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51. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W., Luciano, Michelle, Hill, W. David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C. M., Okely, Judith A., Ahola-Olli, Ari V., Barnes, Catriona L. K., Bertram, Lars, Bis, Joshua C., Burdick, Katherine E., Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E., Hayward, Caroline, Hofer, Edith, Ikram, M. Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A., Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V., Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, van der Lee, Sven J., Ware, Erin B., Windham, B. Gwen, Wright, Margaret J., Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A., Armstrong, Nicola J., Assareh, Amelia A., Attia, John R., Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A., Böhmer, Anne C., Boyle, Patricia A., Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D., Cirulli, Elizabeth T., Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R., Dale, Anders M., Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G., Evangelou, Evangelos, Faul, Jessica D., Ford, Ian, Freimer, Nelson A., Gao, He, Giegling, Ina, Gillespie, Nathan A., Gordon, Scott D., Gottesman, Rebecca F., Griswold, Michael E., Gudnason, Vilmundur, Harris, Tamara B., Hartmann, Annette M., Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G., Joshi, Peter K., Kähönen, Mika, Kardia, Sharon L. R., Karlsson, Ida, Kleineidam, Luca, Knopman, David S., Kochan, Nicole A., Konte, Bettina, Kwok, John B., Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Lill, Christina M., Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Jr, Will T., Lopez, Oscar L., Loukola, Anu, Luck, Tobias, Lundervold, Astri J., Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G., Montgomery, Grant W., Murray, Alison D., Need, Anna C., Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A., Psaty, Bruce M., Reppermund, Simone, Riedel-Heller, Steffi G., Rose, Richard J., Rotter, Jerome I., Roussos, Panos, Rovio, Suvi P., Saba, Yasaman, Sabb, Fred W., Sachdev, Perminder S., Satizabal, Claudia L., Schmid, Matthias, Scott, Rodney J., Scult, Matthew A., Simino, Jeannette, Slagboom, P. Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C., Stott, David J., Straub, Richard E., Sundet, Kjetil, Taylor, Adele M., Taylor, Kent D., Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N., Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K. Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab H. H., Arking, Dan E., Bilder, Robert M., Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L., Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L., Gill, Michael, Glahn, David C., Hägg, Sara, Hansell, Narelle K., Hariri, Ahmad R., Ikram, M. Kamran, Jukema, J. Wouter, Vuoksimaa, Eero, Keller, Matthew C., Kremen, William S., Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L., Pendleton, Neil, Porteous, David J., Räikkönen, Katri, Raitakari, Olli T., Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Dan Rujescu, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W., Schofield, Peter R., Starr, John M., Steen, Vidar M., Trollor, Julian N., Turner, Steven T., Van Duijn, Cornelia M., Villringer, Arno, Weinberger, Daniel R., Weir, David R., Wilson, James F., Malhotra, Anil, McIntosh, Andrew M., Gale, Catharine R., Seshadri, Sudha, Mosley, Jr, Thomas H., Bressler, Jan, Lencz, Todd, and Deary, Ian J.

Published
2018
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53. Comparison of the Newborn Infant Parasympathetic Evaluation ( NIPE™ ) index to changes in heart rate to detect intraoperative nociceptive stimuli in healthy and critically ill children below 2 years: An observational study

Author

Neumann, Claudia, primary, Babasiz, Tamara, additional, Straßberger‐Nerschbach, Nadine, additional, Schindler, Ehrenfried, additional, Reuter, Christian, additional, Weinhold, Leonie, additional, Wittmann, Maria, additional, Hilbert, Tobias, additional, and Klaschik, Sven, additional

Published
2022
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54. Erratum to ‘Linking EORTC QLQ-C-30 and PedsQL/PEDQOL physical functioning scores in patients with osteosarcoma’ [Eur J Cancer 170 (2022) 209-235, (S0959804922001629), (10.1016/j.ejca.2022.03.018)]

Author

Budde, Axel, Baust, Katja, Weinhold, Leonie, Bernstein, Mark, Bielack, Stefan, Dhooge, Catharina, Hjorth, Lars, Janeway, Katherine A., Jenney, Meriel, Krailo, Mark D., Marina, Neyssa, Nagarajan, Rajaram, Smeland, Sigbjørn, Sydes, Matthew R., De Vos, Patricia, Whelan, Jeremy, Wiener, Andreas, Calaminus, Gabriele, and Schmid, Matthias

Subjects
Medizin
Abstract

The publisher regrets that errors appear in Table 2a in the printed article. These errors have now been corrected online, and the correct version of Table 2a is given here.[Formula presented] We also note that a Multimedia component was included with the online article in error. This has now been removed from the online article. We can confirm that there are no additional Supplementary Data files to appear with this article. The publisher would like to apologise for any inconvenience caused.

Published
2022

55. Low Serum Vitamin D Status Is Associated with Incident Alzheimer's Dementia in the Oldest Old.

Author

Melo van Lent, Debora, Egert, Sarah, Wolfsgruber, Steffen, Kleineidam, Luca, Weinhold, Leonie, Wagner-Thelen, Holger, Stoffel-Wagner, Birgit, Bickel, Horst, Wiese, Birgitt, Weyerer, Siegfried, Pentzek, Michael, Jessen, Frank, Schmid, Matthias, Maier, Wolfgang, Scherer, Martin, Riedel-Heller, Steffi G., Ramirez, Alfredo, and Wagner, Michael

Abstract

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer's dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies. [ABSTRACT FROM AUTHOR]

Published
2023
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58. ACKT - ein neuer Score zur Vorhersage einer postoperativen invasiven Beatmung nach chirurgischer Behandlung von geriatrischen Meningeompatienten

Author

Scharnböck, Elisa, Weinhold, Leonie, Potthoff, Anna-Laura, Schäfer, Niklas, Heimann, Muriel, Lehmann, Felix, Güresir, Erdem, Bode, Christian, Jacobs, Andreas H., Vatter, Hartmut, Herrlinger, Ulrich, Schneider, Matthias, and Schuss, Patrick

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk-benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Published
2021
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59. Einfluss von Komorbiditäten und Frailty auf frühes Shuntversagen bei geriatrischen Patienten mit Normaldruck-Hydrozephalus

Author

Kilinc, Fatma, Hadjiathanasiou, Alexis, Behmanesh, Bedjan, Güresir, Erdem, Heimann, Muriel, Konczalla, Jürgen, Scharnböck, Elisa, Schneider, Matthias, Weinhold, Leonie, Seifert, Volker, Vatter, Hartmut, Schuss, Patrick, and Gessler, Florian

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Older patients are considered to bear a higher perioperative risk. Since idiopathicnormal pressure hydrocephalus (NPH) predominantly concerns older patients, identifying risk factorsfor early shunt failure for preoperative risk/benefit assessment is indispensable for indication and/orconsultation[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Published
2021

60. Perioperative red blood cell transfusion is associated with poor functional outcome and overall survival in patients with newly diagnosed glioblastoma

Author

Schneider, Matthias, primary, Schäfer, Niklas, additional, Potthoff, Anna-Laura, additional, Weinhold, Leonie, additional, Eichhorn, Lars, additional, Weller, Johannes, additional, Scharnböck, Elisa, additional, Schaub, Christina, additional, Heimann, Muriel, additional, Güresir, Erdem, additional, Lehmann, Felix, additional, Vatter, Hartmut, additional, Herrlinger, Ulrich, additional, and Schuss, Patrick, additional

Published
2021
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61. sj-pdf-1-smm-10.1177_09622802211051088 - Supplemental material for Deselection of base-learners for statistical boosting���with an application to distributional regression

Author

Str��mer, Annika, Staerk, Christian, Klein, Nadja, Weinhold, Leonie, Titze, Stephanie, and Mayr, Andreas

Subjects
111099 Nursing not elsewhere classified, 111708 Health and Community Services, 160807 Sociological Methodology and Research Methods, FOS: Health sciences, FOS: Sociology
Abstract

Supplemental material, sj-pdf-1-smm-10.1177_09622802211051088 for Deselection of base-learners for statistical boosting���with an application to distributional regression by Annika Str��mer, Christian Staerk, Nadja Klein, Leonie Weinhold, Stephanie Titze and Andreas Mayr in Statistical Methods in Medical Research

Published
2021
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66. Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old

Author

Melo van Lent, Debora, primary, Egert, Sarah, additional, Wolfsgruber, Steffen, additional, Kleineidam, Luca, additional, Weinhold, Leonie, additional, Wagner-Thelen, Holger, additional, Maier, Wolfgang, additional, Jessen, Frank, additional, Ramirez, Alfredo, additional, Schmid, Matthias, additional, Scherer, Martin, additional, Riedel-Heller, Steffi G., additional, and Wagner, Michael, additional

Published
2021
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67. PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment

Author

KLEINEIDAM, Luca, Chouraki, Vincent, Próchnicki, Tomasz, van der Lee, Sven, Madrid‑Márquez, Laura, Wagner-Thelen, Holger, Karaca, Ilker, WEINHOLD, Leonie, Wolfsgruber, Steffen, Boland, Anne, Martino Adami, Pamela, Lewczuk, Piotr, POPP, Julius, Brosseron, Frederic, Jansen, Iris, HULSMAN, Marc, Kornhuber, Johannes, Peters, Oliver, Berr, Claudine, Heun, Reinhard, Frölich, Lutz, Tzourio, Christophe, Dartigues, Jean-François, Hüll, Michael, Espinosa, Ana, Hernández, Isabel, de Rojas, Itziar, ORELLANA, Adelina, VALERO, Sergi, STRINGA, Najada, Van Schoor, Natasja, Huisman, Martijn, Scheltens, Philip, For The Alzheimer'S Disease Neuroimaging Initiative, (ADNI), Rüther, Eckart, Deleuze, Jean-François, Wiltfang, Jens, Tarraga, Lluis, Schmid, Matthias, Scherer, Martin, Riedel-Heller, Steffi, Heneka, Michael, Amouyel, Philippe, Jessen, Frank, Boada, Merce, Maier, Wolfgang, Schneider, Anja, González‑Pérez, Antonio, van der Flier, Wiesje, Wagner, Michael, Lambert, Jean-Charles, Holstege, Henne, Saez, Mª Eugenia, Latz, Eicke, Ruiz, Agustin, Ramirez, Alfredo, University Hospital Bonn, Universität zu Köln, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Amsterdam UMC, Vrije Universiteit Amsterdam [Amsterdam] (VU), Centro andaluz de estudios bioinformáticos - Andalusian Bioinformatics Research Centre [Sevilla] (CAEBi), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universitätsklinikum Erlangen [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of Bialystok, Lausanne University Hospital, University hospital of Zurich [Zurich], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Universität Heidelberg [Heidelberg], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert-Ludwigs-Universität Freiburg, Universitat Internacional de Catalunya [Barcelona] (UIC), Instituto de Salud Carlos III [Madrid] (ISC), University Medical Center Göttingen (UMG), Universidade de Aveiro, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Universität Leipzig [Leipzig], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Open Access funding provided by Projekt DEAL. This publication was funded in part by the German Federal Ministry of Education and Research (BMBF) (grants KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434, grants KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B). Analyses were also funded by the German Federal Ministry of Education and Research (BMBF 01EA1410A) within the project 'Diet-Body-Brain: from epidemiology to evidence-based communication'. Part of the work was funded by the JPND EADB grant (German Federal Ministry of Education and Research (BMBF) grant: 01ED1619A). Part of the analysis was funded by the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. 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). Data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Araclon Biotech, BioClinica, Inc., Biogen, Bristol-Myers Squibb Company, CereSpir, Inc., Cogstate, Eisai Inc., ElanPharmaceuticals, Inc., Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc., Fujirebio, GE Healthcare, IXICO Ltd., Janssen Alzheimer Immunotherapy Research and Development, LLC., Johnson and Johnson Pharmaceutical Research and Development LLC., Lumosity, Lundbeck, Merck and Co., Inc., Meso Scale Diagnostics, LLC., NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer Inc., Piramal Imaging, Servier, Takeda Pharmaceutical Company, and transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of Southern California. The Three-City Study genotyping and analysis was funded by the GENMED Labex, the Joint Programming Initiative on Neurodegenerative Diseases Research (JPND, PERADES project), the Institute Pasteur de Lille, the University of Lille, and the Nord-Pas de Calais Regional Council. This work also benefited from the Lille Métropole Communauté Urbaine Council, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease). In addition, the Three-City Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. Additional funding for the 3C Study was also obtained from the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM 'Cohortes et collections de données biologiques' programme. Lille Génopôle received an unconditional grant from Eisai. Fundacio ACE cohort receives support from the Innovative Medicines Initiative 2 Joint Undertaking which receives support from the European Union’s Horizon 2020 research and innovation programme (ADAPTED Grant No. 115975). A. Ruiz’s research is also supported by Instituto de Salud Carlos III (ISCIII) grants PI13/02434, PI16/01861, and PI19/01301. Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-'Una manera de Hacer Europa'), by Fundación bancaria 'La Caixa' and Grifols SA (GR@ACE project). For the Longitudinal Aging Study Amsterdam (LASA) supports was largely obtained from a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The data collection in 2012–2013 was financially supported by the Netherlands Organization for Scientific Research (NWO) in the framework of the project 'New Cohorts of young old in the twenty-first century' (File Number 480-10-014). Genotyping using Axiom-NL array was financially supported by EMGO+ Research Institute. PL was supported by the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. JW is supported by an Ilídio Pinho professorship and iBiMED (UID/BIM/04501/2013), at the University of Aveiro, Portugal. JP was supported by a grant from the Swiss National Science Foundation (320030L_141179)., Universität zu Köln = University of Cologne, Amsterdam UMC - Amsterdam University Medical Center, Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Leipzig, Alzheimer's Disease Neuroimaging Initiative (ADNI), Kleineidam, L., Karaca, I., Heneka, M.T., Maier, W., Schneider, A., Wagner, M., Chouraki, V., Amouyel, P., Lambert, J.C., Próchnicki, T., Latz, E., van der Lee, S.J., Jansen, I.E., Hulsman, M., Scheltens, P., van der Flier, W.M., Holstege, H., Madrid-Márquez, L., González-Pérez, A., Sáez, M.E., Wagner-Thelen, H., Martino Adami, P.V., Jessen, F., Ramirez, A., Weinhold, L., Schmid, M., Wolfsgruber, S., Brosseron, F., Boland, A., Deleuze, J.F., Lewczuk, P., Kornhuber, J., Popp, J., Peters, O., Berr, C., Heun, R., Frölich, L., Tzourio, C., Dartigues, J.F., Hüll, M., Espinosa, A., Hernández, I., de Rojas, I., Orellana, A., Valero, S., Ruiz, A., Tarraga, L., Boada, M., Stringa, N., van Schoor, N.M., Huisman, M., Rüther, E., Wiltfang, J., Scherer, M., Riedel-Heller, S., Neurology, Human genetics, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Amsterdam Neuroscience - Complex Trait Genetics, APH - Personalized Medicine, APH - Methodology, Sociology, and The Social Context of Aging (SoCA)

Subjects
Apolipoprotein E, Male, pathology [Cognitive Dysfunction], Cognitive decline, genetics [Alzheimer Disease], Disease, SEPIA, pathology [Alzheimer Disease], 0302 clinical medicine, Cognition, genetics [Amyloid beta-Peptides], Medicine, Aged, 80 and over, 0303 health sciences, education.field_of_study, Microglia, physiology [Cognition], Middle Aged, medicine.anatomical_structure, Disease Progression, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], analysis [Biomarkers], Alzheimer’s disease, Amyloid, Phospholipase C gamma 2, Population, tau Proteins, Pathology and Forensic Medicine, PLCG2, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Alzheimer Disease, Humans, Cognitive Dysfunction, ddc:610, education, Mild cognitive impairment, HEALTHY, 030304 developmental biology, Aged, metabolism [Phospholipase C gamma], Original Paper, Amyloid beta-Peptides, TREM2, business.industry, Phospholipase C gamma, genetics [Cognitive Dysfunction], metabolism [tau Proteins], cerebrospinal fluid [tau Proteins], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Immunology, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
Abstract

A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer’s disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau181, total tau, and Aβ1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau181 levels in CSF. The effect size of the association of p.P522R with the cognitive decline and pTau181 was similar to that of APOE-ε4, the strongest genetic risk factor for AD. Interestingly, the protective effect of p.P522R was more pronounced in MCI patients with low Aβ1-42 levels suggesting a role of PLCG2 in the response to amyloid pathology. In line with this hypothesis, we observed no protective effect of the PLCG2 variant on the cognitive decline in population-based studies probably due to the lower prevalence of amyloid positivity in these samples compared to MCI patients. Concerning the potential biological underpinnings, we identified a network of co-expressed proteins connecting PLCG2 to APOE and TREM2 using unsupervised co-regulatory network analysis. The network was highly enriched for the complement cascade and genes differentially expressed in disease-associated microglia. Our data show that p.P522R in PLCG2 reduces AD disease progression by mitigating tau pathology in the presence of amyloid pathology and, as a consequence, maintains cognitive function. Targeting the enzyme PLCG2 might provide a new therapeutic approach for treating AD.

Published
2020

68. ACKT: A Proposal for a Novel Score to Predict Prolonged Mechanical Ventilation after Surgical Treatment of Meningioma in Geriatric Patients

Author

Scharnböck, Elisa, primary, Weinhold, Leonie, additional, Potthoff, Anna-Laura, additional, Schäfer, Niklas, additional, Heimann, Muriel, additional, Lehmann, Felix, additional, Güresir, Erdem, additional, Bode, Christian, additional, Jacobs, Andreas H., additional, Vatter, Hartmut, additional, Herrlinger, Ulrich, additional, Schneider, Matthias, additional, and Schuss, Patrick, additional

Published
2020
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69. Impact of Comorbidities and Frailty on Early Shunt Failure in Geriatric Patients With Normal Pressure Hydrocephalus

Author

Hadjiathanasiou, Alexis, primary, Kilinc, Fatma, additional, Behmanesh, Bedjan, additional, Bernstock, Joshua, additional, Güresir, Erdem, additional, Heimann, Muriel, additional, Konczalla, Jürgen, additional, Scharnböck, Elisa, additional, Schneider, Matthias, additional, Weinhold, Leonie, additional, Seifert, Volker, additional, Vatter, Hartmut, additional, Gessler, Florian, additional, and Schuss, Patrick, additional

Published
2020
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71. Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases

Author

Schneider, Matthias, primary, Heimann, Muriel, additional, Schaub, Christina, additional, Eichhorn, Lars, additional, Potthoff, Anna-Laura, additional, Giordano, Frank A., additional, Güresir, Erdem, additional, Ko, Yon-Dschun, additional, Landsberg, Jennifer, additional, Lehmann, Felix, additional, Radbruch, Alexander, additional, Schwab, Katjana S., additional, Weinhold, Leonie, additional, Weller, Johannes, additional, Wispel, Christian, additional, Herrlinger, Ulrich, additional, Vatter, Hartmut, additional, Schäfer, Niklas, additional, and Schuss, Patrick, additional

Published
2020
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75. M62 THE POLYGENIC RISK FOR OBSESSIVE-COMPULSIVE DISORDER IS ASSOCIATED WITH HARM AVOIDANCE IN A SAMPLE OF OCD PATIENTS, UNAFFECTED RELATIVES AND CONTROLS

Author

Bey, Katharina, primary, Weinhold, Leonie, additional, Grützmann, Rosa, additional, Heinzel, Stephan, additional, Kaufmann, Christian, additional, Klawohn, Julia, additional, Riesel, Anja, additional, Lennertz, Leonhard, additional, Schmid, Matthias, additional, Ramirez, Alfredo, additional, Kathmann, Norbert, additional, and Wagner, Michael, additional

Published
2019
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76. Vergleich des Outcome von Arthrodese und Revisionsendoprothese nach fehlgeschlagener Kniegelenksendoprothese bei periprothetischer Infektion

Author

Gathen, Martin, Gravius, Sascha, Randau, Thomas, Wimmer, Matthias D., Weinhold, Leonie, Plöger, Milena, and Friedrich, Max

Subjects
Arthrodese, Revisionsendoprothese, ddc: 610, 610 Medical sciences, Medicine, Periprothetische Infektion
Abstract

Fragestellung: Die periprothetische Infektion des Kniegelenkes eine der schwerwiegende Komplikationen nach Kniegelenkersatz. Ausgeprägte Knochen- und Weichteildestruktionen, insbesondere der Zustand des Streckapparates, können die erneute Implantation einer Revisionsprothese unmöglich[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2018)

Published
2018

77. Drug-related problems in head and neck cancer patients identified by repeated medication reviews on consecutive therapy cycles.

