Os desafios enfrentados pelos iniciantes na prática de enfermagem

O estudo teve o objetivo de investigar os desafios enfrentados pelas enfermeiras no início da profissão. As informações foram obtidas por entrevistas semiestruturadas de 31 profissionais de enfermagem formados entre 2000 a 2004. A análise foi feita pelo software Atlas Ti para análise qualitativa. Os recém-graduados enfrentaram desafios referentes às atividades: a) Relacionamento com a equipe de trabalho; b) Competência e habilidade técnica. Conclui-se que os recém-graduados estão pouco preparados para desempenhar a função de liderar uma equipe de enfermagem, bem como para o cuidado em unidades de alta complexidade. Para enfrentar esses desafios, novas estratégias de ensino e de prática devem ser traçadas de comum acordo entre docentes e enfermeira e enfermeiros atuantes na prática.Este estudio tuvo como objetivo investigar los desafíos enfrentados por las enfermeras en el inicio del ejercicio de su profesión. La recolección de datos fue efectuada a través de encuestas semiestructuradas, realizadas a 31 profesionales de enfermería que obtuvieron su graduación en el periodo de 2000 a 2004. El análisis fue efectuado con el software Atlas Ti para análisis cuantitativo. Los recién graduados enfrentaron desafíos en relación a: a) relación con el resto del equipo de trabajo; b) competencia y habilidad técnica. Se concluye en que los novatos están poco preparados para ejercer la función de liderar un equipo de enfermería y también para la atención en unidades de alta complejidad. Para enfrentar tales desafíos es necesario desarrollar nuevas estrategias de enseñanza y de práctica, en total acuerdo entre los docentes y profesionales con actuación efectiva.The purpose of the study was to investigate the challenges faced by the nurses during the first years of their nursing work. A total of 31 novice nurses were included in the sample that answered a questionnaire with open and closed questions. The data analysis was conducted by using the qualitative software called Atlas Ti. The novice nurses deal with some challenges related to: a) leadership team; b) the competence and technique ability. The findings suggested that the nursing novice is not well prepared for assuming a leadership role as well as for caring in the settings of high-complexity. In order to cope those challenges new strategies of education and nursing practice has to be developed together with nurses educators and nurses practitioners

Socioeconomic Inequalities in the Prevalence of Nine Established Cardiovascular Risk Factors in a Southern European Population

The evaluation of the gender-specific prevalence of cardiovascular risk factors across socioeconomic position (SEP) categories may unravel mechanisms involved in the development of coronary heart disease. Using a sample of 1704 community dwellers of a Portuguese urban center aged 40 years or older, assessed in 1999–2003, we quantified the age-standardized prevalence of nine established cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, smoking, sedentariness, abdominal obesity, poor diet, excessive alcohol intake and depression) across SEP and gender categories. Data on individual education and occupation were collected by questionnaire and used to characterize SEP. The prevalence of seven out of nine well-established risk factors was higher in men. Among women, the prevalence of most of the studied risk factors was higher in lower SEP groups. The main exception was smoking, which increased with education and occupation levels. Among men, socioeconomic gradients were less clear, but lower SEP was associated with a higher prevalence of diabetes, excessive alcohol intake and depression in a graded mode. The historical cultural beliefs and practices captured throughout the lifecourse frame the wide socioeconomic gradients discernible in our study conducted in an unequal European developed population. While men were more exposed to most risk factors, the clearer associations between SEP and risk factors among women support that their adoption of particular healthy behaviors is more dependent on material and symbolic conditions. To fully address the issue of health inequalities, interventions within the health systems should be complemented with population-based policies specifically designed to reduce socioeconomic gradients

LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies

Loss-of-function variants in the low-density lipoprotein receptor-related protein 10 (LRP10) gene have been associated with autosomal-dominant Parkinson's disease (PD), PD dementia, and dementia with Lewy bodies (DLB). Moreover, LRP10 variants have been found in individuals diagnosed with progressive supranuclear palsy and amyotrophic lateral sclerosis. Despite this genetic evidence, little is known about the expression and function of LRP10 protein in the human brain under physiological or pathological conditions. To better understand how LRP10 variants lead to neurodegeneration, we first performed an in-depth characterisation of LRP10 expression in post-mortem brains and human-induced pluripotent stem cell (iPSC)-derived astrocytes and neurons from control subjects. In adult human brain, LRP10 is mainly expressed in astrocytes and neurovasculature but undetectable in neurons. Similarly, LRP10 is highly expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived neurons. In astrocytes, LRP10 is present at trans-Golgi network, plasma membrane, retromer, and early endosomes. Interestingly, LRP10 also partially co-localises and interacts with sortilin-related receptor 1 (SORL1). Furthermore, although LRP10 expression and localisation in the substantia nigra of most idiopathic PD and DLB patients and LRP10 variant carriers diagnosed with PD or DLB appeared unchanged compared to control subjects, significantly enlarged LRP10-positive vesicles were detected in a patient carrying the LRP10 p.Arg235Cys variant. Last, LRP10 was detected in Lewy bodies (LB) at late maturation stages in brains from idiopathic PD and DLB patients and in LRP10 variant carriers. In conclusion, high LRP10 expression in non-neuronal cells and undetectable levels in neurons of control subjects indicate that LRP10-mediated pathogenicity is initiated via cell non-autonomous mechanisms, potentially involving the interaction of LRP10 with SORL1 in vesicle trafficking pathways. Together with the specific pattern of LRP10 incorporation into mature LBs, these data support an important mechanistic role for disturbed vesicle trafficking and loss of LRP10 function in neurodegenerative diseases

The program for biodiversity research in Brazil: The role of regional networks for biodiversity knowledge, dissemination, and conservation

The Program for Biodiversity Research (PPBio) is an innovative program designed to integrate all biodiversity research stakeholders. Operating since 2004, it has installed long-term ecological research sites throughout Brazil and its logic has been applied in some other southern-hemisphere countries. The program supports all aspects of research necessary to understand biodiversity and the processes that affect it. There are presently 161 sampling sites (see some of them at Supplementary Appendix), most of which use a standardized methodology that allows comparisons across biomes and through time. To date, there are about 1200 publications associated with PPBio that cover topics ranging from natural history to genetics and species distributions. Most of the field data and metadata are available through PPBio web sites or DataONE. Metadata is available for researchers that intend to explore the different faces of Brazilian biodiversity spatio-temporal variation, as well as for managers intending to improve conservation strategies. The Program also fostered, directly and indirectly, local technical capacity building, and supported the training of hundreds of undergraduate and graduate students. The main challenge is maintaining the long-term funding necessary to understand biodiversity patterns and processes under pressure from global environmental changes

Temporal patterns and trends of particulate matter over Portugal: a long-term analysis of background concentrations

Air quality management regarding PM concentrations in the atmosphere is a complex problem to tackle. In this paper, we aim to characterize the temporal patterns and trends of aerosol background levels over Portugal. Hourly data from the national air quality monitoring network, gathered from 2007 to 2016, is analyzed using statistical methods. Data from 20 monitoring stations was processed to prepare datasets with different time scales, and results were grouped by their type of surrounding area (urban, suburban, or rural). Urban and suburban background sites are characterized by strong seasonal patterns, with higher monthly mean concentrations in winter than in summer. In contrast, rural background PM10 concentrations are highest during August and September. This study suggests that urban background concentrations are significantly influenced by anthropogenic non-combustion sources, which contribute to the coarser aerosol fraction (PMc). PMc is about 3 μg m−3 higher during weekdays than during Sundays, at urban sites. However, there is no clear relationship between the value of the PM2.5/PMc ratio and the type of monitoring station. During the 10-year period of study, a decrease of 1.83, 3.58, and 4.89%/year was registered in PM10 concentrations at Portuguese rural, urban, and suburban areas, respectively. Despite the higher decrease at suburban monitoring stations, those sites present the highest 10-year mean PM10 concentrations. This work provides an import insight on temporal variations of PM10, PM2.5, and PMc concentrations over Portugal and summarizes trends through the last decade, contributing to the discussion on sources and processes influencing those concentrations.Thanks also are due to the Portuguese Agency for the Environment (APA) and the Regional Coordination and Development Commissions (CCDRs) for their effort in establishing and maintaining the air quality monitoring sites used in this investigation.publishe

O ambiente educacional do curso de Graduação em Enfermagem na perspectiva dos estudantes

