Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City
While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging d...
- Autores:
-
Sosa, Ana Luisa
Brucki, Sonia MD
Crivelli, Lucia
Lopera, Francisco Javier
Acosta, Daisy M
Acosta-Uribe, Juliana
Aguilar, Diego
Aguilar-Navarro, Sara G
Allegri, Ricardo F
Bertolucci, Paulo HF
Calandri, Ismael L
Carrillo, Maria C
Chrem Méndez, Patricio Alexis
Cornejo-Olivas, Mario
Custodio, Nilton
Damian, Andrés
Cruz de Souza, Leonardo
Duran-Aniotz, Claudia
García, Adolfo M
García-Peña, Carmen
Gonzales, Mitzi M
Grinberg, Lea T
Ibáñez, Agustín M
Illanes-Manrique, Maryenela Zaida
Jack Jr, Clifford R
Leon-Salas, Jorge Mario
Llibre-Guerra, Jorge J
Luna-Muñoz, José
Matallana, Diana
Miller, Bruce L
Naci, Lorina
Parra, Mario A
Pericak-Vance, Margaret
Piña-Escudero, Stefanie D
França Resende, Elisa de Paula
Ringman, John M
Sevlever, Gustavo
Slachevsky, Andrea
Kimie Suemoto, Claudia
Valcour, Victor
Villegas-Lanau, Andres
Yassuda, Mônica S
Mahinrad, Simin
Sexton, Claire
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2024
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/13363
- Acceso en línea:
- https://hdl.handle.net/11323/13363
https://repositorio.cuc.edu.co/
- Palabra clave:
- Alzheimer’s disease
Biomarkers
Dementia
Genetics
Hispanics
Latin America
- Rights
- openAccess
- License
- Atribución 4.0 Internacional (CC BY 4.0)
id |
RCUC2_7836c0efeba92538f44c43b129127a02 |
---|---|
oai_identifier_str |
oai:repositorio.cuc.edu.co:11323/13363 |
network_acronym_str |
RCUC2 |
network_name_str |
REDICUC - Repositorio CUC |
repository_id_str |
|
dc.title.eng.fl_str_mv |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
title |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
spellingShingle |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City Alzheimer’s disease Biomarkers Dementia Genetics Hispanics Latin America |
title_short |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
title_full |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
title_fullStr |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
title_full_unstemmed |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
title_sort |
Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City |
dc.creator.fl_str_mv |
Sosa, Ana Luisa Brucki, Sonia MD Crivelli, Lucia Lopera, Francisco Javier Acosta, Daisy M Acosta-Uribe, Juliana Aguilar, Diego Aguilar-Navarro, Sara G Allegri, Ricardo F Bertolucci, Paulo HF Calandri, Ismael L Carrillo, Maria C Chrem Méndez, Patricio Alexis Cornejo-Olivas, Mario Custodio, Nilton Damian, Andrés Cruz de Souza, Leonardo Duran-Aniotz, Claudia García, Adolfo M García-Peña, Carmen Gonzales, Mitzi M Grinberg, Lea T Ibáñez, Agustín M Illanes-Manrique, Maryenela Zaida Jack Jr, Clifford R Leon-Salas, Jorge Mario Llibre-Guerra, Jorge J Luna-Muñoz, José Matallana, Diana Miller, Bruce L Naci, Lorina Parra, Mario A Pericak-Vance, Margaret Piña-Escudero, Stefanie D França Resende, Elisa de Paula Ringman, John M Sevlever, Gustavo Slachevsky, Andrea Kimie Suemoto, Claudia Valcour, Victor Villegas-Lanau, Andres Yassuda, Mônica S Mahinrad, Simin Sexton, Claire |
dc.contributor.author.none.fl_str_mv |
Sosa, Ana Luisa Brucki, Sonia MD Crivelli, Lucia Lopera, Francisco Javier Acosta, Daisy M Acosta-Uribe, Juliana Aguilar, Diego Aguilar-Navarro, Sara G Allegri, Ricardo F Bertolucci, Paulo HF Calandri, Ismael L Carrillo, Maria C Chrem Méndez, Patricio Alexis Cornejo-Olivas, Mario Custodio, Nilton Damian, Andrés Cruz de Souza, Leonardo Duran-Aniotz, Claudia García, Adolfo M García-Peña, Carmen Gonzales, Mitzi M Grinberg, Lea T Ibáñez, Agustín M Illanes-Manrique, Maryenela Zaida Jack Jr, Clifford R Leon-Salas, Jorge Mario Llibre-Guerra, Jorge J Luna-Muñoz, José Matallana, Diana Miller, Bruce L Naci, Lorina Parra, Mario A Pericak-Vance, Margaret Piña-Escudero, Stefanie D França Resende, Elisa de Paula Ringman, John M Sevlever, Gustavo Slachevsky, Andrea Kimie Suemoto, Claudia Valcour, Victor Villegas-Lanau, Andres Yassuda, Mônica S Mahinrad, Simin Sexton, Claire |
dc.subject.proposal.eng.fl_str_mv |
Alzheimer’s disease Biomarkers Dementia Genetics Hispanics Latin America |
topic |
Alzheimer’s disease Biomarkers Dementia Genetics Hispanics Latin America |
description |
While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm.Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care. |
publishDate |
2024 |
dc.date.accessioned.none.fl_str_mv |
2024-09-23T20:40:40Z |
dc.date.available.none.fl_str_mv |
2024-09-23T20:40:40Z |
dc.date.issued.none.fl_str_mv |
2024-05-27 |
dc.type.spa.fl_str_mv |
Artículo de revista |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.content.spa.fl_str_mv |
Text |
dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.redcol.spa.fl_str_mv |
http://purl.org/redcol/resource_type/ART |
dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
dc.identifier.citation.spa.fl_str_mv |
Sosa AL, Brucki SMD, Crivelli L, et al. Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer’s Association International conference satellite symposium in Mexico City. Alzheimer’s Dement. 2024;20:5009–5026. https://doi.org/10.1002/alz.13850 |
dc.identifier.issn.spa.fl_str_mv |
1552-5260 |
dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/11323/13363 |
dc.identifier.doi.none.fl_str_mv |
10.1002/alz.13850 |
dc.identifier.eissn.spa.fl_str_mv |
1552-5279 |
dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
identifier_str_mv |
Sosa AL, Brucki SMD, Crivelli L, et al. Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer’s Association International conference satellite symposium in Mexico City. Alzheimer’s Dement. 2024;20:5009–5026. https://doi.org/10.1002/alz.13850 1552-5260 10.1002/alz.13850 1552-5279 Corporación Universidad de la Costa REDICUC - Repositorio CUC |
url |
https://hdl.handle.net/11323/13363 https://repositorio.cuc.edu.co/ |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofjournal.spa.fl_str_mv |
Alzheimer's and Dementia |
dc.relation.references.spa.fl_str_mv |
1. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19:1598-1695. doi:10.1002/alz.13016 PMID:36918389 2. Dementia in Latin America and the Caribbean: Prevalence, Incidence, Impact, and Trends over Time. Pan American Health Organization; 2023. doi:10.37774/9789275126653 3. Prince M, Acosta D, Ferri CP, et al. Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study. Lancet Lond Engl. 2012;380:50-58. doi:10.1016/S0140- 6736(12)60399-7 4. Ibáñez A, Pina-Escudero SD, Possin KL, et al. Dementia caregiving across Latin America and the Caribbean and brain health diplomacy. Lancet Healthy Longev. 2021;2:e222-e231. doi:10.1016/ S2666-7568(21)00031-3 5. Parra MA, Baez S, Sedeño L, et al. Dementia in Latin America: paving the way toward a regional action plan. Alzheimers Dement J Alzheimers Assoc. 2021;17:295-313. doi:10.1002/alz.12202 6. Matsuda Y, Brooks JL, Beeber LS. Guidelines for research recruitment of underserved populations (EERC). Appl Nurs Res ANR. 2016;32:164-170. doi:10.1016/j.apnr.2016.07.009 7. Marquez DX, Perez A, Johnson JK, et al. Increasing engagement of Hispanics/Latinos in clinical trials on Alzheimer’s disease and related dementias. Alzheimers Dement N Y N. 2022;8:e12331. doi:10.1002/ trc2.12331 8. Demographic Observatory. Latin America and the Caribbean 2022. Population trends in Latin America and the Caribbean: demographic effects of the COVID-19 pandemic. Popul Trends. 2022. 9. Rodriguez JJL, Ferri CP, Acosta D, Guerra M, Huang Y, Jacob K, et al. Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey. The Lancet. 2008;372:464- 474. doi:10.1016/S0140-6736(08)61002-8 10. Prince M, Ferri CP, Acosta D, Albanese E, Arizaga R, Dewey M, et al. The protocols for the 10/66 dementia research group populationbased research programme. BMC Public Health. 2007;7:165. doi:10. 1186/1471-2458-7-165 11. Ribeiro F, Teixeira-Santos AC, Caramelli P, Leist AK. Prevalence of dementia in Latin America and Caribbean countries: systematic review and meta-analyses exploring age, sex, rurality, and education as possible determinants. Ageing Res Rev. 2022;81:101703. doi:10. 1016/j.arr.2022.101703 12. Nitrini R, Caramelli P, Herrera E, Bahia VS, Caixeta LF, Radanovic M, et al. Incidence of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord. 2004;18:241- 246. 13. Lopes MA, Nassar SM, Barcelos-Ferreira R, Folquitto JC, Litvoc J. Incidence of dementia in a population cohort of older people from São Paulo, Brazil. Int J Geriatr Psychiatry. 2022;37:gps.5660. doi:10.1002/ gps.5660 14. César-Freitas KG, Suemoto CK, Power MC, Brucki SMD, Nitrini R. Incidence of dementia in a Brazilian population: the Tremembé Epidemiologic Study. Alzheimers Dement J Alzheimers Assoc. 2022;18:581-590. doi:10.1002/alz.12423 15. Sousa RM, Ferri CP, Acosta D, et al. The contribution of chronic diseases to the prevalence of dependence among older people in Latin America, China and India: a 10/66 Dementia Research Group population-based survey. BMC Geriatr. 2010;10:53. doi:10.1186/ 1471-2318-10-53 16. World Health Organization. Global action plan on the public health response to dementia 2017-2025. World Health Organization; 2017. 17. World Health Organization. Global status report on the public health response to dementia. World Health Organization; 2021. 18. Custodio N,Wheelock A, Thumala D, Slachevsky A. Dementia in Latin America: epidemiological Evidence and Implications for Public Policy. Front Aging Neurosci. 2017;9:221. doi:10.3389/fnagi.2017.00221 19. Scearce-Levie K, Sanchez PE, Lewcock JW. Leveraging preclinical models for the development of Alzheimer disease therapeutics. Nat Rev Drug Discov. 2020;19:447-462. doi:10.1038/s41573-020-0065- 9 20. Sirugo G, Williams SM, Tishkoff SA. The Missing Diversity in Human Genetic Studies. Cell. 2019;177:26-31. doi:10.1016/j.cell.2019.02. 048 21. Kunkle BW, Grenier-Boley B, Sims R, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet. 2019;51:414-430. doi:10.1038/s41588-019-0358-2 22. Ryman DC, Acosta-Baena N, Aisen PS, et al. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014;83:253-260. doi:10.1212/WNL. 0000000000000596 23. Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77:43-51. doi:10. 1016/j.biopsych.2014.05.006 24. Llibre-Guerra JJ, Li Y, Allegri RF, et al. Dominantly inherited Alzheimer’s disease in Latin America: genetic heterogeneity and clinical phenotypes. Alzheimers Dement J Alzheimers Assoc. 2021;17:653- 664. doi:10.1002/alz.12227 25. Lopera F, Ardilla A, Martínez A, et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA. 1997;277:793-799. 26. Athan ES, Williamson J, Ciappa A, et al. A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. JAMA. 2001;286:2257-2263. doi:10.1001/jama. 286.18.2257 27. Yescas P, Huertas-Vazquez A, Villarreal-Molina MT, et al. Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer’s disease in Mexican families. Neurogenetics. 2006;7:195-200. doi:10.1007/s10048-006-0043-3 28. Murrell J, Ghetti B, Cochran E, et al. The A431E mutation in PSEN1 causing familial Alzheimer’s disease originating in Jalisco State, Mexico: an additional fifteen families. Neurogenetics. 2006;7:277-279. doi:10.1007/s10048-006-0053-1 29. Dumois-Petersen S, Gallegos-ArreolaMP,Magaña-TorresMT, PereaDíaz FJ, Ringman JM, Figuera LE. Autosomal dominant early onset Alzheimer’s disease in the Mexican state of Jalisco: high frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients. Am J Med Genet C Semin Med Genet. 2020;184:1023-1029. doi:10. 1002/ajmg.c.31865 30. Soosman SK, Joseph-Mathurin N, Braskie MN, et al. Widespread white matter and conduction defects in PSEN1-related spastic paraparesis. Neurobiol Aging. 2016;47:201-209. doi:10.1016/j. neurobiolaging.2016.07.030 31. Lalli MA, Cox HC, Arcila ML, et al. Origin of the PSEN1 E280A mutation causing early-onset Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2014;10:S277-S283.e10. doi:10.1016/j.jalz.2013. 09.005 32. Sepulveda-Falla D, Glatzel M, Lopera F. Phenotypic profile of earlyonset familial Alzheimer’s disease caused by presenilin-1 E280A mutation. J Alzheimers Dis JAD. 2012;32:1-12. doi:10.3233/JAD2012-120907 33. Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, et al. Predementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol. 2011;10:213-220. doi:10.1016/S1474-4422(10)70323-9 34. Cochran JN, Acosta-Uribe J, Esposito BT, et al. Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred. Alzheimers Dement J Alzheimers Assoc. 2023;19(9):3835-3847. doi:10. 1002/alz.13021 35. Arboleda-Velasquez JF, Lopera F, O’Hare M, et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25:1680-1683. doi:10. 1038/s41591-019-0611-3 36. Lopera F, Marino C, Chandrahas AS, et al. Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man. Nat Med. 2023;29:1243-1252. doi:10.1038/s41591-023- 02318-3 37. Bateman RJ, Xiong C, Benzinger TLS, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795-804. doi:10.1056/NEJMoa1202753 38. Moulder KL, Snider BJ, Mills SL, et al. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther. 2013;5:48. doi:10.1186/alzrt213 39. Takada LT, Aláez-Verson C, Burgute BD, et al. Discovery and validation of dominantly inherited Alzheimer’s disease mutations in populations from Latin America. Alzheimers Res Ther. 2022;14:108. doi:10.1186/s13195-022-01052-1 40. Bateman RJ, Benzinger TL, Berry S, et al. The DIAN-TU Next Generation Alzheimer’s prevention trial: adaptive design and disease progression model. Alzheimers Dement J Alzheimers Assoc. 2017;13:8-19. doi:10.1016/j.jalz.2016.07.005 41. Acosta-Uribe J, Aguillón D, Cochran JN, et al. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects. Genome Med. 2022;14:27. doi:10.1186/s13073-022-01035- 9 42. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921-923. doi:10.1126/science. 8346443 43. Reitz C, Jun G, Naj A, et al. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013;309:1483- 1492. doi:10.1001/jama.2013.2973 44. Choi KY, Lee JJ, Gunasekaran TI, et al. APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer’s Disease Risk in a Multiracial Sample. J Clin Med. 2019;8:1236. doi:10.3390/jcm8081236 45. Hendrie HC, Murrell J, Baiyewu O, et al. APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba. Int Psychogeriatr. 