Author

Vucur, Corinna, Wirtz, Daniel A, Weinhold, Leonie, Zipfel, Matthias, Schmid, Matthias, Schmidt-Wolf, Ingo GH, and Jaehde, Ulrich

Subjects
HEAD tumors, EXPERIMENTAL design, SCIENTIFIC observation, TREATMENT duration, CANCER patients, CHEMORADIOTHERAPY, MEDICATION therapy management, INAPPROPRIATE prescribing (Medicine), DRUGS, MEDICAL history taking, DESCRIPTIVE statistics, DRUG interactions, QUALITY of life, DRUG side effects, NECK tumors, DRUG toxicity
Abstract

Background: Head and neck cancer (HNC) patients are particularly vulnerable to drug-related problems (DRPs) given the toxicity of concomitant chemoradiotherapy (CCRT). Objective: To investigate the number and type of potential DRPs (pDRPs) in HNC outpatients undergoing five consecutive cycles of CCRT. Methods: A single-centre, non-randomized, non-interventional, observational study was conducted at the Oncological Outpatient Clinic of the Center for Integrated Oncology at the University Hospital Bonn, Germany. Clinical pharmacists took a comprehensive medication history, documented laboratory data, assessed patients' symptom burden, and retrospectively performed medication reviews at study entry and on the first day of each therapy cycle without any clinical intervention. Results: In 26 patients, the mean number of pDRPs continuously increased during therapy course, from 4.8 (SD 2.7, range 2–12) at cycle 1 to 6.9 (SD 2.6, range 2–12) at cycle 5, with drug-drug interactions, adverse drug reactions, inappropriate durations of use, and inappropriate dosage intervals being the most common. Considering only new and recurrent pDRPs, the mean number was 4.3 (SD 2.3, range 2–9) at cycle 1 and lower in the further therapy course with an average of 1.3 (SD 1.7, range 0–7) at cycle 2 and 1.9 (SD 1.5, range 0–5) at cycle 5. The number of pDRPs was found to be associated with medication regimen complexity and health-related quality of life assessed in the first therapy cycle. Conclusion: pDRPs frequently occurred in HNC outpatients demonstrating the need for pharmaceutical care. A methodological framework for repeated medication reviews was established, facilitating implementation into routine healthcare practice. [ABSTRACT FROM AUTHOR]

Published
2021
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79. Longitudinal Course of Short-Term Variation and Doppler Parameters in Early Onset Growth Restricted Fetuses

Author

Baier, Friederike, additional, Weinhold, Leonie, additional, Stumpfe, Florian M., additional, Kehl, Sven, additional, Pretscher, Jutta, additional, Bayer, Christian M., additional, Topal, Nalan, additional, Pontones, Constanza, additional, Mayr, Andreas, additional, Schild, Ralf, additional, Schmid, Matthias, additional, Beckmann, Matthias W., additional, and Faschingbauer, Florian, additional

Published
2019
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80. Health status, health-related quality of life, and socioeconomic outcome in childhood brain tumor survivors: a German cohort study

Author

Scholtes, Cathy, primary, Baust, Katja, additional, Weinhold, Leonie, additional, Creutzig, Ursula, additional, Gnekow, Astrid, additional, Hinz, Andreas, additional, Kaatsch, Peter, additional, Kreitz, Kiana, additional, Langer, Thorsten, additional, Rutkowski, Stefan, additional, Singer, Susanne, additional, Spix, Claudia, additional, Teske, Carmen, additional, Schmid, Matthias, additional, Dilloo, Dagmar, additional, and Calaminus, Gabriele, additional

Published
2019
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85. P3‐122: APOE ‐ε4 MODULATES LEVELS OF OMEGA‐3 AND OMEGA‐6 FATTY ACIDS IN ALZHEIMER'S DISEASE DEMENTIA

Author

Wagner-Thelen, Holger, primary, Weinhold, Leonie, additional, Leber, Markus, additional, Kawalia, Amit, additional, Kleineidam, Luca, additional, Böhmer, Anne C., additional, Heilman, Stefanie, additional, Schmid, Matthias, additional, Wagner, Michael, additional, Riedel-Heller, Steffi G., additional, Luck, Tobias, additional, Egert, Sarah, additional, Jessen, Frank, additional, Maier, Wolfgang, additional, and Ramirez, Alfredo, additional

Published
2018
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86. Prospective Associations between Single Foods, Alzheimer’s Dementia and Memory Decline in the Elderly

Author

Fischer, Karina, primary, Melo van Lent, Debora, additional, Wolfsgruber, Steffen, additional, Weinhold, Leonie, additional, Kleineidam, Luca, additional, Bickel, Horst, additional, Scherer, Martin, additional, Eisele, Marion, additional, van den Bussche, Hendrik, additional, Wiese, Birgitt, additional, König, Hans-Helmut, additional, Weyerer, Siegfried, additional, Pentzek, Michael, additional, Röhr, Susanne, additional, Maier, Wolfgang, additional, Jessen, Frank, additional, Schmid, Matthias, additional, Riedel-Heller, Steffi, additional, and Wagner, Michael, additional

Published
2018
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88. PLCG2 Protective Variant p.P522R Modulates Tau Pathology and Disease Progression in Patients with Mild Cognitive Impairment

Author

Kleineidam, Luca, primary, Chouraki, Vincent, additional, Próchnicki, Thomas, additional, van der Lee, Sven, additional, Madrid-Márquez, Laura, additional, Wagner-Thelen, Holger, additional, Karaca, Ilker, additional, Weinhold, Leonie, additional, Wolfsgruber, Steffen, additional, Boland, Anne, additional, Martino Adami, Pamela V., additional, Lewczuk, Piotr, additional, Popp, Julius, additional, Brosseron, Frederic, additional, Jansen, Iris, additional, Hulsman, Marc, additional, Kornhuber, Johannes, additional, Peters, Oliver, additional, Berr, Claudine, additional, Heun, Reinhard, additional, Frölich, Lutz, additional, Tzourio, Christopher, additional, Dartigues, Jean-François, additional, Espinosa, Ana, additional, Hernandez, Isabel, additional, de Rojas, Itziar, additional, Orellana, Adela, additional, Valero, Sergi, additional, Stringa, Najada, additional, van Schoor, Natasja M., additional, Huisman, Martijn A., additional, Scheltens, Philip, additional, Deleuze, Jean-Francois, additional, Wiltfang, Jens, additional, Tarraga, Lluis, additional, Schmid, Matthias, additional, Scherer, Martin, additional, Riedel-Heller, Steffi, additional, Heneka, Michael T., additional, Amouyel, Philippe, additional, Jessen, Frank, additional, Boada, Merce, additional, Maier, Wolfgang, additional, Schneider, Anja, additional, González-Pérez, Antonio, additional, van der Flier, Wiesje M., additional, Wagner, Michael, additional, Lambert, Jean-Charles, additional, Holstege, Henne, additional, Sáez, Mª Eugenia, additional, Latz, Eicke, additional, Ruiz, Agustin, additional, and Ramirez, Alfredo, additional

Published
2018
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89. Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)

