Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort

Introduction Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension–dementia association are still poorly understood. Methods We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. Results Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. Discussion These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension–dementia association. Highlights Paths of hypertension–cognition association were assessed by structural equation models. The hypertension–cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension–cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.Stopping cognitive decline and dementia by fighting covert cerebral small vessel diseas

Congenital Central Hypothyroidism Caused by a Novel IGSF1 Variant Identified in a French Family

International audienceIntroduction: Congenital central hypothyroidism (CCH) is a rare disorder that can be caused by X-linked mutations in the immunoglobulin superfamily member 1 (IGSF1) gene. Here, we describe four familial cases with a variable presentation due to a novel IGSF1 pathogenic variant. Case Presentation: In the index case, an investigation at birth of a suspected brain-lung-thyroid syndrome surprisingly revealed a central hypothyroidism. Next-generation sequencing uncovered a novel IGSF1 pathogenic variant: a hemizygous single base duplication (G) resulting in a premature stop codon (NM_001555.4: c.2485dup, p.Ala829Glyfs*15). Further family investigations revealed missed neonatal CCH for the older brother who presented with prolonged jaundice (thyroid stimulating hormone 3.06 mUI/L, FT4 9.4 pmol/L, FT3 4.2 pmol/L). It also led to the diagnosis of CCH at 11 months of age for the younger brother, whose thyroid function was considered normal at birth. Neuropsychological evaluations showed no cognitive impairment for the eldest two brothers, but a slightly reduced processing-speed index compared with the other parameters for the oldest. Furthermore, a maternal uncle was diagnosed with biochemical CCH at 34 years of age, despite having few symptoms, and a complete workup revealed prolactin deficiency and macroorchidism. Discussion: This report of a rare case of neonatal CCH caused by IGSF1 deficiency highlights the importance of recognizing the neonatal signs of hypothyroidism to diagnose CCH as early as possible. Our results also show the importance of performing family genetic screening if a pathogenic variant is identified, to properly monitor carriers as CCH may develop over time. We suggest that these families should be followed up in the long term to better understand the natural history of this syndrome and evaluate the need for hormone substitution

Comparison of MRI-based response criteria and radiomics for the prediction of early response to transarterial radioembolization in patients with hepatocellular carcinoma

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VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease

Summary: The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease—MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1 gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability. We developed a computational pipeline, VNtyper, for reliable detection of MUC1 VNTR pathogenic variants and demonstrated its clinical utility in two distinct cohorts: (1) a historical cohort including 108 families with ADTKD and (2) a replication naive cohort comprising 2,910 patients previously tested on a panel of genes involved in monogenic renal diseases. In the historical cohort all cases known to carry pathogenic MUC1 variants were re-identified, and a new 25bp-frameshift insertion in an additional mislaid family was detected. In the replication cohort, we discovered and validated 30 new patients

An overview of Auroral Light Fine Analysis multi-instrumental campaigns carried out from Scandinavia in December 2006 and 2007

abstract EGU2008-A-05311International audienceTwo short-term campaigns were organised by ALFA team with aim to coordinate ground based optical and radars observations with DEMETER passes over Scandinavia. ALFA all-sky camera and photometers were operated from KEOPS/ESRANGE (68° N, 21° E) in 2006 and from KHO/Svalbard (78° N, 16° E) in 2007. Scientific instruments on-board DEMETER were running in “burst“ mode up to 73° and 79° in 2006 and 2007, respectively. SuperDARN and EISCAT radars were operated in special modes in order to provide best temporal and spatial resolution of the ionospheric plasma parameters along the magnetic field lines of DEMETER observations. We present an overview of these campaigns and discuss in details few observations of auroral arcs dynamics. Our objective here is to analyse formation of meso- and small-scale irregularities of electron density along the arcs, relation between density perturbations and intensification of light emissions, mechanisms of acceleration of isolated structures etc

An overview of Auroral Light Fine Analysis multi-instrumental campaigns carried out from Scandinavia in December 2006 and 2007

abstract EGU2008-A-05311International audienceTwo short-term campaigns were organised by ALFA team with aim to coordinate ground based optical and radars observations with DEMETER passes over Scandinavia. ALFA all-sky camera and photometers were operated from KEOPS/ESRANGE (68° N, 21° E) in 2006 and from KHO/Svalbard (78° N, 16° E) in 2007. Scientific instruments on-board DEMETER were running in “burst“ mode up to 73° and 79° in 2006 and 2007, respectively. SuperDARN and EISCAT radars were operated in special modes in order to provide best temporal and spatial resolution of the ionospheric plasma parameters along the magnetic field lines of DEMETER observations. We present an overview of these campaigns and discuss in details few observations of auroral arcs dynamics. Our objective here is to analyse formation of meso- and small-scale irregularities of electron density along the arcs, relation between density perturbations and intensification of light emissions, mechanisms of acceleration of isolated structures etc

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort

International audienceIntroduction: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood.Methods: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data.Results: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers.Discussion: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association.Highlights: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging