur et a mesure de l’evolution des troubles.

P3-094: Deficit of emotional memory correlates with levels of the kinase p70S6k in lymphocytes of patients with Alzheimer disease

groups. Complement factor-H (CFH) also showed a significant negative correlation with hippocampal mI/Cr PCr (r -0.33, p 0.04) while alpha2-macroglobulin (A2M) showed a similar but non-significant correlation with hippocampal mI/Cr PCr (r -0.3, p 0.07).When we examined the AD group alone, we found a considerably stronger positive correlation between A2M and NAA/mI (r 0.64, p 0.02), while CFH showed a positive correlation tending to significance (r 0.55, p 0.06). Within the AD group, there was a strong negative correlation between CFH (r -0.63, p 0.02) and A2M (r -0.57, p 0.04) with mI/Cr PCr. Conclusions: Using a combined proteomic-neuroimaging strategy, we identified plasma A2M and CFH as proteins showing significant correlations with hippocampal metabolite ratios known to reflect neurodegeneration in AD.