Spatial distribution of cerebral white matter lesions predicts progression to mild cognitive impairment and dementia

CONTEXT White matter lesions (WML) increase the risk of dementia. The relevance of WML location is less clear. We sought to determine whether a particular WML profile, based on the density and location of lesions, could be associated with an increased risk of mild cognitive impairment (MCI) or dementia over the following 7 years. METHODS In 426 healthy subjects from a cohort of community-dwelling people aged 65 years and over (ESPRIT Project), standardized cognitive and neurological evaluations were repeated after 2, 4 and 7 years. Patterns of WML were computed with a supervised data mining approach (decision trees) using the regional WML volumes (frontal, parietal, temporal, and occipital regions) and the total WML volume estimated at baseline. Cox proportional hazard models were then constructed to study the association between WML patterns and risk of MCI/dementia. RESULTS Total WML volume and percentage of WML in the temporal region proved to be the best predictors of progression to MCI and dementia. Specifically, severe total WML load with a high proportion of lesions in the temporal region was significantly associated with the risk of developing MCI or dementia. CONCLUSIONS Above a certain threshold of damage, a pattern of WML clustering in the temporal region identifies individuals at increased risk of MCI or dementia. As this WML pattern is observed before the onset of clinical symptoms, it may facilitate the detection of patients at risk of MCI/dementia.The ESPRIT Project is financed by the regional government of Languedoc-Roussillon (http://www.laregion.fr), the Agence Nationale de la Recherche (ANR: http://www.agence-nationale-recherche.fr) and an unconditional grant from Novartis (http://www.novartis.fr). This study is also supported by France Alzheimer (http://www.francealzheimer.org/)

Mean Arterial Pressure Change Associated with Cerebral Blood Flow in Healthy Older Adults

We investigate over a 12-year period the association between regional cerebral blood flow (CBF) and cardiovascular risk factors in a prospective cohort of healthy older adults (81.96 +/- 3.82 year-old) from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) study. Cardiovascular risk factors were measured over 12 years, and gray matter CBF was measured at the end of the study from high-resolution magnetic resonance imaging using arterial spin labeling. The association between cardiovascular risk factors, their long-term change, and CBF was assessed using multivariate linear regression models. Women were observed to have higher CBF than men (p < 0.05). Increased mean arterial pressure (MAP) over the 12-year period was correlated with a low cerebral blood flow (p < 0.05, R(2) = 0.21), whereas no association was detected between CBF and MAP at the time of imaging. High levels of glycemia tended to be associated with low cerebral blood flow values (p < 0.05). Age, alcohol consumption, smoking status, body mass index, history of cardiovascular disease, and hypertension were not associated with CBF. Our main result suggests that change in MAP is the most significant predictor of future CBF in older adults

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&amp;cond=depression&amp;cntry=FR&amp;rank=

Fluoroprophylaxie des dents en territoire irradié (analyse de la littérature)

Les cancers des voies aéro-digestives ont une incidence élevée en France. La radiothérapie, la chirurgie et la chimiothérapie constituent les traitements principaux de ces cancers. La radiothérapie induit une diminution quantitative et une modification qualitative de la salive, ce qui a pour conséquence une incidence carieuse élevée. Une analyse de la littérature est effectuée, afin de déterminer la méthode de fuoroprophylaxie la plus efficiente chez les patients irradiés ayant eu un cancer des VADS. Le suivi et l'observance des patients vis-à-vis de leur traitement fluoré sont aussi évalués. Au vue de la revue de la littérature, l'application de gel fluoré au moyen de gouttières de fluoration semble être considérée comme la méthode la plus efficace pour prévenir les caries post-radiques. Cependant, seulement la moitié des patients irradiés sont observants vis-à-vis de leur traitement fluoré.NANTES-BU Médecine pharmacie (441092101) / SudocNANTES-Bib.Odontologie (441092219) / SudocSudocFranceF

Validation of a quantitative susceptibility mapping acquisition and reconstruction pipeline using a new iron sucrose based MR susceptibility phantom.