Author

Davies, Gail, primary, Lam, Max, additional, Harris, Sarah E, additional, Trampush, Joey W, additional, Luciano, Michelle, additional, Hill, W David, additional, Hagenaars, Saskia P, additional, Ritchie, Stuart J, additional, Marioni, Riccardo E, additional, Fawns-Ritchie, Chloe, additional, Liewald, David CM, additional, Okely, Judith A, additional, Ahola-Olli, Ari V, additional, Barnes, Catriona LK, additional, Bertram, Lars, additional, Bis, Joshua C, additional, Burdick, Katherine E, additional, Christoforou, Andrea, additional, DeRosse, Pamela, additional, Djurovic, Srdjan, additional, Espeseth, Thomas, additional, Giakoumaki, Stella, additional, Giddaluru, Sudheer, additional, Gustavson, Daniel E, additional, Hayward, Caroline, additional, Hofer, Edith, additional, Ikram, M Arfan, additional, Karlsson, Robert, additional, Knowles, Emma, additional, Lahti, Jari, additional, Leber, Markus, additional, Li, Shuo, additional, Mather, Karen A, additional, Melle, Ingrid, additional, Morris, Derek, additional, Oldmeadow, Christopher, additional, Palviainen, Teemu, additional, Payton, Antony, additional, Pazoki, Raha, additional, Petrovic, Katja, additional, Reynolds, Chandra A, additional, Sargurupremraj, Muralidharan, additional, Scholz, Markus, additional, Smith, Jennifer A, additional, Smith, Albert V, additional, Terzikhan, Natalie, additional, Thalamuthu, Anbu, additional, Trompet, Stella, additional, Lee, Sven J van der, additional, Ware, Erin B, additional, Windham, B Gwen, additional, Wright, Margaret J, additional, Yang, Jingyun, additional, Yu, Jin, additional, Ames, David, additional, Amin, Najaf, additional, Amouyel, Philippe, additional, Andreassen, Ole A, additional, Armstrong, Nicola J, additional, Assareh, Amelia A, additional, Attia, John R, additional, Attix, Deborah, additional, Avramopoulos, Dimitrios, additional, Bennett, David A, additional, Böhmer, Anne C, additional, Boyle, Patricia A, additional, Brodaty, Henry, additional, Campbell, Harry, additional, Cannon, Tyrone D, additional, Cirulli, Elizabeth T, additional, Congdon, Eliza, additional, Conley, Emily Drabant, additional, Corley, Janie, additional, Cox, Simon R, additional, Dale, Anders M, additional, Dehghan, Abbas, additional, Dick, Danielle, additional, Dickinson, Dwight, additional, Eriksson, Johan G, additional, Evangelou, Evangelos, additional, Faul, Jessica D, additional, Ford, Ian, additional, Freimer, Nelson A, additional, Gao, He, additional, Giegling, Ina, additional, Gillespie, Nathan A, additional, Gordon, Scott D, additional, Gottesman, Rebecca F, additional, Griswold, Michael E, additional, Gudnason, Vilmundur, additional, Harris, Tamara B, additional, Hartmann, Annette M, additional, Hatzimanolis, Alex, additional, Heiss, Gerardo, additional, Holliday, Elizabeth G, additional, Joshi, Peter K, additional, Kähönen, Mika, additional, Kardia, Sharon LR, additional, Karlsson, Ida, additional, Kleineidam, Luca, additional, Knopman, David S, additional, Kochan, Nicole A, additional, Konte, Bettina, additional, Kwok, John B, additional, Hellard, Stephanie Le, additional, Lee, Teresa, additional, Lehtimäki, Terho, additional, Li, Shu-Chen, additional, Liu, Tian, additional, Koini, Marisa, additional, London, Edythe, additional, Longstreth, Will T, additional, Lopez, Oscar L, additional, Loukola, Anu, additional, Luck, Tobias, additional, Lundervold, Astri J, additional, Lundquist, Anders, additional, Lyytikäinen, Leo-Pekka, additional, Martin, Nicholas G, additional, Montgomery, Grant W, additional, Murray, Alison D, additional, Need, Anna C, additional, Noordam, Raymond, additional, Nyberg, Lars, additional, Ollier, William, additional, Papenberg, Goran, additional, Pattie, Alison, additional, Polasek, Ozren, additional, Poldrack, Russell A, additional, Psaty, Bruce M, additional, Reppermund, Simone, additional, Riedel-Heller, Steffi G, additional, Rose, Richard J, additional, Rotter, Jerome I, additional, Roussos, Panos, additional, Rovio, Suvi P, additional, Saba, Yasaman, additional, Sabb, Fred W, additional, Sachdev, Perminder S, additional, Satizabal, Claudia, additional, Schmid, Matthias, additional, Scott, Rodney J, additional, Scult, Matthew A, additional, Simino, Jeannette, additional, Slagboom, P Eline, additional, Smyrnis, Nikolaos, additional, Soumaré, Aïcha, additional, Stefanis, Nikos C, additional, Stott, David J, additional, Straub, Richard E, additional, Sundet, Kjetil, additional, Taylor, Adele M, additional, Taylor, Kent D, additional, Tzoulaki, Ioanna, additional, Tzourio, Christophe, additional, Uitterlinden, André, additional, Vitart, Veronique, additional, Voineskos, Aristotle N, additional, Kaprio, Jaakko, additional, Wagner, Michael, additional, Wagner, Holger, additional, Weinhold, Leonie, additional, Wen, K Hoyan, additional, Widen, Elisabeth, additional, Yang, Qiong, additional, Zhao, Wei, additional, Adams, Hieab HH, additional, Arking, Dan E, additional, Bilder, Robert M, additional, Bitsios, Panos, additional, Boerwinkle, Eric, additional, Chiba-Falek, Ornit, additional, Corvin, Aiden, additional, Jager, Philip L De, additional, Debette, Stéphanie, additional, Donohoe, Gary, additional, Elliott, Paul, additional, Fitzpatrick, Annette L, additional, Gill, Michael, additional, Glahn, David C, additional, Hägg, Sara, additional, Hansell, Narelle K, additional, Hariri, Ahmad R, additional, Ikram, M Kamran, additional, Jukema, J. Wouter, additional, Vuoksimaa, Eero, additional, Keller, Matthew C, additional, Kremen, William S, additional, Launer, Lenore, additional, Lindenberger, Ulman, additional, Palotie, Aarno, additional, Pedersen, Nancy L, additional, Pendleton, Neil, additional, Porteous, David J, additional, Räikkönen, Katri, additional, Raitakari, Olli T, additional, Ramirez, Alfredo, additional, Reinvang, Ivar, additional, Rudan, Igor, additional, Rujescu, Dan, additional, Schmidt, Reinhold, additional, Schmidt, Helena, additional, Schofield, Peter W, additional, Schofield, Peter R, additional, Starr, John M, additional, Steen, Vidar M, additional, Trollor, Julian N, additional, Turner, Steven T, additional, Duijn, Cornelia M Van, additional, Villringer, Arno, additional, Weinberger, Daniel R, additional, Weir, David R, additional, Wilson, James F, additional, Malhotra, Anil, additional, McIntosh, Andrew M, additional, Gale, Catharine R, additional, Seshadri, Sudha, additional, Mosley, Thomas H., additional, Bressler, Jan, additional, Lencz, Todd, additional, and Deary, Ian J, additional

Published
2017
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92. The betaboost package—a software tool for modelling bounded outcome variables in potentially high-dimensional epidemiological data.