2014;26:977-985. doi:10.1017/ S1041610214000167 46. Rajabli F, Feliciano BE, Celis K, et al. Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. PLOS Genet. 2018;14:e1007791. doi:10.1371/journal.pgen. 1007791 47. Granot-Hershkovitz E, Tarraf W, Kurniansyah N, et al. APOE alleles’ association with cognitive function differs across Hispanic/Latino groups and genetic ancestry in the study of Latinos-investigation of neurocognitive aging (HCHS/SOL). Alzheimers Dement J Alzheimers Assoc. 2021;17:466-474. doi:10.1002/alz.12205 48. Llibre-Guerra JJ, Li Y, Allen IE, et al. Race, Genetic Admixture, and Cognitive Performance in the Cuban Population. J Gerontol Ser A. 2022;77:331-338. doi:10.1093/gerona/glab063 49. Llibre-Guerra JJ, Li J, Qian Y, et al. Apolipoprotein E (APOE) genotype, dementia, and memory performance among Caribbean Hispanic versus US populations. Alzheimers Dement. 2023;19:602-610. doi:10. 1002/alz.12699 50. Marca-Ysabel MV, Rajabli F, Cornejo-Olivas M, et al. Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population. Neurobiol Aging. 2021;101:298.e11-298.e15. doi:10.1016/j.neurobiolaging.2020.10.003 51. Naslavsky MS, Suemoto CK, Brito LA, et al. Global and local ancestry modulate APOE association with Alzheimer’s neuropathology and cognitive outcomes in an admixed sample. Mol Psychiatry. 2022;27:4800-4808. doi:10.1038/s41380-022-01729-x 52. Blue EE, Horimoto ARVR, Mukherjee S, Wijsman EM, Thornton TA. Local ancestry at APOE modifies Alzheimer’s disease risk in Caribbean Hispanics. Alzheimers Dement. 2019;15:1524-1532. doi:10.1016/j.jalz.2019.07.016 53. Griswold AJ, Celis K, Bussies PL, et al. Increased APOE ε4 expression is associated with the difference in Alzheimer’s disease risk from diverse ancestral backgrounds. Alzheimers Dement. 2021;17:1179- 1188. doi:10.1002/alz.12287 54. McKhann GM, Knopman DS, Chertkow H, et al. 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 J Alzheimers Assoc. 2011;7:263-269. doi:10.1016/j.jalz.2011.03. 005 55. Sperling RA, Aisen PS, Beckett LA, et al. Toward 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 J Alzheimers Assoc. 2011;7:280-292. doi:10.1016/j.jalz.2011.03.003 56. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment 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 J Alzheimers Assoc. 2011;7:270-279. doi:10.1016/j.jalz.2011.03.008 57. Parra MA, Orellana P, Leon T, et al. Biomarkers for dementia in Latin American countries: gaps and opportunities. Alzheimers Dement J Alzheimers Assoc. 2023;19:721-735. doi:10.1002/alz.12757 58. Gustavo Cuña E, Schulz H, Tuzzi E, et al. Simulated and experimental phantom data for multi-center quality assurance of quantitative susceptibility maps at 3 T, 7 T and 9.4 T. Phys Medica PM Int J Devoted Appl Phys Med Biol Off J Ital Assoc Biomed Phys AIFB. 2023;110:102590. doi:10.1016/j.ejmp.2023.102590 59. Moguilner S, Whelan R, Adams H, Valcour V, Tagliazucchi E, Ibáñez A. Visual deep learning of unprocessed neuroimaging characterises dementia subtypes and generalises across non-stereotypic samples. eBioMedicine. 2023;90:104540. doi:10.1016/j.ebiom.2023.104540 60. Russo MJ, Gustafson D, Vázquez S, et al. Creation of the ArgentinaAlzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement J Alzheimers Assoc. 2014;10:S84-S87. doi:10.1016/j.jalz.2013.09.015 61. Allegri RF, Pertierra L, Cohen G, et al. A biological classification for Alzheimer’s disease—Amyloid, Tau and Neurodegeneration (A/T/N): results from the Argentine-Alzheimer’s Disease Neuroimaging Initiative. Int Psychogeriatr. 2019;31:1837-1838. doi:10.1017/ S1041610219000085 62. Allegri RF, Chrem Méndez P, Calandri I, et al. Prognostic value of ATN Alzheimer biomarkers: 60-month follow-up results from the Argentine Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement Amst Neth. 2020;12:e12026. doi:10.1002/dad2.12026 63. Patricio CM, Gabriela C, Julieta RM, et al. Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic. Am J Alzheimers Dis Other Demen. 2015;30:599-606. doi:10.1177/1533317515576387 64. Lopera F, Custodio N, Rico-Restrepo M, et al. A task force for diagnosis and treatment of people with Alzheimer’s disease in Latin America. Front Neurol. 2023;14:1198869. doi:10.3389/fneur.2023. 1198869 65. Carneiro CDG, Faria DDP, Coutinho AM, et al. Evaluation of 10- minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer’s disease. Braz J Psychiatry. 2022;44(5):495- 506. doi:10.47626/1516-4446-2021-2374 66. Hansson O, Edelmayer RM, Boxer AL, et al. The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2022;18:2669-2686. doi:10.1002/alz.12756 67. Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93:e1647-e1659. doi:10.1212/WNL. 0000000000008081 68. Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19:422-433. doi:10.1016/ S1474-4422(20)30071-5 69. Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2019;76:791-799. doi:10.1001/jamaneurol.2019.0765 70. Verberk IMW, Thijssen E, Koelewijn J, et al. Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimers Res Ther. 2020;12:118. doi:10.1186/s13195-020-00682-7 71. Steinacker P, Anderl-Straub S, Diehl-Schmid J, et al. Serum neurofilament light chain in behavioral variant frontotemporal dementia. Neurology. 2018;91:e1390-e1401. doi:10.1212/WNL. 0000000000006318 72. Chouliaras L, Thomas A, Malpetti M, et al. Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2022;93:651-658. doi:10.1136/jnnp-2021-327788 73. Duran-Aniotz C, Orellana P, Leon Rodriguez T, et al. Systematic Review: genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries. Front Neurol. 2021;12:663407. doi:10.3389/fneur.2021.663407 74. García AM, DeLeon J, Tee BL. Neurodegenerative Disorders of Speech and Language: non-language-dominant Diseases. Encycl Behav Neurosci. 2022:66-80. 2nd Ed., Elsevier. doi:10.1016/B978-0- 12-819641-0.00042-6 75. Sanz C, Carrillo F, Slachevsky A, et al. Automated text-level semantic markers of Alzheimer’s disease. Alzheimers Dement Diagn Assess Dis Monit. 2022;14:e12276. doi:10.1002/dad2.12276 76. Ferrante FJ, Migeot J, Birba A, et al. Multivariate word properties in fluency tasks reveal markers of Alzheimer’s dementia. Alzheimers Dement J Alzheimers Assoc. 2023;20(2):925-940. doi:10.1002/alz. 13472 77. García AM, Arias-Vergara T, Vasquez-Correa JC, et al. Cognitive Determinants of Dysarthria in Parkinson’s Disease: an AutomatedMachine Learning Approach. Mov Disord. 2021;36:2862-2873. doi:10.1002/mds.28751 78. García AM, Escobar-Grisales D, Vásquez Correa JC, et al. Detecting Parkinson’s disease and its cognitive phenotypes via automated semantic analyses of action stories. Npj Park Dis. 2022;8:163. doi:10. 1038/s41531-022-00422-8 79. Sanz C, Carrillo F, Slachevsky A, et al. Automated text-level semantic markers of Alzheimer’s disease. Alzheimers Dement Amst Neth. 2022;14:e12276. doi:10.1002/dad2.12276 80. García AM, Johann F, Echegoyen R, et al. Toolkit to Examine Lifelike Language (TELL): an app to capture speech and language markers of neurodegeneration. Behav Res Methods. 