International audienceQuantitative susceptibility mapping is a new technique and its processing pipeline has to be validated before clinical practice. We described an easy to build magnetic resonance (MR) susceptibility phantom based on iron sucrose

Recommandations pour la mise en place d’études multicentriques avec IRM

International audienceMRI is becoming increasingly important in clinical research studies, both in terms of inclusion criteria and endpoints. Markers based on MRI acquisitions are now regularly considered as primary endpoints. Especially in multicentre studies, the management of MRI acquisitions has to take into account the heterogeneity of MRI systems in terms of manufacturers, magnetic fields, coils and software versions. This is due to the number of important parameters that can be specified and optimised to obtain MR images, the variability between the solutions proposed by the manufacturers and the regular technical innovations. The aim of this article is to detail the steps and the people to involve in order to carry out an MRI study. Based on the experience and expertise of the members of the Réseau d’entraide multicentrique en IRM (REMI), we propose detailed recommendations to the French-speaking community, in order to better take into account the specificities of MRI at all stages of the study and to participate in improving the quality of MRI research. These recommendations also take into account the specificities of MRI research platforms and clinical imaging services, as well as regulatory constraints.L’IRM prend une place de plus en plus grande dans les études de recherche clinique, que ce soit au niveau des critères d’inclusion ou des critères d’évaluation. Des marqueurs basés sur l’exploitation des acquisitions IRM sont désormais considérés régulièrement comme critères principaux d’évaluation. Dans le cadre d’études multicentriques en particulier, la gestion des acquisitions IRM doit considérer l’hétérogénéité des systèmes IRM en termes de constructeurs, de champs magnétiques, d’antennes de réception et de versions logicielles. Cela s’explique par le nombre de paramètres importants qu’il est possible de spécifier pour obtenir une acquisition IRM, la variabilité entre les solutions proposées par les constructeurs et les innovations techniques régulières. L’objectif du présent article est de détailler les spécificités à prendre en compte et les personnes à impliquer pour réaliser une étude en IRM quel que soit l’organe concerné par l’imagerie. En s’appuyant sur l’expérience et l’expertise des membres du Réseau d’entraide multicentrique en IRM (REMI), nous proposons à la communauté francophone des recommandations détaillées, afin de mieux prendre en compte les spécificités de l’IRM à toutes les étapes de l’étude et de participer à l’amélioration de la qualité de la recherche en IRM. Ces recommandations prennent également en compte les spécificités des plateformes de recherche en IRM et des services d’imagerie clinique, ainsi que les contraintes réglementaires

Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper

Prefrontal activation in suicide attempters during decision making with emotional feedback

International audienceEmotional feedback, such as faces showing emotions, can influence decision making. Decision making and emotional face processing, mainly mediated by the prefrontal and cingulate cortices, are impaired in suicide attempters. Here, we used functional MRI (fMRI) to study prefrontal activation in suicide attempters during a modified version of the Iowa Gambling Task (IGT) that included emotional face feedback. We randomly distributed the 116 euthymic women ( n = 45 suicide attempters, n = 41 affective controls with history of depression without suicide attempt, and n = 30 healthy controls) included in the study in three emotional IGT groups: concordant (safe and risky choices followed by happy and angry faces, respectively), discordant (safe and risky choices followed by angry and happy faces, respectively), and neutral condition (safe and risky choices followed by neutral faces). Considering the two IGT phases (ambiguous and risky), we then analyzed five regions of interest during the risky vs. safe choices: orbitofrontal (OFC), anterior cingulate (ACC), ventrolateral (VLPFC), medial (MPFC) and dorsal prefrontal (DPFC) cortices. We found: (1) impaired decision making and increased DPFC and OFC activation in suicide attempters vs. controls in the discordant condition during the risky phase; (2) reduced VLPFC activation in suicide attempters in the concordant condition during the ambiguous phase; and (3) decreased OFC, ACC and DPFC activation in both control groups in the concordant condition during the ambiguous phase. Suicide attempters showed prefrontal alterations during reward-learning decision making with emotional feedback. Suicide attempters may guide their decisions to avoid social negative feedback despite the expected outcome

Quantitative assessment of near-infrared spectroscopy time course under hypercapnia using an a priori model-based fitting

International audienc