Suchergebnisse

Hauptbeschreibung: Das große Referenz- und Facharztbuch zur klinischen Neurologie liegt hiermit unter der Federführung der international renommierten Herausgeber und der Mitarbeit von über 140 Fachexperten als eine vollständig überarbeitete und erweiterte Neuauflage vor. Durch die thematische Neuausrichtung einzelner Beiträge, z. B. zur transienten globalen Amnesie oder zu Tropenkrankheiten, und acht zusätzliche Kapitel, nämlich zu Antikörper-assoziierten Enzephalopathien, mitochondrialen Erkrankungen, atypischem Gesichtsschmerz, craniomandibulärer Dysfunktion, Hypophysentumoren, Tic/Tourette u

The Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCGEN.118.002115 ; BACKGROUND: Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke and coronary artery disease. However, deciphering their underlying mechanisms are challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for large artery ischemic stroke and coronary artery disease relate to plaque characteristics is thus far unknown but may point to novel mechanisms. METHODS: We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in 2 independent biobanks, Biobank of Karolinska Endarterectomy and Stockholm Atherosclerosis Gene Expression. RESULTS: A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, P=5.09×10-6 after correction for multiple testing. We further characterized this 7q22 Locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood and provide data from public resources showing an association with decreased LDL (low-density lipoprotein) and increase HDL (high-density lipoprotein) in the blood. CONCLUSIONS: Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics. ; Dr van der Laan is funded through grants from the Netherlands CardioVascular Research Initiative of the Netherlands Heart Foundation (CVON 2011/B019 and CVON 2017-20: Generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS I&II]) and the Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001). Drs van der Laan and Haitjema are both funded through the FP7 EU project CVgenes@target (HEALTH-F2-2013–601456). Dr Siemelink is funded by the European Union (BiomarCaRE, grant number: HEALTH-2011–278913), and the technology foundation Stichting voor de Technische Wetenschappen through the Danone partnership program (Project 11679). The UCL Hospitals NIHR Biomedical Research Centre and the Dutch Heart Foundation (Junior Staff Member 2014T001) supported by Dr Asselbergs. The BiKE study was conducted with support from the Swedish Heart and Lung Foundation, the Swedish Research Council (K2009-65X-2233-01-3, K2013-65X-06816-30-4, and 349-2007-8703), Uppdrag Besegra Stroke (P581/2011–123), the Strategic Cardiovascular Programs of Karolinska Institutet and Stockholm County Council, the Stockholm County Council (ALF2011-0260 and ALF-2011-0279), the Foundation for Strategic Research and the European Commission (CarTarDis). ; Peer-reviewed ; Publisher Version

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.

Additional grant support pilot study cohorts: The CODECS study is supported by a grant from Stichting Coolsingel, the Netherlands. Funding for the PROCRAS study was obtained through ZonMw as part of the 'TopZorg' project in 2015 (grant # 842003011). The CU-STRIDE study was funded by the Health and Health Services Research Fund (0708041) of the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region. The CU-RISK study was funded by General Research Fund (grant number GRF CUHK 471911), the National Key Research and Development Program of China (grant number 2016YFC1300600), and the Lui Che Woo Institute of Innovative Medicine, and Therese Pei Fong Chow Research Center for Prevention of Dementia (in memory of Donald H. K. Chow). The Mild Stroke Study 2 was funded by the Wellcome Trust (WT088134/Z/09/A), the Row Fogo Charitable Trust and Chest Heart & Stroke Scotland (long-term follow-up, ref no: Res14/A157). J.M.W. is supported by the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease (ref no. 16 CVD 05) and the UK Dementia Research Institute at The University of Edinburgh. O.K.L.H. is supported by the College of Medicine and Veterinary Medicine at the University of Edinburgh and the Wellcome Trust. ; Peer reviewed ; Publisher PDF