2023. doi:10.3758/s13428- 023-02240-z 81. García AM, De Leon J, Tee BL, Blasi DE, Gorno-Tempini ML. Speech and language markers of neurodegeneration: a call for global equity. Brain. 2023;146(12):4870-4879. doi:10.1093/brain/ awad253. awad253. 82. Kretzschmar H. Brain banking: opportunities, challenges and meaning for the future. Nat Rev Neurosci. 2009;10:70-78. doi:10.1038/ nrn2535 83. Grinberg LT, Ferretti RE de L, Farfel JM, et al. Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains. Cell Tissue Bank. 2007;8:151-162. doi:10. 1007/s10561-006-9022-z 84. Suemoto CK, Ferretti-Rebustini REL, Rodriguez RD, et al. Neuropathological diagnoses and clinical correlates in older adults in Brazil: a cross-sectional study. PLoS Med. 2017;14:e1002267. doi:10. 1371/journal.pmed.1002267 85. Grinberg LT, Nitrini R, Suemoto CK, et al. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clin Sao Paulo Braz. 2013;68:1140-1145. doi:10.6061/clinics/2013(08)13 86. Schlesinger D, Grinberg LT, Alba JG, et al. African ancestry protects against Alzheimer’s disease-related neuropathology. Mol Psychiatry. 2013;18:79-85. doi:10.1038/mp.2011.136 87. Taratuto AL, Piccardo P, Leiguarda R, et al. Creutzfeldt-Jakob disease. Report of 10 neuropathologically-verified cases in Argentina. Medicina (Mex). 1989;49:293-303. 88. Riudavets MA, Sraka MA, Schultz M, et al. Gerstmann-SträusslerScheinker syndrome with variable phenotype in a new kindred with PRNP-P102L mutation. Brain Pathol Zurich Switz. 2014;24:142-147. doi:10.1111/bpa.12083 89. Taratuto AL, Piccardo P, Reich EG, et al. Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease.Neurology. 2002;58:362-367. doi:10.1212/wnl.58.3.362 90. Allegri RF, Bartoloni L, IturryM, et al.MM1+2C sporadic CreutzfeldtJakob disease presenting as rapidly progressive nonfluent aphasia. J Alzheimers Dis JAD. 2014;39:13-17. doi:10.3233/JAD-130350 91. Riudavets MA, Bartoloni L, Troncoso JC, et al. Familial dementia with frontotemporal features associated with M146V presenilin-1 mutation. Brain Pathol Zurich Switz. 2013;23:595-600. doi:10.1111/bpa. 12051 92. Littau JL, Velilla L, Hase Y, et al. Evidence of beta amyloid independent small vessel disease in familial Alzheimer’s disease. Brain Pathol Zurich Switz. 2022;32:e13097. doi:10.1111/bpa.13097 93. Soto-Ospina A, Araque Marín P, Bedoya GJ, Villegas Lanau A. Structural Predictive Model of Presenilin-2 Protein and Analysis of Structural Effects of Familial Alzheimer’s DiseaseMutations.Biochem Res Int. 2021;2021:9542038. doi:10.1155/2021/9542038 94. Sepulveda-Falla D, Sanchez JS, Almeida MC, et al. Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia. Acta Neuropathol (Berl). 2022;144:589-601. doi:10.1007/s00401- 022-02467-8 95. Vélez JI, Lopera F, Silva CT, et al. Familial Alzheimer’s Disease and Recessive Modifiers. Mol Neurobiol. 2020;57:1035-1043. doi:10. 1007/s12035-019-01798-0 96. Reyes-Pablo AE, Campa-Córdoba BB, Luna-Viramontes NI, et al. National Dementia BioBank: a Strategy for the Diagnosis and Study of Neurodegenerative Diseases in México. J Alzheimers Dis. 2020;76:853-862. doi:10.3233/JAD-191015 97. mdorsey. First-of-its-Kind DNA Biobank Opens in Peru. Aligning Sci Park 2021. accessed October 19, 2023. https://parkinsonsroadmap.org/ news/first-of-its-kind-dna-biobank-opens-in-peru 98. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396:413-446. doi:10.1016/S0140-6736(20)30367-6 99. Mukadam N, Sommerlad A, Huntley J, Livingston G. Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. Lancet Glob Health. 2019;7:e596-603. doi:10.1016/S2214- 109X(19)30074-9 100. Suemoto CK, Bertola L, Grinberg LT, et al. Education, but not occupation, is associated with cognitive impairment: the role of cognitive reserve in a sample from a low-to-middle-income country. Alzheimers Dement J Alzheimers Assoc. 2022;18:2079-2087. doi:10.1002/alz. 12542 101. Santamaria-Garcia H, Sainz-Ballesteros A, Hernandez H, et al. Factors associated with healthy aging in Latin American populations.Nat Med. 2023;29:2248-2258. doi:10.1038/s41591-023-02495-1 102. Risk factors related to population diversity and disparity determine healthy aging. Nat Med. 2023;29:2183-2184. doi:10.1038/s41591- 023-02531-0 103. Nitrini R, Bottino CMC, Albala C, et al. Prevalence of dementia in Latin America: a collaborative study of population-based cohorts. Int Psychogeriatr. 2009;21:622-630. doi:10.1017/S1041610209009430 104. Herrera-Perez E, Custodio N, Diaz M, et al. Epidemiology of neurocognitive disorders in adults from urban-marginalized areas: a door-to-door population-based study in Puente Piedra, Lima, Peru. Front Public Health. 2023;11:1228008. doi:10.3389/fpubh.2023. 1228008 105. Resende E de PF, Tovar-Moll FF, Ferreira FM, et al. White Matter Microstructure in Illiterate and Low-Literate Elderly Brazilians: preliminary Findings. Cogn Behav Neurol Off J Soc Behav Cogn Neurol. 2018;31:193-200. doi:10.1097/WNN.0000000000000173 106. De Resende EDPF, Xia F, Sidney S, et al. Higher literacy is associated with better white matter integrity and cognition in middle age. Alzheimers Dement Diagn Assess Dis Monit. 2022;14:e12363. doi:10. 1002/dad2.12363 107. Resende E de PF, Rosen HJ, Chiang K, et al. Primary School Education May Be Sufficient toModerate aMemory-Hippocampal Relationship. Front Aging Neurosci. 2018;10:381. doi:10.3389/fnagi.2018.00381 108. O’Shea DM, Langer K, Woods AJ, et al. Educational Attainment Moderates the Association Between Hippocampal Volumes and Memory Performances in Healthy Older Adults. Front Aging Neurosci. 2018;10:361. doi:10.3389/fnagi.2018.00361 109. Kalaria RN, Maestre GE, Arizaga R, et al. Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 2008;7:812-826. doi:10.1016/S1474- 4422(08)70169-8 110. Suemoto CK, Szlejf C, Santos IS, et al. Ideal vascular health and cognitive performance in the Brazilian Longitudinal Study of Adult Health. Eur J Neurol. 2021;28:71-80. doi:10.1111/ene.14532 111. Suemoto CK, Mukadam N, Brucki SMD, et al. Risk factors for dementia in Brazil: differences by region and race. Alzheimers Dement. 2023;19:1849-1857. doi:10.1002/alz.12820 112. Vergara RC, Zitko P, Slachevsky A, San Martin C, Delgado C. Population attributable fraction of modifiable risk factors for dementia in Chile. Alzheimers Dement Amst Neth. 2022;14:e12273. doi:10.1002/ dad2.12273 113. Henríquez F, Cabello V, Baez S, et al. Multidimensional Clinical Assessment in Frontotemporal Dementia and Its Spectrum in Latin America and the Caribbean: a Narrative Review and a Glance at Future Challenges. Front Neurol. 2022;12:768591. doi:10.3389/ fneur.2021.768591 114. REDONE.br – Neuroimmunology Brazilian Study Group Focused on COVID-19 and MS. Incidence and clinical outcome of Coronavirus disease 2019 in a cohort of 11,560 Brazilian patients with multiple sclerosis. Mult Scler Houndmills Basingstoke Engl. 2021;27:1615-1619. doi:10.1177/1352458520978354 115. Crivelli L, Calandri IL, Suemoto CK, et al. Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAmFINGERS): study design and harmonization. Alzheimers Dement J Alzheimers Assoc. 