Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?

The increase in life expectancy has led in recent years to neurodegenerative pathologies, such as Alzheimer’s disease, that were strange in the last century, now become so frequent that there is talk of a new epidemic. It is estimated that approximately 50000000 patients suffer dementia around the w...

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Autores:
Allegri, Ricardo Francisco
Tipo de recurso:
Article of investigation
Fecha de publicación:
2021
Institución:
Corporación Universidad de la Costa
Repositorio:
REDICUC - Repositorio CUC
Idioma:
eng
OAI Identifier:
oai:repositorio.cuc.edu.co:11323/13223
Acceso en línea:
https://hdl.handle.net/11323/13223
https://repositorio.cuc.edu.co/
Palabra clave:
Alzheimer’s
Neurodegenerative pathologies
Dementia
Rights
openAccess
License
Atribución 4.0 Internacional (CC BY 4.0)
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repository_id_str
dc.title.eng.fl_str_mv Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
title Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
spellingShingle Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
Alzheimer’s
Neurodegenerative pathologies
Dementia
title_short Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
title_full Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
title_fullStr Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
title_full_unstemmed Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
title_sort Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?
dc.creator.fl_str_mv Allegri, Ricardo Francisco
dc.contributor.author.none.fl_str_mv Allegri, Ricardo Francisco
dc.subject.proposal.eng.fl_str_mv Alzheimer’s
Neurodegenerative pathologies
Dementia
topic Alzheimer’s
Neurodegenerative pathologies
Dementia
description The increase in life expectancy has led in recent years to neurodegenerative pathologies, such as Alzheimer’s disease, that were strange in the last century, now become so frequent that there is talk of a new epidemic. It is estimated that approximately 50000000 patients suffer dementia around the world (World Health OrganizationWHO, 2012). Alzheimer’s disease is the most common dementia, and brain pathology begin up to 25 years before the first clinical symptoms appear (Bateman et al., 2012). Thus, Alzheimer currently has five stages, the pre-symptomatic, the mild cognitive impairment, and the mild, moderate and severe dementia. Since the original description in 1904 by Alois Alzheimer, the disease could only be definitively diagnosed by neuropathological, and the clinical diagnosis was only probable or possible (NINCDS ADRDA, McKhan et al., 1984). In recent years, more detailed knowledge of structural neuroimaging (hippocampal volume by MRI), metabolic (FDG-PET), molecular (amyloid PET), and cerebrospinal fluid studies (Aβ42, tau and f-tau) make it possible to diagnose Dementia due to Alzheimer’s disease while the patient is alive (McKhan et al., 2011) and even at pre-symptomatic stage of the disease (Sperling et al, 2011).
publishDate 2021
dc.date.issued.none.fl_str_mv 2021-09-10
dc.date.accessioned.none.fl_str_mv 2024-07-29T21:50:13Z
dc.date.available.none.fl_str_mv 2024-07-29T21:50:13Z
dc.type.spa.fl_str_mv Artículo de revista
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dc.type.content.spa.fl_str_mv Text