BACKGROUND: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS: We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS: Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD. ; The individual study sponsor(s) had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Dr. Isgum is supported by research grants from Pie Medical Imaging, 3Mensio Medical Imaging B.V., the NWO and Foundation for Technological Sciences under Project 12726, The Netherlands Organization for Health Research and Development, and the Dutch Cancer Society. Dr. Arpegård has received funding through the Stockholm County Council (combined clinical residency and PhD training program). Dr. Amouyel has received personal fees from Servier, Hoffman Laroche, Total, Genoscreen, Alzprotect, Fondation Plan Alzheimer, and Takeda outside of the submitted work; and has shares in Genoscreen. Dr. Morris is a Wellcome Trust Senior Fellow in Basic Biomedical Science under grant number WT098017. Dr. Worrall has received compensation for his role as deputy editor of the Journal of Neurology; and has received National Institutes of Health funding through the National Institute of Neurological Disorders and Stroke (U-01 NS069208) and National Human Genome Research Institute (U-01 HG005160). Dr. Samani is supported by the British Heart Foundation (BHF); and is a National Institute for Health Research Senior Investigator. Dr. Nelson is supported by the BHF. Dr. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA; Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Dr. Patel is supported by a BHF Intermediate Fellowship. Dr. Koenig has received funds through NGFNplus, project number 01GS0834; has received research grants from Abbott, Roche Diagnostics, Beckmann, and Singulex; has received honorarium for lectures from AstraZeneca, Novartis, Merck Sharp & Dohme, Amgen, and Actavis; and has served as a consultant for Novartis, Pfizer, The Medicines Company, Amgen, AstraZeneca, Merck Sharp & Dohme, and GlaxoSmithKline. Dr. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Dr. Svensson has received a grant from the Swedish Society of Medicine (SLS-412071). Dr. Kivimaki has received funding through the Medical Research Council (K013351), Economic and Social Research Council, and National Institutes of Health (HL36310). Dr. Dehghan is supported by a Netherlands Organization for Scientific Research (NWO) grant (VENI, 916.12.154) and the EUR Fellowship; and has received consultancy and research support from Metagenics Inc. (outside the scope of this work). Dr. Ingelsson is supported by grants from Göran Gustafsson Foundation, Swedish Heart-Lung Foundation (20140422), Knut and Alice Wallenberg Foundation (Knut och Alice Wallenbergs Stiftelse), European Research Council (ERC-StG-335395), Swedish Diabetes Foundation (Diabetesfonden; grant no. 2013-024), and the Swedish Research Council (VR; grant no. 2012-1397). Dr. de Bakker is an employee of Vertex Pharmaceuticals. Dr. Ärnlöv was funded by the Swedish Research Council (2012-1727, 2012-2215), Swedish Heart-Lung Foundation, Thuréus Foundation, the Marianne and Marcus Wallenberg Foundation, Dalarna University, and Uppsala University. Dr. Asselbergs is supported by a Dekker scholarship-Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals National Institute for Health Research Biomedical Research Centre. The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement n° HEALTH-F2-2013-601456 (CVgenes-at-target). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. ; Peer-reviewed ; Publisher Version

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

16 páginas, 5 figuras ; Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease. ; The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria "La Caixa", Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—"Una manera de hacer Europa"). Some control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). 100-Plus study: We are grateful for the collaborative efforts of all participating centenarians and their family members and/or relations. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW project number 733050814, 733050512) and Stichting VUmc Fonds. Genotyping of the 100-Plus Study was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The authors are grateful to all LASA participants, the fieldwork team and all researchers for their ongoing commitment to the study. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND) and also funded by Inserm, Institut Pasteur de Lille, the Lille Métropole Communauté Urbaine, the French government's LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Genotyping of the German case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND (German Federal Ministry of Education and Research, BMBF: 01ED1619A). Full acknowledgments for the studies that contributed data can be found in the Supplementary Note. We thank the numerous participants, researchers, and staff from many studies who collected and contributed to the data. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i–Select chips was funded by the French National Foundation on AD and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer's Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIA/NHLBI grants AG049505, AG058589, HL105756 and AGES contract N01–AG–12100, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC–10–196728. This research has been conducted using the UK Biobank public resource obtained through the University of Edinburg Data Share (https://datashare.is.ed.ac.uk/handle/10283/3364). ; Peer reviewed