2023;19(9):4046-4060. doi:10.1002/alz.13101 116. Maito MA, Santamaría-García H, Moguilner S, et al. Classification of Alzheimer’s disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: a cross sectional observational study. Lancet Reg Health— Am. 2023;17:100387. doi:10.1016/j.lana.2022.100387 117. Sanz Perl Y, Fittipaldi S, Gonzalez Campo C, et al. Model-based whole-brain perturbational landscape of neurodegenerative diseases. eLife. 2023;12:e83970. doi:10.7554/eLife.83970 118. Santamaria-Garcia H, Moguilner S, Rodriguez-Villagra OA, et al. The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations. GeroScience. 2023;45(4):2405-2423. doi:10.1007/s11357- 023-00755-z 119. Ibáñez A, Legaz A, Ruiz-Adame M. Addressing the gaps between socioeconomic disparities and biological models of dementia. Brain. 2023;146:3561-3564. doi:10.1093/brain/awad236 120. Ibanez A, Parra MA, Butler C. Latin America and the Caribbean Consortium on Dementia (LAC-CD). The Latin America and the Caribbean Consortium on Dementia (LAC-CD): from Networking to Research to Implementation Science. J Alzheimers Dis JAD. 2021;82:S379-S394. doi:10.3233/JAD-201384 121. Ibanez A, Yokoyama JS, Possin KL, et al. The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): driving Multicentric Research and Implementation Science. Front Neurol. 2021;12:631722. doi:10.3389/fneur.2021.631722 122. Slachevsky A, Zitko P, Martínez-Pernía D, et al. GERO Cohort Protocol, Chile, 2017-2022: community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly. BMC Geriatr. 2020;20:505. doi:10.1186/s12877-020-01866-4 123. Santamaría-García H, Ogonowsky N, Baez S, et al. Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study. BMC Neurol. 2022;22:454. doi:10.1186/s12883-022-02954-1 124. Migeot J, Calivar M, Granchetti H, Ibáñez A, Fittipaldi S. Socioeconomic status impacts cognitive and socioemotional processes in healthy ageing. Sci Rep. 2022;12:6048. doi:10.1038/s41598-022- 09580-4 125. De Felice FG, Gonçalves RA, Ferreira ST. Impaired insulin signalling and allostatic load in Alzheimer disease. Nat Rev Neurosci. 2022;23:215-230. doi:10.1038/s41583-022-00558-9 126. Migeot JA, Duran-Aniotz CA, Signorelli CM, Piguet O, Ibáñez A. A predictive coding framework of allostatic-interoceptive overload in frontotemporal dementia. Trends Neurosci. 2022;45:838-853. doi:10. 1016/j.tins.2022.08.005 127. Crivelli L. LatAm-FINGERS (Latin America): world-Wide FINGERS network: the first global network of multidomain dementia prevention trials. Alzheimers Dement. 2020;16. doi:10.1002/alz.046953 128. Kivipelto M, Solomon A, Ahtiluoto S, et al. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 2013;9:657- 665. doi:10.1016/j.jalz.2012.09.012 129. Allegri RF, Bagnati P, Brucki S, Nitrini R. South America’s AD Clinical Trials Experience. Glob Clin Trials Alzheimers Dis. 2014:219-230. doi:10.1016/B978-0-12-411464-7.00013-4. Elsevier. 130. Llibre-Guerra JJ, Heavener A, Brucki SMD, et al. A call for clinical trial globalization in Alzheimer’s disease and related dementia. Alzheimers Dement J Alzheimers Assoc. 2023;19:3210-3221. doi:10. 1002/alz.12995 131. Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement Transl Res Clin Interv. 2023;9:e12385. doi:10.1002/trc2.12385 132. de Miranda LFJR, Matoso R de O, Rodrigues MV, et al. Factors influencing possible delay in the diagnosis of Alzheimer’s disease: findings from a tertiary Public University Hospital. Dement Neuropsychol. 2011;5:328-331. doi:10.1590/S1980-57642011DN05040011 133. Chávez-Fumagalli MA, Shrivastava P, Aguilar-Pineda JA, et al. Diagnosis of Alzheimer’s Disease in Developed and Developing Countries: systematic Review and Meta-Analysis of Diagnostic Test Accuracy. J Alzheimers Dis Rep. 2021;5:15-30. doi:10.3233/ADR-200263 134. Mills SM, Mallmann J, Santacruz AM, et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013;169:737-743. doi:10.1016/j.neurol.2013.07.017 135. Joseph-Mathurin N, Llibre-Guerra JJ, Li Y, et al. Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: lessons from a Trial in Dominantly Inherited Alzheimer Disease. Ann Neurol. 2022;92:729-744. doi:10.1002/ana. 26511 136. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med. 2023;388:9-21. doi:10.1056/ NEJMoa2212948 137. Roberts M, Sevastou I, Imaizumi Y, et al. Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease. Acta Neuropathol Commun. 2020;8:13. doi:10.1186/s40478- 020-0884-2 138. Rios-Romenets S, Lopera F, Sink KM, et al. Baseline demographic, clinical, and cognitive characteristics of the Alzheimer’s Prevention Initiative (API) Autosomal-Dominant Alzheimer’s Disease Colombia Trial. Alzheimers Dement J Alzheimers Assoc. 2020;16:1023-1030. doi:10.1002/alz.12109 139. Ltd FH-LR. Roche provides update on Alzheimer’s Prevention Initiative study evaluating crenezumab in autosomal dominant Alzheimer’s disease. GlobeNewswire News Room 2022. (accessed August 31, 2023). https://www.globenewswire.com/newsrelease/2022/06/16/2463591/0/en/Roche-provides-update-onAlzheimer-s-Prevention-Initiative-study-evaluating-crenezumabin-autosomal-dominant-Alzheimer-s-disease.html 140. SA AI. Detailed Data From the Phase II Crenezumab Alzheimer’s Prevention Initiative Study in Autosomal Dominant Alzheimer’s Disease Presented at AAIC. GlobeNewswire News Room 2022. Accessed August 31, 2023. https://www.globenewswire.com/newsrelease/2022/08/02/2490659/0/en/Detailed-Data-From-thePhase-II-Crenezumab-Alzheimer-s-Prevention-Initiative-Studyin-Autosomal-Dominant-Alzheimer-s-Disease-Presented-atAAIC.html. |
dc.relation.citationendpage.spa.fl_str_mv |
5026 |
dc.relation.citationstartpage.spa.fl_str_mv |
5009 |
dc.relation.citationissue.spa.fl_str_mv |
7 |
dc.relation.citationvolume.spa.fl_str_mv |
20 |
dc.rights.license.spa.fl_str_mv |
Atribución 4.0 Internacional (CC BY 4.0) |
dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
rights_invalid_str_mv |
Atribución 4.0 Internacional (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ http://purl.org/coar/access_right/c_abf2 |
eu_rights_str_mv |
openAccess |
dc.format.extent.spa.fl_str_mv |
18 páginas |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.coverage.city.none.fl_str_mv |
Mexico City |
dc.coverage.region.none.fl_str_mv |
Latin America |
dc.publisher.spa.fl_str_mv |
John Wiley & Sons Inc. |
dc.publisher.place.spa.fl_str_mv |
United States |
dc.source.spa.fl_str_mv |
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13850 |
institution |
Corporación Universidad de la Costa |
bitstream.url.fl_str_mv |
https://repositorio.cuc.edu.co/bitstreams/0f522f12-b80a-439e-86f1-2cd5bbad0b4c/download https://repositorio.cuc.edu.co/bitstreams/cbd3d760-cd7c-4c24-88b2-e5fa392e4258/download https://repositorio.cuc.edu.co/bitstreams/a742d2d0-0918-4200-8f4b-993e041716e8/download https://repositorio.cuc.edu.co/bitstreams/ac2ae389-e310-4372-800f-130705514742/download |
bitstream.checksum.fl_str_mv |