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dc.identifier.citation.spa.fl_str_mv Allegri, R. F. (2021). Editorial. Towards 2022: What are prevention and risk reduction in Alzheimer’s disease? Journal of Apllied Cognitive Neuroscience, 2(2), e00004009. https://doi.org/10.17981/JACN.2.2.2021.00
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/11323/13223
dc.identifier.doi.none.fl_str_mv 10.17981/JACN.2.2.2021.00
dc.identifier.eissn.spa.fl_str_mv 2745-0031
dc.identifier.instname.spa.fl_str_mv Corporación Universidad de la Costa
dc.identifier.reponame.spa.fl_str_mv REDICUC - Repositorio CUC
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identifier_str_mv Allegri, R. F. (2021). Editorial. Towards 2022: What are prevention and risk reduction in Alzheimer’s disease? Journal of Apllied Cognitive Neuroscience, 2(2), e00004009. https://doi.org/10.17981/JACN.2.2.2021.00
10.17981/JACN.2.2.2021.00
2745-0031
Corporación Universidad de la Costa
REDICUC - Repositorio CUC
url https://hdl.handle.net/11323/13223
https://repositorio.cuc.edu.co/
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournal.spa.fl_str_mv Journal of Applied Cognitive Neuroscience
dc.relation.references.spa.fl_str_mv Bateman, R. J.; Xiong, C.; Benzinger, T.; Fagan, A. M.; Goate, A.; Fox, N. C.; Marcus, D. S.; Cairns, N. J.; Xie, X., Blazey, T. M.; Holtzman, D. M.; Santacruz, A.; Buckles, V.; Oliver, A.; Moulder, K.; Aisen, P. S.; Ghetti, B.; Klunk, W. E.; McDade, E.; Martins, R. N.; Masters, C. L.; Mayeux, R.; Ringman, J. M.; Rossor, M. N.; Schofield, P. R.; Sperling, R. A.; Salloway, S. & Morris, J. C. (2012). Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s disease. The New England Journal of Medicine, 367(9), 795–804. https://doi.org/10.1056/NEJMoa1202753
Brookmeyer, R.; Johnson, E.; Ziegler-Graham, K. & Arrighi, H. M. (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimer’s & Dementia, 3(3), 186–191. https://doi.org/10.1016/j.jalz.2007.04.381
Cummings, J.; Lee, G.; Zhong, K.; Fonseca, J. & Taghva, K. (2021). Alzheimer’s disease drug development pipeline: 2021. Alzheimer’s Dement, 7(1), 1–24. https://doi.org/10.1002/trc2.12179
Feinleib, M. (2001). A Dictionary of Epidemiology, Fourth Edition - Edited by John M. Last, Robert A. Spasoff, and Susan S. Harris. American Journal of Epidemiology, 154(1), 93–94. https://doi.org/10.1093/aje/154.1.93-a
Getsios, D.; Blume, S.; Ishak, K. J.; Maclaine, G. & Hernández, L. (2012). An economic evaluation of early assessment for Alzheimer’s disease in the United Kigdom. Alzheimer & Dementia, 8(1), 22–30. https://doi.org/10.1016/j.jalz.2010.07.001
Journal of Applied Cognitive Neuroscience, vol. 2 no. 2, e00004009, July - December, 2021 Hodes, J. F.; Oakley, C. L.; O’Keefe, J. H.; Lu, P.; Galvin, J. E.; Saif, N.; Bellara, S.; Rahman, A.; Kaufman, Y.; Hristov, H.; Rajji, T. K.; Fosnacht, A. M.; Patel, S.; Merrill, D. A.; Kaiser, S.; Meléndez-Cabrero, J.; Melendez, J. A.; Krikorian, R. & Isaacson, R. S. (2019). Alzheimer’s “Prevention ”vs.“ Risk Reduction: Transcending Semantics for Clinical Practice. Frontiers in Neurology, 9(1), 1–8. https://doi.org/10.3389/fneur.2018.01179