Author

Mayr, Andreas, Weinhold, Leonie, Hofner, Benjamin, Titze, Stephanie, Gefeller, Olaf, and Schmid, Matthias

Subjects
*REGRESSION analysis, *STATISTICAL software, *STATISTICAL learning, *EPIDEMIOLOGY, *COMPUTER software
Abstract

Motivation To provide an integrated software environment for model fitting and variable selection in regression models with a bounded outcome variable. Implementation The proposed modelling framework is implemented in the add-on package betaboost of the statistical software environment R. General features The betaboost methodology is based on beta-regression, which is a state-of-the-art method for modelling bounded outcome variables. By combining traditional model fitting techniques with recent advances in statistical learning and distributional regression, betaboost allows users to carry out data-driven variable and/or confounder selection in potentially high-dimensional epidemiological data. The software package implements a flexible routine to incorporate linear and non-linear predictor effects in both the mean and the precision parameter (relating inversely to the variance) of a beta-regression model. Availability The software is hosted publicly at [ http://github.com/boost-R/betaboost ] and has been published under General Public License (GPL) version 3 or newer. [ABSTRACT FROM AUTHOR]

Published
2018
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95. ACKT: A Proposal for a Novel Score to Predict Prolonged Mechanical Ventilation after Surgical Treatment of Meningioma in Geriatric Patients.

Author

Scharnböck, Elisa, Weinhold, Leonie, Potthoff, Anna-Laura, Schäfer, Niklas, Heimann, Muriel, Lehmann, Felix, Güresir, Erdem, Bode, Christian, Jacobs, Andreas H., Vatter, Hartmut, Herrlinger, Ulrich, Schneider, Matthias, and Schuss, Patrick

Subjects
*C-reactive protein, *CONFIDENCE intervals, *MANN Whitney U Test, *ARTIFICIAL respiration, *RISK assessment, *MENINGIOMA, *DESCRIPTIVE statistics, *LOGISTIC regression analysis, *OLD age
Abstract

Simple Summary: Meningiomas are most commonly benign intracranial tumors, and surgical resection represents the treatment modality of choice. However, especially for patients of higher age and with increasing comorbidities, brain surgery might be accompanied by the need for postoperative prolonged intensive care, which might impair intended operative benefit. In the present study, we therefore analyzed prolonged mechanical ventilation (PMV) as an indicator variable for such intensive care treatment with regard to potential effects on mortality after meningioma resection in patients aged 70 years and older. We found that patients with postoperative PMV exhibited a profoundly increased probability to die within 1 year after surgery. Based on these findings, we identified risk factors for postoperative PMV occurrence and developed an easy-to-use score which allows us to estimate the risk of PMV occurrence preliminary to the surgical resection. We believe that this score might help to more sufficiently guide patients in the course of risk–benefit assessment and preoperative counseling. Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk–benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients with meningioma. We therefore analyzed the impact of PMV on mortality in geriatric patients who had undergone meningioma resection. Between 2009 and 2019, 261 patients aged ≥ 70 years were surgically treated for intracranial meningioma at our institution. PMV was defined as postoperative invasive ventilation of >7 days. Postoperative PMV was present in 17 of 261 geriatric meningioma patients (7%). Twenty-five geriatric patients (10%) died within 1 year after surgery. A scoring system ("ACKT") based on the variables of age, preoperative C-reactive protein (CRP) value, Karnofsky performance scale and tumor size supports prediction of postoperative PMV (sensitivity 73%, specificity 84%). PMV is significantly associated with increased mortality after surgical treatment of meningiomas in geriatric patients. Furthermore, we suggest a novel score ("ACKT") to preoperatively estimate the risk of PMV occurrence, which might help to guide future risk–benefit assessment and patient counseling in the geriatric meningioma population. [ABSTRACT FROM AUTHOR]

Published
2021
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96. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Author

De Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, De Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar AL, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, Van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande AL, EADB Contributors, GR@ACE Study Group, DEGESCO Consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ Consortia, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez De Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, Van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, Van Der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, Van Der Lee, Sven J, and Ruiz, Agustín

Subjects
Aged, 80 and over, Male, Heterozygote, Multifactorial Inheritance, Datasets as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, 3. Good health, Cohort Studies, Amyloid beta-Protein Precursor, Apolipoproteins E, Alzheimer Disease, Risk Factors, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, Age of Onset, Aged, Follow-Up Studies, Genome-Wide Association Study
Abstract

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061, 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.

97. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Davies, Gail, Lam, Max, Harris, Sarah E, Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P, Ritchie, Stuart J, Marioni, Riccardo E, Fawns-Ritchie, Chloe, Liewald, David CM, Okely, Judith A, Ahola-Olli, Ari V, Barnes, Catriona LK, Bertram, Lars, Bis, Joshua C, Burdick, Katherine E, Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E, Hayward, Caroline, Hofer, Edith, Ikram, M Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Li, Shuo, Mather, Karen A, Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A, Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A, Smith, Albert V, Terzikhan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella, Van Der Lee, Sven J, Ware, Erin B, Windham, B Gwen, Wright, Margaret J, Yang, Jingyun, Yu, Jin, Ames, David, Amin, Najaf, Amouyel, Philippe, Andreassen, Ole A, Armstrong, Nicola J, Assareh, Amelia A, Attia, John R, Attix, Deborah, Avramopoulos, Dimitrios, Bennett, David A, Böhmer, Anne C, Boyle, Patricia A, Brodaty, Henry, Campbell, Harry, Cannon, Tyrone D, Cirulli, Elizabeth T, Congdon, Eliza, Conley, Emily Drabant, Corley, Janie, Cox, Simon R, Dale, Anders M, Dehghan, Abbas, Dick, Danielle, Dickinson, Dwight, Eriksson, Johan G, Evangelou, Evangelos, Faul, Jessica D, Ford, Ian, Freimer, Nelson A, Gao, He, Giegling, Ina, Gillespie, Nathan A, Gordon, Scott D, Gottesman, Rebecca F, Griswold, Michael E, Gudnason, Vilmundur, Harris, Tamara B, Hartmann, Annette M, Hatzimanolis, Alex, Heiss, Gerardo, Holliday, Elizabeth G, Joshi, Peter K, Kähönen, Mika, Kardia, Sharon LR, Karlsson, Ida, Kleineidam, Luca, Knopman, David S, Kochan, Nicole A, Konte, Bettina, Kwok, John B, Le Hellard, Stephanie, Lee, Teresa, Lehtimäki, Terho, Li, Shu-Chen, Liu, Tian, Koini, Marisa, London, Edythe, Longstreth, Will T, Lopez, Oscar L, Loukola, Anu, Luck, Tobias, Lundervold, Astri J, Lundquist, Anders, Lyytikäinen, Leo-Pekka, Martin, Nicholas G, Montgomery, Grant W, Murray, Alison D, Need, Anna C, Noordam, Raymond, Nyberg, Lars, Ollier, William, Papenberg, Goran, Pattie, Alison, Polasek, Ozren, Poldrack, Russell A, Psaty, Bruce M, Reppermund, Simone, Riedel-Heller, Steffi G, Rose, Richard J, Rotter, Jerome I, Roussos, Panos, Rovio, Suvi P, Saba, Yasaman, Sabb, Fred W, Sachdev, Perminder S, Satizabal, Claudia L, Schmid, Matthias, Scott, Rodney J, Scult, Matthew A, Simino, Jeannette, Slagboom, P Eline, Smyrnis, Nikolaos, Soumaré, Aïcha, Stefanis, Nikos C, Stott, David J, Straub, Richard E, Sundet, Kjetil, Taylor, Adele M, Taylor, Kent D, Tzoulaki, Ioanna, Tzourio, Christophe, Uitterlinden, André, Vitart, Veronique, Voineskos, Aristotle N, Kaprio, Jaakko, Wagner, Michael, Wagner, Holger, Weinhold, Leonie, Wen, K Hoyan, Widen, Elisabeth, Yang, Qiong, Zhao, Wei, Adams, Hieab HH, Arking, Dan E, Bilder, Robert M, Bitsios, Panos, Boerwinkle, Eric, Chiba-Falek, Ornit, Corvin, Aiden, De Jager, Philip L, Debette, Stéphanie, Donohoe, Gary, Elliott, Paul, Fitzpatrick, Annette L, Gill, Michael, Glahn, David C, Hägg, Sara, Hansell, Narelle K, Hariri, Ahmad R, Ikram, M Kamran, Jukema, J Wouter, Vuoksimaa, Eero, Keller, Matthew C, Kremen, William S, Launer, Lenore, Lindenberger, Ulman, Palotie, Aarno, Pedersen, Nancy L, Pendleton, Neil, Porteous, David J, Räikkönen, Katri, Raitakari, Olli T, Ramirez, Alfredo, Reinvang, Ivar, Rudan, Igor, Rujescu, Dan, Schmidt, Reinhold, Schmidt, Helena, Schofield, Peter W, Schofield, Peter R, Starr, John M, Steen, Vidar M, Trollor, Julian N, Turner, Steven T, Van Duijn, Cornelia M, Villringer, Arno, Weinberger, Daniel R, Weir, David R, Wilson, James F, Malhotra, Anil, McIntosh, Andrew M, Gale, Catharine R, Seshadri, Sudha, Mosley, Thomas H, Bressler, Jan, Lencz, Todd, and Deary, Ian J

Subjects
quantitative trait, cognitive neuroscience, genetics of the nervous system, genome-wide association studies, 3. Good health
Abstract

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

98. New insights on the genetic etiology of Alzheimer’s and related dementia

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris, Andrade, Victor, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C., Grenier-Boley, Benjamin, Campos-Martin, Rafael, Holmans, Peter A., Boland, Anne, Kleineidam, Luca, Damotte, Vincent, van der Lee, Sven J., Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C., Yaqub, Amber, Prokic, Ivana, Costa, Marcos R, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Boada, Mercè, Aarsland, Dag, García-González, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J., Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Belén Pastor, Ana, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizzarro, Alessandra, Alcolea, Daniel, Blesa, Rafael, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bresner, Catherine, Brookes, Keeley J., Brusco, Luis Ignacio, Bûrger, Katharina, Bullido, María J., Burholt, Vanessa, Bush, William S., Calero, Miguel, Dufouil, Carole, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chillotti, Caterina, Brodaty, Henry, Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D., Debette, Stéphanie, Deckert, Jürgen, del Ser, Teodoro, Denning, Nicola, DeStefano, Anita, Dichgans, Martin, Diehl-Schmid, Janine, Diez-Fairen, Mónica, Rossi, Paolo Dionigi, Djurovic, Srdjan, Duron, Emmanuelle, Düzel, Emrah, Engelborghs, Sebastiaan, Escott-Price, Valentina, Espinosa, Ana, Buiza-Rueda, Dolores, Ewers, Michael, Tagliavini, Fabrizio, Nielsen, Sune Fallgaard, Farotti, Lucia, Fenoglio, Chiara, Fernández-Fuertes, Marta, Hardy, John, Ferrari, Raffaele, Ferreira, Catarina B, Ferri, Evelyn, Fin, Bertrand, Fischer, Peter, Fladby, Tormod, Fließbach, Klaus, Fortea, Juan, Fostinelli, Silvia, Fox, Nick C., Franco-Macías, Emlio, Frank-García, Ana, Froelich, Lutz, Galimberti, Daniela, García-Alberca, Jose Maria, Garcia-Madrona, Sebastian, García-Ribas, Guillermo, Chene, Geneviève, Ghidoni, Roberta, Giegling, Ina, Giaccone, Giorgio, Goldhardt, Oliver, González-Pérez, Antonio, Graff, Caroline, Grande, Giulia, Green, Emma, Grimmer, Timo, Grünblatt, Edna, Guetta-Baranes, Tamar, Haapasalo, Annakaisa, Hadjigeorgiou, Georgios, Haines, Jonathan L., Hamilton-Nelson, Kara L., Hampel, Harald, Hanon, Olivier, Hartmann, Annette M., Hausner, Lucrezia, Harwood, Janet, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herrmann, Martin J., Hoffmann, Per, Holmes, Clive, Holstege, Henne, Vilas, Raquel Huerto, Hulsman, Marc, Humphrey, Jack, Biessels, Geert Jan, Johansson, Charlotte, Kehoe, Patrick G., Kilander, Lena, Ståhlbom, Anne Kinhult, Kivipelto, Miia, Koivisto, Anne, Kornhuber, Johannes, Kosmidis, Mary H., Kuksa, Pavel P., Kunkle, Brian W., Lage, Carmen, Laukka, Erika J, Lauria, Alessandra, Lee, Chien-Yueh, Lehtisalo, Jenni, Satizabal, Claudia L., Lerch, Ondrej, Lleó, Alberto, Lopez, Rogelio, Lopez, Oscar, de Munain, Adolfo Lopez, Love, Seth, Löwemark, Malin, Luckcuck, Lauren, Macías, Juan, MacLeod, Catherine A., Maier, Wolfgang, Mangialasche, Francesca, Spallazzi, Marco, Marquié, Marta, Marshall, Rachel, Martin, Eden R., Martín Montes, Angel, Rodríguez, Carmen Martínez, Masullo, Carlo, Mayeux, Richard, Mead, Simon, Mecocci, Patrizia, Medina, Miguel, Meggy, Alun, Mendoza, Silvia, Menéndez-González, Manuel, Mir, Pablo, Periñán, Maria Teresa, Mol, Merel, Molina-Porcel, Laura, Montrreal, Laura, Morelli, Laura, Moreno, Fermín, Morgan, Kevin, Nöthen, Markus M., Muchnik, Carolina, Nacmias, Benedetta, Ngandu, Tiia, Nicolas, Gael, Nordestgaard, Børge G., Olaso, Robert, Orellana, Adelina, Orsini, Michela, Ortega, Gemma, Padovani, Alessandro, Caffarra, Paolo, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Pérez-Cordón, Alba, Pérez-Tur, Jordi, Pericard, Pierre, Peters, Oliver, Pijnenburg, Yolande A.L., Pineda, Juan A, Piñol-Ripoll, Gerard, Pisanu, Claudia, Polak, Thomas, Popp, Julius, Posthuma, Danielle, Priller, Josef, Puerta, Raquel, Quenez, Olivier, Quintela, Inés, Thomassen, Jesper Qvist, Rábano, Alberto, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M, Reinders, Marcel J.T., Riedel-Heller, Steffi, Riederer, Peter, Rodriguez-Rodriguez, Eloy, Rongve, Arvid, Allende, Irene Rosas, Rosende-Roca, Maitée, Royo, Jose Luis, Rubino, Elisa, Rujescu, Dan, Sáez, María Eugenia, Sakka, Paraskevi, Saltvedt, Ingvild, Sanabria, Ángela, Sánchez-Arjona, María Bernal, Sanchez-Garcia, Florentino, Mehrabian, Shima, Sánchez-Juan, Pascual, Sánchez-Valle, Raquel, Sando, Sigrid B, Scamosci, Michela, Scarmeas, Nikolaos, Scarpini, Elio, Scheltens, Philip, Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias, Schneider, Anja, Schott, Jonathan M., Selbæk, Geir, Sha, Jin, Shadrin, Alexey A, Skrobot, Olivia, Snijders, Gijsje J. L., Soininen, Hilkka, Solfrizzi, Vincenzo, Solomon, Alina, Sorbi, Sandro, Sotolongo-Grau, Oscar, Spalletta, Gianfranco, Spottke, Annika, Squassina, Alessio, Tartari, Juan Pablo, Tárraga, Lluís, Tesí, Niccolo, Thalamuthu, Anbupalam, Tegos, Thomas, Traykov, Latchezar, Tremolizzo, Lucio, Tybjærg-Hansen, Anne, Uitterlinden, Andre, Ullgren, Abbe, Ulstein, Ingun, Valero, Sergi, Van Broeckhoven, Christine, van der Lugt, Aad, Van Dongen, Jasper, van Rooij, Jeroen, van Swieten, John, Vandenberghe, Rik, Verhey, Frans, Vidal, Jean-Sébastien, Vogelgsang, Jonathan, Vyhnalek, Martin, Wagner, Michael, Wallon, David, Wang, Li-San, Wang, Ruiqi, Weinhold, Leonie, Wiltfang, Jens, Windle, Gill, Woods, Bob, Yannakoulia, Mary, Zhao, Yi, Zulaica, Miren, Serrano-Rios, Manuel, Seripa, Davide, Stordal, Eystein, Farrer, Lindsay A., Psaty, Bruce M., Ghanbari, Mohsen, Raj, Towfique, Sachdev, Perminder, Mather, Karen, Jessen, Frank, Ikram, M. Arfan, de Mendonça, Alexandre, Hort, Jakub, Tsolaki, Magda, Pericak-Vance, Margaret A., Amouyel, Philippe, Williams, Julie, Frikke-Schmidt, Ruth, Clarimon, Jordi, Deleuze, Jean-François, Rossi, Giacomina, Seshadri, Sudha, Andreassen, Ole A., Ingelsson, Martin, Hiltunen, Mikko, Sleegers, Kristel, Schellenberg, Gerard D., van Duijn, Cornelia M., Sims, Rebecca, van der Flier, Wiesje M., Ruiz, Agustín, Ramirez, Alfredo, and Lambert, Jean-Charles