d0ae1872fc44cdfd10d22af66d7f105b 2f9959eaf5b71fae44bbf9ec84150c7a 1a470db71b16585340cf795737c40fe3 b9bd98a766359b11eb1d91d195f102a0 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio de la Universidad de la Costa CUC |
repository.mail.fl_str_mv |
repdigital@cuc.edu.co |
_version_ |
1811760855289692160 |
spelling |
Atribución 4.0 Internacional (CC BY 4.0)© 2024 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Sosa, Ana LuisaBrucki, Sonia MDCrivelli, LuciaLopera, Francisco JavierAcosta, Daisy MAcosta-Uribe, JulianaAguilar, DiegoAguilar-Navarro, Sara GAllegri, Ricardo FBertolucci, Paulo HFCalandri, Ismael LCarrillo, Maria CChrem Méndez, Patricio AlexisCornejo-Olivas, MarioCustodio, NiltonDamian, AndrésCruz de Souza, LeonardoDuran-Aniotz, ClaudiaGarcía, Adolfo MGarcía-Peña, CarmenGonzales, Mitzi MGrinberg, Lea TIbáñez, Agustín MIllanes-Manrique, Maryenela ZaidaJack Jr, Clifford RLeon-Salas, Jorge MarioLlibre-Guerra, Jorge JLuna-Muñoz, JoséMatallana, DianaMiller, Bruce LNaci, LorinaParra, Mario APericak-Vance, MargaretPiña-Escudero, Stefanie DFrança Resende, Elisa de PaulaRingman, John MSevlever, GustavoSlachevsky, AndreaKimie Suemoto, ClaudiaValcour, VictorVillegas-Lanau, AndresYassuda, Mônica SMahinrad, SiminSexton, Claire2024-09-23T20:40:40Z2024-09-23T20:40:40Z2024-05-27Sosa AL, Brucki SMD, Crivelli L, et al. Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer’s Association International conference satellite symposium in Mexico City. Alzheimer’s Dement. 2024;20:5009–5026. https://doi.org/10.1002/alz.138501552-5260https://hdl.handle.net/11323/1336310.1002/alz.138501552-5279Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm.Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.18 páginasapplication/pdfengJohn Wiley & Sons Inc.United Stateshttps://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13850Advancements in dementia research, diagnostics, and care in Latin America: highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico CityArtículo 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_970fb48d4fbd8a85Mexico CityLatin AmericaAlzheimer's and Dementia1. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023;19:1598-1695. doi:10.1002/alz.13016 PMID:369183892. Dementia in Latin America and the Caribbean: Prevalence, Incidence, Impact, and Trends over Time. Pan American Health Organization; 2023. doi:10.37774/97892751266533. Prince M, Acosta D, Ferri CP, et al. Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study. Lancet Lond Engl. 2012;380:50-58. doi:10.1016/S0140- 6736(12)60399-74. Ibáñez A, Pina-Escudero SD, Possin KL, et al. Dementia caregiving across Latin America and the Caribbean and brain health diplomacy. Lancet Healthy Longev. 2021;2:e222-e231. doi:10.1016/ S2666-7568(21)00031-35. Parra MA, Baez S, Sedeño L, et al. Dementia in Latin America: paving the way toward a regional action plan. Alzheimers Dement J Alzheimers Assoc. 2021;17:295-313. doi:10.1002/alz.122026. Matsuda Y, Brooks JL, Beeber LS. Guidelines for research recruitment of underserved populations (EERC). Appl Nurs Res ANR. 2016;32:164-170. doi:10.1016/j.apnr.2016.07.0097. Marquez DX, Perez A, Johnson JK, et al. Increasing engagement of Hispanics/Latinos in clinical trials on Alzheimer’s disease and related dementias. Alzheimers Dement N Y N. 2022;8:e12331. doi:10.1002/ trc2.123318. Demographic Observatory. Latin America and the Caribbean 2022. Population trends in Latin America and the Caribbean: demographic effects of the COVID-19 pandemic. Popul Trends. 2022.9. Rodriguez JJL, Ferri CP, Acosta D, Guerra M, Huang Y, Jacob K, et al. Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey. The Lancet. 2008;372:464- 474. doi:10.1016/S0140-6736(08)61002-810. Prince M, Ferri CP, Acosta D, Albanese E, Arizaga R, Dewey M, et al. The protocols for the 10/66 dementia research group populationbased research programme. BMC Public Health. 2007;7:165. doi:10. 1186/1471-2458-7-16511. Ribeiro F, Teixeira-Santos AC, Caramelli P, Leist AK. Prevalence of dementia in Latin America and Caribbean countries: systematic review and meta-analyses exploring age, sex, rurality, and education as possible determinants. Ageing Res Rev. 2022;81:101703. doi:10. 1016/j.arr.2022.10170312. Nitrini R, Caramelli P, Herrera E, Bahia VS, Caixeta LF, Radanovic M, et al. Incidence of dementia in a community-dwelling Brazilian population. Alzheimer Dis Assoc Disord. 2004;18:241- 246.13. Lopes MA, Nassar SM, Barcelos-Ferreira R, Folquitto JC, Litvoc J. Incidence of dementia in a population cohort of older people from São Paulo, Brazil. Int J Geriatr Psychiatry. 2022;37:gps.5660. doi:10.1002/ gps.566014. César-Freitas KG, Suemoto CK, Power MC, Brucki SMD, Nitrini R. Incidence of dementia in a Brazilian population: the Tremembé Epidemiologic Study. Alzheimers Dement J Alzheimers Assoc. 2022;18:581-590. doi:10.1002/alz.1242315. Sousa RM, Ferri CP, Acosta D, et al. The contribution of chronic diseases to the prevalence of dependence among older people in Latin America, China and India: a 10/66 Dementia Research Group population-based survey. BMC Geriatr. 2010;10:53. doi:10.1186/ 1471-2318-10-5316. World Health Organization. Global action plan on the public health response to dementia 2017-2025. World Health Organization; 2017.17. World Health Organization. Global status report on the public health response to dementia. World Health Organization; 2021.18. Custodio N,Wheelock A, Thumala D, Slachevsky A. Dementia in Latin America: epidemiological Evidence and Implications for Public Policy. Front Aging Neurosci. 2017;9:221. doi:10.3389/fnagi.2017.0022119. Scearce-Levie K, Sanchez PE, Lewcock JW. Leveraging preclinical models for the development of Alzheimer disease therapeutics. Nat Rev Drug Discov. 2020;19:447-462. doi:10.1038/s41573-020-0065- 920. Sirugo G, Williams SM, Tishkoff SA. The Missing Diversity in Human Genetic Studies. Cell. 2019;177:26-31. doi:10.1016/j.cell.2019.02. 04821. Kunkle BW, Grenier-Boley B, Sims R, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat Genet. 2019;51:414-430. doi:10.1038/s41588-019-0358-222. Ryman DC, Acosta-Baena N, Aisen PS, et al. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014;83:253-260. doi:10.1212/WNL. 000000000000059623. Karch CM, Goate AM. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77:43-51. doi:10. 1016/j.biopsych.2014.05.00624. Llibre-Guerra JJ, Li Y, Allegri RF, et al. Dominantly inherited Alzheimer’s disease in Latin America: genetic heterogeneity and clinical phenotypes. Alzheimers Dement J Alzheimers Assoc. 2021;17:653- 664. doi:10.1002/alz.1222725. Lopera F, Ardilla A, Martínez A, et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA. 1997;277:793-799.26. Athan ES, Williamson J, Ciappa A, et al. A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. JAMA. 2001;286:2257-2263. doi:10.1001/jama. 286.18.225727. Yescas P, Huertas-Vazquez A, Villarreal-Molina MT, et al. Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer’s disease in Mexican families. Neurogenetics. 2006;7:195-200. doi:10.1007/s10048-006-0043-328. Murrell J, Ghetti B, Cochran E, et al. The A431E mutation in PSEN1 causing familial Alzheimer’s disease originating in Jalisco State, Mexico: an additional fifteen families. Neurogenetics. 