Kivipelto, M.; Mangialasche, F.; Snyder, H. M.; Allegri, R. F.; Andrieu, S.; Arai, H.; Baker, L.; Belleville, S.; Brodaty, H.; Brucki, S. M.; Calandri, I.; Caramelli, P.; Chen, C.; Chertkow, H.; Chew, E.; Choi, S. H.; Chowdhary, N.; Crivelli, L.; De La Torre, R.; Du, Y.;Dua, T.; Espeland, M.; Feldman, H. H.; Hartmanis, M.; Hartmann, T.; Heffernan, M.; Henry, C. J.; Hong, C. H.; Håkansson, K.; Iwatsubo, T.; Jeong, J. H.; Jimenez-Maggiora, G.; Koo, E. H.; Launer, L. J.; Lehtisalo, J.; Lopera, F.; Martínez-Lage, P.; Martins, R.; Middleton, L.; Molinuevo, J. L.; MonteroOdasso, M.; Moon, S. Y.; Morales-Pérez, K.; Nitrini, R.; Nygaard, H. B.; Park, Y. K.; Peltonen, M.; Qiu, C.; Quiroz, Y. T.; Raman, R.; Rao, N.; Ravindranath, V.; Rosenberg, A.; Sakurai, T.; Salinas, R. M.; Scheltens, P.; Sevlever, G.; Soininen, H.; Sosa, A. L.; Suemoto, C. K.; Tainta-Cuezva, M.; Velilla, L.; Wang, Y.; Whitmer, R.; Xu, X.; Bain, L. J.; Solomon, A.; Ngandu, T. & Carrillo, M. C. (2020). World-Wide FINGERS Network: A Global Approach to Risk Reduction and Prevention of Dementia. Alzheimers & Dement, 16(1), 1078–1094. https://doi.org/10.1002/alz.12123
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D. & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDAWork Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology, 34(7), 939–944. https://doi.org/10.1212/wnl.34.7.939
McKhann, G. M.; Knopman, D. S.; Chertkow, H.; Hyman, B. T.; Jack, C. R. Jr, Kawas, C. H, Klunk, W. E; Koroshetz, W. J.; Manly, J. J.; Mayeux, R.; Mohs, R. C.; Morris, J. C.; Rossor, M. N.; Scheltens, P.; Carrillo, M. C.; Thies, B.; Weintraub, S. & Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging– Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7(3), 263–269. https://doi.org/10.1016/j.jalz.2011.03.005
Prince, M.; Bryce, R. & Ferri, C. (2011). World Alzheimer Report 2011. The benefits of early diagnosis and intervention. London: ADI. Available: https://www.alzint.org/resource/world-alzheimer-report-2011/
Sperling, R. A.; Aisen, P. S.; Beckett, L. A.; Bennett, D. A.; Craft, S.; Fagan, A. M.; Iwatsubo, T.; Jack Jr, C. R.; Kaye, J.; Montine, T. J.; Park, D. C.; Reiman, E. M.; Rowe, C. C.; Siemers, E.; Stern, Y.; Yaffe, K.; Carrillo, M. C.; Thies, B.; MorrisonBogorad, M.; Wagster, M. V. & Phelps, C. H. (2011). Towards defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7, 280–292. https://doi.org/10.1016/j.jalz.2011.03.003
WHO EMRO. (feb. 1, 2015). Health Promotion and Disease Prevention Through Population-Based Interventions, Including Action to Address Social Determinants and Health Inequity. Genebra: Regional Director/WHO. Available: http://www.emro.who.int/about-who/public-health-functions/health-promotiondisease-prevention.html
WHO. (2012). Dementia: A Public Health Priority. London: WHO/ADI. Available: https://apps.who.int/iris/handle/10665/75263
Wimo, A. & Prince, M. (2010). World Alzheimer Report 2010. London: ADI. Available from https://www.alz.org/documents/national/world_alzheimer_report_2010.pdf
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dc.rights.eng.fl_str_mv © 2021 Ricardo F. Allegri
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spelling Atribución 4.0 Internacional (CC BY 4.0)© 2021 Ricardo F. Allegrihttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Allegri, Ricardo Francisco20222024-07-29T21:50:13Z2024-07-29T21:50:13Z2021-09-10Allegri, R. F. (2021). Editorial. Towards 2022: What are prevention and risk reduction in Alzheimer’s disease? Journal of Apllied Cognitive Neuroscience, 2(2), e00004009. https://doi.org/10.17981/JACN.2.2.2021.00https://hdl.handle.net/11323/1322310.17981/JACN.2.2.2021.002745-0031Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/The increase in life expectancy has led in recent years to neurodegenerative pathologies, such as Alzheimer’s disease, that were strange in the last century, now become so frequent that there is talk of a new