RESUMO Objetivo Avaliar o ambiente educacional da Escola de Enfermagem da Universidade de São Paulo, na perspectiva do estudante. Método Abordagem quantitativa com desenho exploratório. Participaram do estudo, 176 estudantes que responderam a uma escala Likert, com graduação de 1 a 5 para avaliação do ambiente educacional. Os dados foram submetidos à análise fatorial exploratóriae testes estatísticos inferenciais; a confiabilidade do instrumento foi constatada pelo Alpha de Cronbach. Resultados A análise de dimensionalidade estabeleceu quatro fatores: Suporte à aprendizagem prática, com média de escore 3,64; Atitudes durante a aprendizagem, escore médio 2,92; Clima de aprendizagem, média 3,58 e Fragilidades da aprendizagem com 3,04. Conclusão O fator mais favorável do ambiente foi o Suporte à aprendizagem. As competências atitudinais atingiram escores mais baixos, sugerindo a necessidade de fortalecer esses aspectos durante a graduação

Prevalence and risk factors for intestinal protozoa infection in elderly residents at Long Term Residency Institutions in Southeastern Brazil

This study determined the prevalence of intestinal protozoa in Long Term Residency Institutions for the Elderly (ILPI) in elders, nurses and food handlers, identifying the risk factors associated with the infections. Stool samples taken from the elderly (n = 293), nurses (63) and food handlers (19) were studied. Questionnaires were used with questions related to sociodemographic variables, health, behavior and health characteristics. Stool samples were examined using the techniques of Faust and Ziehl Neelsen, and the prevalence of G. duodenalis, Cryptosporidium spp., E. histolytica/dispar in the elderly was 4.0%, 1.0% and 0.3% respectively. Nurses and food handlers showed 4.8% and 5.2% positivity only for G. duodenalis, respectively. The origin of the individuals and contact with domestic animals has been associated with infection by G. duodenalis in the elderly, and contact with domestic animals was considered a risk factor for infection. The last stool examinations were related to Cryptosporidium spp.. None of the variables were associated with E. histolytica/dispar. The frequency of hand washing was significantly associated with G. duodenalis among nurses. The frequency of positive samples of G. duodenalis, Cryptosporidium spp., E. histolytica/dispar showed that ILPIs environments are conducive to this occurring due to contact between the elderly, nurses and food handlers, which are often poorly trained in hygiene procedures and food handling

Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly 1 , and risk is partially driven by genetics 2 . Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS) 3–8 . To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci ( IQCK , ACE , ADAM10 , and ADAMTS1 ). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ) indicating that additional rare variants remain to be identified.ADGC. The National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; Samples from the National Cell Repository for Alzheimer’s Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible; Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689-01); NACC, U01 AG016976; NIA LOAD (Columbia University), U24 AG026395, U24 AG026390, R01AG041797; Banner Sun Health Research Institute P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG048927, R01AG33193, R01 AG009029; Columbia University, P50 AG008702, R37 AG015473, R01 AG037212, R01 AG028786; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG006781, UO1 HG004610, UO1 HG006375, U01 HG008657; Indiana University, P30 AG10133, R01 AG009956, RC2 AG036650; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574, R01 AG032990, KL2 RR024151; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; North Carolina A&T University, P20 MD000546, R01 AG28786-01A1; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG030146, R01 AG01101, RC2 AG036650, R01 AG22018; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653, AG041718, AG07562, AG02365; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136, R01 AG042437; University of Wisconsin, P50 AG033514; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991, P01 AG026276. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant # NS39764, NIMH MH60451 and by Glaxo Smith Kline. Support was also from the Alzheimer’s Association (LAF, IIRG-08-89720; MP-V, IIRG-05-14147), the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program, and BrightFocus Foundation (MP-V, A2111048). P.S.G.-H. is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232 to AJM and MJH, The Banner Alzheimer’s Foundation, The Johnnie B. Byrd Sr. Alzheimer’s Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council),South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer’s Research Trust (ART), BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona. ADNI data collection and sharing was funded by the National Institutes of Health Grant U01 AG024904 and 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.; Eisai Inc.; Elan Pharmaceuticals, 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 & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & 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 Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. We thank Drs. D. Stephen Snyder and Marilyn Miller from NIA who are ex-officio ADGC members. EADI. This work has been developed and supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease) including funding from MEL (Metropole européenne de Lille), ERDF (European Regional Development Fund) and Conseil Régional Nord Pas de Calais. This work was supported by INSERM, the National Foundation for Alzheimer’s disease and related disorders, the Institut Pasteur de Lille and the Centre National de Génotypage, the JPND PERADES, GENMED, and the FP7 AgedBrainSysBio. The Three-City Study was performed as part of 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. The 3C Study was also funded by 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, Agence Nationale de la Recherche, ANR supported the COGINUT and COVADIS projects. 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. The Three-city biological bank was developed and maintained by the laboratory for genomic analysis LAG-BRC - Institut Pasteur de Lille. This work was further supported by the CoSTREAM project (http://www.costream.eu/) and funding from the European Union's Horizon 2020 research and innovation program under grant agreement 667375. Belgium samples: Research at the Antwerp site is funded in part by the Belgian Science Policy Office Interuniversity Attraction Poles program, the Belgian Alzheimer Research Foundation, the Flemish government-initiated Flanders Impulse Program on Networks for Dementia Research (VIND) and the Methusalem excellence program, the Research Foundation Flanders (FWO), and the University of Antwerp Research Fund, Belgium. The Antwerp site authors thank the personnel of the VIB Neuromics Support Facility, the Biobank of the Institute Born-Bunge and neurology departments at the contributing hospitals. The authors acknowledge the members of the BELNEU consortium for their contributions to the clinical and pathological characterization of Belgium patients and the personnel of the Diagnostic Service Facility for the genetic testing. Finish sample collection: Financial support for this project was provided by Academy of Finland (grant number 307866), Sigrid Jusélius Foundation and the Strategic Neuroscience Funding of the University of Eastern Finland. Swedish sample collection: Financially supported in part by the Swedish Brain Power network, the Marianne and Marcus Wallenberg Foundation, the Swedish Research Council (521-2010-3134, 2015-02926), the King Gustaf V and Queen Victoria’s Foundation of Freemasons, the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and the Karolinska Institutet, the Swedish Brain Foundation and the Swedish Alzheimer Foundation”. CHARGE. Infrastructure for the CHARGE Consortium is supported in part by National Heart, Lung, and Blood Institute grant HL105756 (Psaty) and RC2HL102419 (Boerwinkle) and the neurology working group by grants from the National Institute on Aging, R01 AG033193, U01 AG049505 and U01AG52409. Rotterdam (RS). This study was funded by the Netherlands Organisation for Health Research and Development (ZonMW) as part of the Joint Programming for Neurological Disease (JPND)as part of the PERADES Program (Defining Genetic Polygenic, and Environmental Risk for Alzheimer’s disease using multiple powerful cohorts, focused Epigenetics and Stem cell metabolomics), Project number 733051021. This work was funded also by the European Union Innovative Medicine Initiative (IMI) programme under grant agreement No. 115975 as part of the Alzheimer’s Disease Apolipoprotein Pathology for Treatment Elucidation and Development (ADAPTED, https://www.imi-adapted.eu);and the European Union’s Horizon 2020 research and innovation programme as part of the Common mechanisms and pathways in Stroke and Alzheimer’s disease CoSTREAM project (www.costream.eu, grant agreement No. 667375). The current study is supported by the Deltaplan Dementie and Memorabel supported by ZonMW (Project number 733050814) and Alzheimer Nederland. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study (RS-I, RS-II, RS-III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organization of Scientific Research NWO Investments (Project number 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project number 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina Medina-Gomez, MSc, for the creation and analysis of imputed data. AGES. The AGES study has been funded by NIA contracts N01-AG-12100 and HHSN271201200022C with contributions from NEI, NIDCD, and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). Cardiovascular Health Study (CHS). This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG033193, R01AG023629, R01AG15928, and R01AG20098 and by U01AG049505 from the National Institute on Aging (NIA). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. A full list of CHS principal investigators and institutions can be found at https://chs-nhlbi.org/. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. Framingham Heart Study. This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contracts N01-HC-25195 and HHSN268201500001I). This study was also supported by grants from the National Institute on Aging: R01AG033193, U01AG049505, U01AG52409, R01AG054076 (S. Seshadri). S. Seshadri and A.L.D. were also supported by additional grants from the National Institute on Aging (R01AG049607, R01AG033040) and the National Institute of Neurological Disorders and Stroke (R01- NS017950, NS100605). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. GR@ACE cohort. Fundació ACE We would like to thank patients and controls who participated in this project. Genome Resesarch @ Fundació ACE project (GR@ACE) is supported by Fundación bancaria “La Caixa”, Grifols SA, Fundació ACE and ISCIII. We also want to thank other private sponsors supporting the basic and clinical projects of our institution (Piramal AG, Laboratorios Echevarne, Araclon Biotech S.A. and Fundació ACE). We are indebted to Trinitat Port-Carbó legacy and her family for their support of Fundació ACE research programs. Fundació ACE collaborates with the Centro de Investigación Biomédica en Red sobreEnfermedades Neurodegenerativas (CIBERNED, Spain) and is one of the participating centers of the Dementia Genetics Spanish Consortium (DEGESCO). A.R. and M.B. are receiving support from the European Union/EFPIA Innovative Medicines Initiative Joint Undertaking ADAPTED and MOPEAD projects (Grants No. 115975 and 115985 respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861 and PI17/01474. Acción Estratégica en Salud integrated in 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”). 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) and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. GERAD/PERADES. We thank all individuals who participated in this study. Cardiff University was supported by the Wellcome Trust, Alzheimer’s Society (AS; grant RF014/164), the Medical Research Council (MRC; grants G0801418/1, MR/K013041/1, MR/L023784/1), the European Joint Programme for Neurodegenerative Disease (JPND, grant MR/L501517/1), Alzheimer’s Research UK (ARUK, grant ARUK-PG2014-1), Welsh Assembly Government (grant SGR544:CADR), a donation from the Moondance Charitable Foundation, and the UK Dementia Research Institute at Cardiff. Cambridge University acknowledges support from the MRC. ARUK supported sample collections at the Kings College London, the South West Dementia Bank, Universities of Cambridge, Nottingham, Manchester and Belfast. King’s College London was supported by the NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and Kings College London and the MRC. Alzheimer’s Research UK (ARUK) and the Big Lottery Fund provided support to Nottingham University. Ulster Garden Villages, AS, ARUK, American Federation for Aging Research, NI R&D Office and the Royal College of Physicians/Dunhill Medical Trust provided support for Queen’s University, Belfast. The University of Southampton acknowledges support from the AS. The MRC and Mercer’s Institute for Research on Ageing supported the Trinity College group. DCR is a Wellcome Trust Principal Research fellow. The South West Dementia Brain Bank acknowledges support from Bristol Research into Alzheimer’s and Care of the Elderly. The Charles Wolfson Charitable Trust supported the OPTIMA group. Washington University was funded by NIH grants, Barnes Jewish Foundation and the Charles and Joanne Knight Alzheimer’s Research Initiative. Patient recruitment for the MRC Prion Unit/UCL Department of Neurodegenerative Disease collection was supported by the UCLH/UCL Biomed- ical Centre and their work was supported by the NIHR Queen Square Dementia BRU. LASER-AD was funded by Lundbeck SA. The Bonn group would like to thank Dr. Heike Koelsch for her scientific support. The Bonn group was funded by the German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant number 01GI0102, 01GI0711, 01GI0420. The AgeCoDe study group was supported by the German Federal Ministry for Education and Research grants 01 GI 0710, 01 GI 0712, 01 GI 0713, 01 GI 0714, 01 GI 0715, 01 GI 0716, 01 GI 0717. Genotyping of the Bonn case-control sample was funded by the German centre for Neurodegenerative Diseases (DZNE), Germany. The GERAD Consortium also used samples ascertained by the NIMH AD Genetics Initiative. HH was supported by a grant of the Katharina-Hardt-Foundation, Bad Homburg vor der Höhe, Germany. The KORA F4 studies were financed by Helmholtz Zentrum München; German Research Center for Environmental Health; BMBF; German National Genome Research Network and the Munich Center of Health Sciences. The Heinz Nixdorf Recall cohort was funded by the Heinz Nixdorf Foundation (Dr. Jur. G.Schmidt, Chairman) and BMBF. Coriell Cell Repositories is supported by NINDS and the Intramural Research Program of the National Institute on Aging. We acknowledge use of genotype data from the 1958 Birth Cohort collection, funded by the MRC and the Wellcome Trust which was genotyped by the Wellcome Trust Case Control Consortium and the Type-1 Diabetes Genetics Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development and Juvenile Diabetes Research Foundation International. The Bonn samples are part of the German Dementia Competance Network (DCN) and the German Research Network on Degenerative Dementia (KNDD), which are funded by the German Federal Ministry of Education and Research (grants KND: 01G10102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 04GI0434; grants KNDD: 01GI1007A, 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B). Markus M Nothen is a member of the German Research Foundation (DFG) cluster of excellence ImmunoSensation. Funding for Saarland University was provided by the German Federal Ministry of Education and Research (BMBF), grant number 01GS08125 to Matthias Riemenschneider. The University of Washington was supported by grants from the National Institutes of Health (R01-NS085419 and R01-AG044546), the Alzheimer’s Association (NIRG-11-200110) and the American Federation for Aging Research (Carlos Cruchaga was recipient of a New Investigator Award in Alzhei