2006;7:277-279. doi:10.1007/s10048-006-0053-129. Dumois-Petersen S, Gallegos-ArreolaMP,Magaña-TorresMT, PereaDíaz FJ, Ringman JM, Figuera LE. Autosomal dominant early onset Alzheimer’s disease in the Mexican state of Jalisco: high frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients. Am J Med Genet C Semin Med Genet. 2020;184:1023-1029. doi:10. 1002/ajmg.c.3186530. Soosman SK, Joseph-Mathurin N, Braskie MN, et al. Widespread white matter and conduction defects in PSEN1-related spastic paraparesis. Neurobiol Aging. 2016;47:201-209. doi:10.1016/j. neurobiolaging.2016.07.03031. Lalli MA, Cox HC, Arcila ML, et al. Origin of the PSEN1 E280A mutation causing early-onset Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2014;10:S277-S283.e10. doi:10.1016/j.jalz.2013. 09.00532. Sepulveda-Falla D, Glatzel M, Lopera F. Phenotypic profile of earlyonset familial Alzheimer’s disease caused by presenilin-1 E280A mutation. J Alzheimers Dis JAD. 2012;32:1-12. doi:10.3233/JAD2012-12090733. Acosta-Baena N, Sepulveda-Falla D, Lopera-Gómez CM, et al. Predementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol. 2011;10:213-220. doi:10.1016/S1474-4422(10)70323-934. Cochran JN, Acosta-Uribe J, Esposito BT, et al. Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred. Alzheimers Dement J Alzheimers Assoc. 2023;19(9):3835-3847. doi:10. 1002/alz.1302135. Arboleda-Velasquez JF, Lopera F, O’Hare M, et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat Med. 2019;25:1680-1683. doi:10. 1038/s41591-019-0611-336. Lopera F, Marino C, Chandrahas AS, et al. Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man. Nat Med. 2023;29:1243-1252. doi:10.1038/s41591-023- 02318-337. Bateman RJ, Xiong C, Benzinger TLS, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795-804. doi:10.1056/NEJMoa120275338. Moulder KL, Snider BJ, Mills SL, et al. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther. 2013;5:48. doi:10.1186/alzrt21339. Takada LT, Aláez-Verson C, Burgute BD, et al. Discovery and validation of dominantly inherited Alzheimer’s disease mutations in populations from Latin America. Alzheimers Res Ther. 2022;14:108. doi:10.1186/s13195-022-01052-140. Bateman RJ, Benzinger TL, Berry S, et al. The DIAN-TU Next Generation Alzheimer’s prevention trial: adaptive design and disease progression model. Alzheimers Dement J Alzheimers Assoc. 2017;13:8-19. doi:10.1016/j.jalz.2016.07.00541. Acosta-Uribe J, Aguillón D, Cochran JN, et al. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects. Genome Med. 2022;14:27. doi:10.1186/s13073-022-01035- 942. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261:921-923. doi:10.1126/science. 834644343. Reitz C, Jun G, Naj A, et al. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013;309:1483- 1492. doi:10.1001/jama.2013.297344. Choi KY, Lee JJ, Gunasekaran TI, et al. APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer’s Disease Risk in a Multiracial Sample. J Clin Med. 2019;8:1236. doi:10.3390/jcm808123645. Hendrie HC, Murrell J, Baiyewu O, et al. APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba. Int Psychogeriatr. 2014;26:977-985. doi:10.1017/ S104161021400016746. Rajabli F, Feliciano BE, Celis K, et al. Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. PLOS Genet. 2018;14:e1007791. doi:10.1371/journal.pgen. 100779147. Granot-Hershkovitz E, Tarraf W, Kurniansyah N, et al. APOE alleles’ association with cognitive function differs across Hispanic/Latino groups and genetic ancestry in the study of Latinos-investigation of neurocognitive aging (HCHS/SOL). Alzheimers Dement J Alzheimers Assoc. 2021;17:466-474. doi:10.1002/alz.1220548. Llibre-Guerra JJ, Li Y, Allen IE, et al. Race, Genetic Admixture, and Cognitive Performance in the Cuban Population. J Gerontol Ser A. 2022;77:331-338. doi:10.1093/gerona/glab06349. Llibre-Guerra JJ, Li J, Qian Y, et al. Apolipoprotein E (APOE) genotype, dementia, and memory performance among Caribbean Hispanic versus US populations. Alzheimers Dement. 2023;19:602-610. doi:10. 1002/alz.1269950. Marca-Ysabel MV, Rajabli F, Cornejo-Olivas M, et al. Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population. Neurobiol Aging. 2021;101:298.e11-298.e15. doi:10.1016/j.neurobiolaging.2020.10.00351. Naslavsky MS, Suemoto CK, Brito LA, et al. Global and local ancestry modulate APOE association with Alzheimer’s neuropathology and cognitive outcomes in an admixed sample. Mol Psychiatry. 2022;27:4800-4808. doi:10.1038/s41380-022-01729-x52. Blue EE, Horimoto ARVR, Mukherjee S, Wijsman EM, Thornton TA. Local ancestry at APOE modifies Alzheimer’s disease risk in Caribbean Hispanics. Alzheimers Dement. 2019;15:1524-1532. doi:10.1016/j.jalz.2019.07.01653. Griswold AJ, Celis K, Bussies PL, et al. Increased APOE ε4 expression is associated with the difference in Alzheimer’s disease risk from diverse ancestral backgrounds. Alzheimers Dement. 2021;17:1179- 1188. doi:10.1002/alz.1228754. McKhann GM, Knopman DS, Chertkow H, et al. 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 J Alzheimers Assoc. 2011;7:263-269. doi:10.1016/j.jalz.2011.03. 00555. Sperling RA, Aisen PS, Beckett LA, et al. Toward 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 J Alzheimers Assoc. 2011;7:280-292. doi:10.1016/j.jalz.2011.03.00356. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment 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 J Alzheimers Assoc. 2011;7:270-279. doi:10.1016/j.jalz.2011.03.00857. Parra MA, Orellana P, Leon T, et al. Biomarkers for dementia in Latin American countries: gaps and opportunities. Alzheimers Dement J Alzheimers Assoc. 2023;19:721-735. doi:10.1002/alz.1275758. Gustavo Cuña E, Schulz H, Tuzzi E, et al. Simulated and experimental phantom data for multi-center quality assurance of quantitative susceptibility maps at 3 T, 7 T and 9.4 T. Phys Medica PM Int J Devoted Appl Phys Med Biol Off J Ital Assoc Biomed Phys AIFB. 2023;110:102590. doi:10.1016/j.ejmp.2023.10259059. Moguilner S, Whelan R, Adams H, Valcour V, Tagliazucchi E, Ibáñez A. Visual deep learning of unprocessed neuroimaging characterises dementia subtypes and generalises across non-stereotypic samples. eBioMedicine. 2023;90:104540. doi:10.1016/j.ebiom.2023.10454060. Russo MJ, Gustafson D, Vázquez S, et al. Creation of the ArgentinaAlzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement J Alzheimers Assoc. 2014;10:S84-S87. doi:10.1016/j.jalz.2013.09.01561. Allegri RF, Pertierra L, Cohen G, et al. A biological classification for Alzheimer’s disease—Amyloid, Tau and Neurodegeneration (A/T/N): results from the Argentine-Alzheimer’s Disease Neuroimaging Initiative. Int Psychogeriatr. 2019;31:1837-1838. doi:10.1017/ S104161021900008562. Allegri RF, Chrem Méndez P, Calandri I, et al. Prognostic value of ATN Alzheimer biomarkers: 60-month follow-up results from the Argentine Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement Amst Neth. 2020;12:e12026. doi:10.1002/dad2.1202663. Patricio CM, Gabriela C, Julieta RM, et al. Concordance between 11C-PIB-PET and clinical diagnosis in a memory clinic. Am J Alzheimers Dis Other Demen. 