The Behavioral and Cognitive Executive Disorders of Stroke: The GREFEX Study.

BACKGROUND: Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. METHODS: 237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. RESULTS: Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. CONCLUSIONS: This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients

Author Correction:Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of mitochondrial substrates (Scientific Reports DOI: 10.1038/s41598-017-01678-4)

2 p.- Correction to: Scientific Reports https://doi.org/10.1038/s41598-017-01678-4, published online 10 May 2017Peer reviewe

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

Funder: QingLan Research Project of Jiangsu for Outstanding Young TeachersFunder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical UniversityFunder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical UniversityAbstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population

La plainte mnésique du sujet âgé (à propos du concept de " Mild Cognitive Impairment ")

De par son anatomie, sa biochimie et ses mécanismes d'action, l'étude de la mémoire permet d'appréhender une plainte récurrente en médecine générale chez le sujet âgé : la plainte mnésique. De l'oubli bénin de Kral en 1962 au concept de " Mild Cognitive Impairment " ou MCI de Petersen en 2001, l'idée d'une maladie d'Alzheimer au stade pré-démentiel s'est progressivement imposée. Les patients MCI sont à haut risque de conversion en maladie d'Alzheimer. Ainsi l'étude de marqueurs biologiques et/ou radiologiques précoces prédictifs est nécessaire. En dehors d'essais thérapeutiques en cours ayant pour but d'empêcher la conversion ou d'agir symptomatiquement, il n'y a actuellement aucun traitement envisageable. Les patients MCI nécessitent cependant un suivi médical, neuropsychologique et social annuel en raison du risque d'évolution en maladie d'Alzheimer.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

La dépression du sujet de plus de cinquante ans est-elle une maladie neurodégénérative ? (résultats préliminaires d'un suivi de cohorte)

La dépression survenant après l'age de 50 ans, pose des problèmes diagnostiques et physiopathologiques. Parallèlement, la démence frontotemporale se manifeste fréquemment par une symptomatologie psychiatrique, dont la dépression. De nombreuses similitudes semblent exister entre ces deux pathologies. L'objectif principal de cette étude était d'utiliser une approche évaluative similaire afin de comparer le profil neurologique, neuropsychiatrique et psychiatrique de patients présentant une dépression débutant après 50 ans et de patients présentant une démence frontotemporale, pour tenter de déterminer s'il s'agit ou non de la même affection. Quinze patients ont été inclus dans létude (8 patients DFT et 7 patients dépressifs). Seule la présence d'une symptomatologie dépressive significative différencie les deux groupes de patients. Des altérations frontales spécifiques existent dans les deux groupes, selon des modalités très proches. Sous réserve de l'étude d'un plus large échantillon de patients et du suivi évolutif à plus long terme de la cohorte ainsi formée, il semblerait que certaines dépressions survenant après l'âge de 50 ans soient d'authentiques maladies neurodégénératives, variantes symptomatologiques de DFT.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Identification et validation d’une signature transcriptomique sanguine d’aide au diagnostic de la maladie d’Alzheimer (ACLARUSDX™).

National audienc

Identification et validation d’une signature transcriptomique sanguine d’aide au diagnostic de la maladie d’Alzheimer (ACLARUSDX™).

National audienc

Symptomatic treatments in Alzheimer's disease in 2016: a study from Memory centers in France

International audienc