epidemic. It is estimated that approximately 50000000 patients suffer dementia around the world (World Health OrganizationWHO, 2012). Alzheimer’s disease is the most common dementia, and brain pathology begin up to 25 years before the first clinical symptoms appear (Bateman et al., 2012). Thus, Alzheimer currently has five stages, the pre-symptomatic, the mild cognitive impairment, and the mild, moderate and severe dementia. Since the original description in 1904 by Alois Alzheimer, the disease could only be definitively diagnosed by neuropathological, and the clinical diagnosis was only probable or possible (NINCDS ADRDA, McKhan et al., 1984). In recent years, more detailed knowledge of structural neuroimaging (hippocampal volume by MRI), metabolic (FDG-PET), molecular (amyloid PET), and cerebrospinal fluid studies (Aβ42, tau and f-tau) make it possible to diagnose Dementia due to Alzheimer’s disease while the patient is alive (McKhan et al., 2011) and even at pre-symptomatic stage of the disease (Sperling et al, 2011).8 páginasapplication/pdfengUniversidad de la Costa, CUCBarranquillahttps://revistascientificas.cuc.edu.co/JACN/article/view/4009Towards 2022: what are prevention and risk reduction in Alzheimer’s disease?Artículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Journal of Applied Cognitive NeuroscienceBateman, R. J.; Xiong, C.; Benzinger, T.; Fagan, A. M.; Goate, A.; Fox, N. C.; Marcus, D. S.; Cairns, N. J.; Xie, X., Blazey, T. M.; Holtzman, D. M.; Santacruz, A.; Buckles, V.; Oliver, A.; Moulder, K.; Aisen, P. S.; Ghetti, B.; Klunk, W. E.; McDade, E.; Martins, R. N.; Masters, C. L.; Mayeux, R.; Ringman, J. M.; Rossor, M. N.; Schofield, P. R.; Sperling, R. A.; Salloway, S. & Morris, J. C. (2012). Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s disease. The New England Journal of Medicine, 367(9), 795–804. https://doi.org/10.1056/NEJMoa1202753Brookmeyer, R.; Johnson, E.; Ziegler-Graham, K. & Arrighi, H. M. (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimer’s & Dementia, 3(3), 186–191. https://doi.org/10.1016/j.jalz.2007.04.381Cummings, J.; Lee, G.; Zhong, K.; Fonseca, J. & Taghva, K. (2021). Alzheimer’s disease drug development pipeline: 2021. Alzheimer’s Dement, 7(1), 1–24. https://doi.org/10.1002/trc2.12179Feinleib, M. (2001). A Dictionary of Epidemiology, Fourth Edition - Edited by John M. Last, Robert A. Spasoff, and Susan S. Harris. American Journal of Epidemiology, 154(1), 93–94. https://doi.org/10.1093/aje/154.1.93-aGetsios, D.; Blume, S.; Ishak, K. J.; Maclaine, G. & Hernández, L. (2012). An economic evaluation of early assessment for Alzheimer’s disease in the United Kigdom. Alzheimer & Dementia, 8(1), 22–30. https://doi.org/10.1016/j.jalz.2010.07.001Journal of Applied Cognitive Neuroscience, vol. 2 no. 2, e00004009, July - December, 2021 Hodes, J. F.; Oakley, C. L.; O’Keefe, J. H.; Lu, P.; Galvin, J. E.; Saif, N.; Bellara, S.; Rahman, A.; Kaufman, Y.; Hristov, H.; Rajji, T. K.; Fosnacht, A. M.; Patel, S.; Merrill, D. A.; Kaiser, S.; Meléndez-Cabrero, J.; Melendez, J. A.; Krikorian, R. & Isaacson, R. S. (2019). Alzheimer’s “Prevention ”vs.