New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Association Between Different Types Of Physical Activities And Quality Of Life In Women Aged 60 Years Or Over [associação Entre Diferentes Tipos De Atividades Físicas E Qualidade De Vida Em Mulheres Com 60 Ou Mais Anos De Idade]

Objective: To evaluate the association between different types of physical activity and quality of life in a sample of women aged 60 or over. Subjects and Methods: A cross-sectional study was carried out, interviewing 271 women. Of these, 141 were recruited in a menopause outpatient clinic and 130 were recruited in a social leisure center, in Brazil. The instruments used were the International Physical Activity Questionnaire (IPAQ) version 8 and the World Health Organization Quality of Life Questionnaire specific for this age group (WHOQOL-OLD). Each IPAQ section was evaluated by multiple linear regression analysis, considering independent and confounding variables. The significance level was set at 5% and the software used was SAS version 9.1.3. Results: The mean age of the patients was 67.4 ± 5.3 years. The mean time devoted to physical activity was 2802.7 ± 1154.9 minutes per week. The total WHOQOL-OLD score was 66.9 ± 11.7. The past, present and future actvities (estimated β = 0.021) and, social participation (estimated β = 0.03) domains had association with IPAQ transportation section. The leisure-time domain of the IPAQ had an inverse and significant relationship with the quality of life score related to present, past and future activities (estimated β = -0.0269). Conclusion: Quality of life was negatively influenced by leisure, but time spent in this physical activity was the shortest in comparison to other types of physical activities. In this sample, only physical activity for transportation was positively associated with a better quality of life. © 2011 Elsevier Editora Ltda.574450455Harman, D., The free radical theory of aging (2003) Antioxidants & Redox Signaling, pp. 557-561Spirduso, W.W., Francis, K.L., Macrae, P.G., (2005) Physical Dimensions Of Aging, , Champaign: Human KineticsPenedo, F.J., Dahn, J.R., Exercise and well-being: A review of mental physical health benefits associated with physical activity (2005) Curr Opin Psychiatry, 18 (2), pp. 189-193Bijnen, F.C., Caspersen, C.J., Feskens, E.J., Saris, W.H., Mosterd, W.L., Physical activity and 10-year mortality from cardiovascular diseases and all causes: The Zutphen Elderly Study (1998) Arch Intern Med, 158 (14), pp. 1499-1505Kvaavik, E., Batty, G.D., Ursin, G., Huxley, R., Gale, C.R., Influence of individual and combined health behaviors on total and cause-specific mortality in men and women: The United Kingdom health and lifestyle survey (2010) Arch Intern Med, 170 (8), pp. 711-718Sims, J., Hill, K., Hunt, S., Haralambous, B., Physical activity recommendations for older Australians (2009) Aust J Ageing, 29 (2), pp. 81-87Annear, M.J., Cushman, G., Gidlow, B., Leisure time physical activity differences among older adults from diverse socioeconomic neighborhoods (2009) Health Place, 15 (2), pp. 482-490Benedetti, T.B., Mazo, G.Z., Barros, M.V.G., Aplicação do questionário internacional de atividades físicas para avaliação do nível de atividades físicas de mulheres idosas: Validade concorrente e reprodutibilidade teste-reteste (2004) Rev Bras Ciênc Mov, 12 (1), pp. 25-34Hallal, P.C., Gomez, L.F., Parra, D.C., Lobelo, F., Mosquera, J., Florindo, A.A., Lessons learned after 10 years of IPAQ use in Brazil and Colombia (2010) J Phys Act Health, 7 (2 SUPPL), pp. S259-S264Franchi, K.M.B., Junior, R.M.M., Atividadefísica: Uma necessidade para boa saúde na terceira idade (2005) Rev Bras Promoç Saúde, 18 (3), pp. 152-156Jurakié, D., Pedisié, Z., Greblo, Z., Physical activity in different domains and health-related quality of life: A population-based study (2010) Qual Life Res, 19 (9), pp. 1303-1309Mazo, G.Z., Liposcki, D.B., Ananda, C., Prevê, D., Condições de saúde, incidência de quedas e nível de atividade física dos idosos (2007) Rev Bras Fisioter, 11 (6), pp. 437-442Benedetti, T.B., Mazo, G.Z., Barros, M.V.G., Aplicação do questionário internacional de atividades físicas para avaliação do nível de atividades físicas de mulheres idosas: Validade concorrente e reprodutibilidade teste-reteste (2004) Rev Bras Ciênc Mov, 12 (1), pp. 25-34Ferreira, M., Matsudo, S., Matsudo, V., Braggion, G., Efeitos de um programa de orientação de atividade física e nutricional sobre o nível de atividade física de mulheres fisicamente ativas de 50 a 72 anos de idade (2005) Rev Bras Med Esporte, 11 (3), pp. 172-176Fleck, M.P., Chachamovich, E., Trentini, C., Development and validation of the Portuguese version of the WHOQOL-OLD module (2006) Rev Saúde Pública, 40 (5), pp. 785-791Toscano, J.J.O., Oliveira, A.C.C., Qualidade de vida em idosos com distintos níveis de atividade física (2009) Rev Bras Med Esporte, 15 (3), pp. 169-173Sproston, K., Primatesta, P., (2004) Health Survey For England, , editors, Risk factors for cardiovascular disease. 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