Subjects
0303 health sciences, Microglia, Amyloid, business.industry, Disease, medicine.disease, Bioinformatics, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Genetic etiology, Medicine, Dementia, Egfr signaling, business, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, and the failure to find effective treatments suggests that the underlying pathology remains poorly understood. Due to its strong heritability, deciphering the genetic landscape of AD and related dementia (ADD) is a unique opportunity to advance our knowledge. We completed a meta-analysis of genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases and 401,577 controls) with the most promising signals followed-up in 25,392 independent AD cases and 276,086 controls. We report 75 risk loci for ADD, including 42 novel ones. Pathway-enrichment analyses confirm the involvement of amyloid/Tau pathways, highlight the role of microglia and its potential interaction with APP metabolism. Numerous genes exhibited differential expression or splicing in AD-related conditions and gene prioritization implies EGFR signaling and TNF-α pathway through LUBAC complex. We also generated a novel polygenic risk score strongly associated with the risk of future dementia or progression from mild cognitive impairment to dementia. In conclusion, by more than doubling the number of loci associated with ADD risk, our study offers new insights into the pathophysiological processes underlying AD and offers additional therapeutic entry-points and tools for translational genomics.

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100. Evaluation of the Perioperative and Postoperative Course of Surgery for Pineal Germinoma in the SIOP CNS GCT 96 Trial

Author

Ehab Shabo, Thomas Czech, James C. Nicholson, Conor Mallucci, Carmine Mottolese, Gianluca Piatelli, Didier Frappaz, Matthew Jonathan Murray, Cecile Faure-Conter, Maria Luisa Garrè, Sevgi Sarikaya-Seiwert, Leonie Weinhold, Hannes Haberl, Gabriele Calaminus, Czech, Thomas [0000-0001-8112-2795], Nicholson, James C [0000-0001-9494-0199], Murray, Matthew Jonathan [0000-0002-4480-1147], Weinhold, Leonie [0000-0002-9194-9427], Calaminus, Gabriele [0000-0002-7893-7982], and Apollo - University of Cambridge Repository

Subjects
Cancer Research, perioperative course, Oncology, pineal germinoma, biopsy, resection, SIOP CNS GCT 96 trial
Abstract

Background: CNS germinoma, being marker-negative, are mainly diagnosed by histological examination. These tumors predominantly appear in the suprasellar and/or pineal region. In contrast to the suprasellar region, where biopsy is the standard procedure in case of a suspected germ-cell tumor to avoid mutilation to the endocrine structures, pineal tumors are more accessible to primary resection. We evaluated the perioperative course of patients with pineal germinoma who were diagnosed by primary biopsy or resection in the SIOP CNS GCT 96 trial. Methods: Overall, 235 patients had germinoma, with pineal localization in 113. The relationship between initial symptoms, tumor size, and postoperative complications was analyzed. Results: Of 111 evaluable patients, initial symptoms were headache (n = 98), hydrocephalus (n = 93), double vision (n = 62), Parinaud syndrome (n = 57), and papilledema (n = 44). There was no significant relationship between tumor size and primary symptoms. A total of 57 patients underwent primary resection and 54 underwent biopsy. Postoperative complications were reported in 43.2% of patients after resection and in 11.4% after biopsy (p < 0.008). Biopsy was significantly more commonly performed on larger tumors (p= 0.002). Conclusions: These results support the practice of biopsy over resection for histological confirmation of pineal germinoma.

Published
2022
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