“ Risk Reduction: Transcending Semantics for Clinical Practice. Frontiers in Neurology, 9(1), 1–8. https://doi.org/10.3389/fneur.2018.01179Kivipelto, M.; Mangialasche, F.; Snyder, H. M.; Allegri, R. F.; Andrieu, S.; Arai, H.; Baker, L.; Belleville, S.; Brodaty, H.; Brucki, S. M.; Calandri, I.; Caramelli, P.; Chen, C.; Chertkow, H.; Chew, E.; Choi, S. H.; Chowdhary, N.; Crivelli, L.; De La Torre, R.; Du, Y.;Dua, T.; Espeland, M.; Feldman, H. H.; Hartmanis, M.; Hartmann, T.; Heffernan, M.; Henry, C. J.; Hong, C. H.; Håkansson, K.; Iwatsubo, T.; Jeong, J. H.; Jimenez-Maggiora, G.; Koo, E. H.; Launer, L. J.; Lehtisalo, J.; Lopera, F.; Martínez-Lage, P.; Martins, R.; Middleton, L.; Molinuevo, J. L.; MonteroOdasso, M.; Moon, S. Y.; Morales-Pérez, K.; Nitrini, R.; Nygaard, H. B.; Park, Y. K.; Peltonen, M.; Qiu, C.; Quiroz, Y. T.; Raman, R.; Rao, N.; Ravindranath, V.; Rosenberg, A.; Sakurai, T.; Salinas, R. M.; Scheltens, P.; Sevlever, G.; Soininen, H.; Sosa, A. L.; Suemoto, C. K.; Tainta-Cuezva, M.; Velilla, L.; Wang, Y.; Whitmer, R.; Xu, X.; Bain, L. J.; Solomon, A.; Ngandu, T. & Carrillo, M. C. (2020). World-Wide FINGERS Network: A Global Approach to Risk Reduction and Prevention of Dementia. Alzheimers & Dement, 16(1), 1078–1094. https://doi.org/10.1002/alz.12123McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D. & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDAWork Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology, 34(7), 939–944. https://doi.org/10.1212/wnl.34.7.939McKhann, G. M.; Knopman, D. S.; Chertkow, H.; Hyman, B. T.; Jack, C. R. Jr, Kawas, C. H, Klunk, W. E; Koroshetz, W. J.; Manly, J. J.; Mayeux, R.; Mohs, R. C.; Morris, J. C.; Rossor, M. N.; Scheltens, P.; Carrillo, M. C.; Thies, B.; Weintraub, S. & Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging– Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7(3), 263–269. https://doi.org/10.1016/j.jalz.2011.03.005Prince, M.; Bryce, R. & Ferri, C. (2011). World Alzheimer Report 2011. The benefits of early diagnosis and intervention. London: ADI. Available: https://www.alzint.org/resource/world-alzheimer-report-2011/Sperling, R. A.; Aisen, P. S.; Beckett, L. A.; Bennett, D. A.; Craft, S.; Fagan, A. M.; Iwatsubo, T.; Jack Jr, C. R.; Kaye, J.; Montine, T. J.; Park, D. C.; Reiman, E. M.; Rowe, C. C.; Siemers, E.; Stern, Y.; Yaffe, K.; Carrillo, M. C.; Thies, B.; MorrisonBogorad, M.; Wagster, M. V. & Phelps, C. H. (2011). Towards defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7, 280–292. https://doi.org/10.1016/j.jalz.2011.03.003WHO EMRO. (feb. 1, 2015). Health Promotion and Disease Prevention Through Population-Based Interventions, Including Action to Address Social Determinants and Health Inequity. Genebra: Regional Director/WHO. Available: http://www.emro.who.int/about-who/public-health-functions/health-promotiondisease-prevention.htmlWHO. (2012). Dementia: A Public Health Priority. London: WHO/ADI. Available: https://apps.who.int/iris/handle/10665/75263Wimo, A. & Prince, M. (2010). World Alzheimer Report 2010. London: ADI. 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y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.

d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:

i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.

ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.

e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.

5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

7. Término.

a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.

b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.

8. Varios.

a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.

b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.

c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.

d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.