2015;30:599-606. doi:10.1177/153331751557638764. Lopera F, Custodio N, Rico-Restrepo M, et al. A task force for diagnosis and treatment of people with Alzheimer’s disease in Latin America. Front Neurol. 2023;14:1198869. doi:10.3389/fneur.2023. 119886965. Carneiro CDG, Faria DDP, Coutinho AM, et al. Evaluation of 10- minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer’s disease. Braz J Psychiatry. 2022;44(5):495- 506. doi:10.47626/1516-4446-2021-237466. Hansson O, Edelmayer RM, Boxer AL, et al. The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc. 2022;18:2669-2686. doi:10.1002/alz.1275667. Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93:e1647-e1659. doi:10.1212/WNL. 000000000000808168. Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19:422-433. doi:10.1016/ S1474-4422(20)30071-569. Mattsson N, Cullen NC, Andreasson U, Zetterberg H, Blennow K. Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease. JAMA Neurol. 2019;76:791-799. doi:10.1001/jamaneurol.2019.076570. Verberk IMW, Thijssen E, Koelewijn J, et al. Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimers Res Ther. 2020;12:118. doi:10.1186/s13195-020-00682-771. Steinacker P, Anderl-Straub S, Diehl-Schmid J, et al. Serum neurofilament light chain in behavioral variant frontotemporal dementia. Neurology. 2018;91:e1390-e1401. doi:10.1212/WNL. 000000000000631872. Chouliaras L, Thomas A, Malpetti M, et al. Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2022;93:651-658. doi:10.1136/jnnp-2021-32778873. Duran-Aniotz C, Orellana P, Leon Rodriguez T, et al. Systematic Review: genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries. Front Neurol. 2021;12:663407. doi:10.3389/fneur.2021.66340774. García AM, DeLeon J, Tee BL. Neurodegenerative Disorders of Speech and Language: non-language-dominant Diseases. Encycl Behav Neurosci. 2022:66-80. 2nd Ed., Elsevier. doi:10.1016/B978-0- 12-819641-0.00042-675. Sanz C, Carrillo F, Slachevsky A, et al. Automated text-level semantic markers of Alzheimer’s disease. Alzheimers Dement Diagn Assess Dis Monit. 2022;14:e12276. doi:10.1002/dad2.1227676. Ferrante FJ, Migeot J, Birba A, et al. Multivariate word properties in fluency tasks reveal markers of Alzheimer’s dementia. Alzheimers Dement J Alzheimers Assoc. 2023;20(2):925-940. doi:10.1002/alz. 1347277. García AM, Arias-Vergara T, Vasquez-Correa JC, et al. Cognitive Determinants of Dysarthria in Parkinson’s Disease: an AutomatedMachine Learning Approach. Mov Disord. 2021;36:2862-2873. doi:10.1002/mds.2875178. García AM, Escobar-Grisales D, Vásquez Correa JC, et al. Detecting Parkinson’s disease and its cognitive phenotypes via automated semantic analyses of action stories. Npj Park Dis. 2022;8:163. doi:10. 1038/s41531-022-00422-879. Sanz C, Carrillo F, Slachevsky A, et al. Automated text-level semantic markers of Alzheimer’s disease. Alzheimers Dement Amst Neth. 2022;14:e12276. doi:10.1002/dad2.1227680. García AM, Johann F, Echegoyen R, et al. Toolkit to Examine Lifelike Language (TELL): an app to capture speech and language markers of neurodegeneration. Behav Res Methods. 2023. doi:10.3758/s13428- 023-02240-z81. García AM, De Leon J, Tee BL, Blasi DE, Gorno-Tempini ML. Speech and language markers of neurodegeneration: a call for global equity. Brain. 2023;146(12):4870-4879. doi:10.1093/brain/ awad253. awad253.82. Kretzschmar H. Brain banking: opportunities, challenges and meaning for the future. Nat Rev Neurosci. 2009;10:70-78. doi:10.1038/ nrn253583. Grinberg LT, Ferretti RE de L, Farfel JM, et al. Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains. Cell Tissue Bank. 2007;8:151-162. doi:10. 1007/s10561-006-9022-z84. Suemoto CK, Ferretti-Rebustini REL, Rodriguez RD, et al. Neuropathological diagnoses and clinical correlates in older adults in Brazil: a cross-sectional study. PLoS Med. 2017;14:e1002267. doi:10. 1371/journal.pmed.100226785. Grinberg LT, Nitrini R, Suemoto CK, et al. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clin Sao Paulo Braz. 2013;68:1140-1145. doi:10.6061/clinics/2013(08)1386. Schlesinger D, Grinberg LT, Alba JG, et al. African ancestry protects against Alzheimer’s disease-related neuropathology. Mol Psychiatry. 2013;18:79-85. doi:10.1038/mp.2011.13687. Taratuto AL, Piccardo P, Leiguarda R, et al. Creutzfeldt-Jakob disease. Report of 10 neuropathologically-verified cases in Argentina. Medicina (Mex). 1989;49:293-303.88. Riudavets MA, Sraka MA, Schultz M, et al. Gerstmann-SträusslerScheinker syndrome with variable phenotype in a new kindred with PRNP-P102L mutation. Brain Pathol Zurich Switz. 2014;24:142-147. doi:10.1111/bpa.1208389. Taratuto AL, Piccardo P, Reich EG, et al. Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease.Neurology. 2002;58:362-367. doi:10.1212/wnl.58.3.36290. Allegri RF, Bartoloni L, IturryM, et al.MM1+2C sporadic CreutzfeldtJakob disease presenting as rapidly progressive nonfluent aphasia. J Alzheimers Dis JAD. 2014;39:13-17. doi:10.3233/JAD-13035091. Riudavets MA, Bartoloni L, Troncoso JC, et al. Familial dementia with frontotemporal features associated with M146V presenilin-1 mutation. Brain Pathol Zurich Switz. 2013;23:595-600. doi:10.1111/bpa. 1205192. Littau JL, Velilla L, Hase Y, et al. Evidence of beta amyloid independent small vessel disease in familial Alzheimer’s disease. Brain Pathol Zurich Switz. 2022;32:e13097. doi:10.1111/bpa.1309793. Soto-Ospina A, Araque Marín P, Bedoya GJ, Villegas Lanau A. Structural Predictive Model of Presenilin-2 Protein and Analysis of Structural Effects of Familial Alzheimer’s DiseaseMutations.Biochem Res Int. 2021;2021:9542038. doi:10.1155/2021/954203894. Sepulveda-Falla D, Sanchez JS, Almeida MC, et al. Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia. Acta Neuropathol (Berl). 2022;144:589-601. doi:10.1007/s00401- 022-02467-895. Vélez JI, Lopera F, Silva CT, et al. Familial Alzheimer’s Disease and Recessive Modifiers. Mol Neurobiol. 2020;57:1035-1043. doi:10. 1007/s12035-019-01798-096. Reyes-Pablo AE, Campa-Córdoba BB, Luna-Viramontes NI, et al. National Dementia BioBank: a Strategy for the Diagnosis and Study of Neurodegenerative Diseases in México. J Alzheimers Dis. 2020;76:853-862. doi:10.3233/JAD-19101597. mdorsey. First-of-its-Kind DNA Biobank Opens in Peru. Aligning Sci Park 2021. accessed October 19, 2023. https://parkinsonsroadmap.org/ news/first-of-its-kind-dna-biobank-opens-in-peru98. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396:413-446. doi:10.1016/S0140-6736(20)30367-699. Mukadam N, Sommerlad A, Huntley J, Livingston G. Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. Lancet Glob Health. 2019;7:e596-603. doi:10.1016/S2214- 109X(19)30074-9100. Suemoto CK, Bertola L, Grinberg LT, et al. Education, but not occupation, is associated with cognitive impairment: the role of cognitive reserve in a sample from a low-to-middle-income country. Alzheimers Dement J Alzheimers Assoc. 2022;18:2079-2087. doi:10.1002/alz. 12542101. Santamaria-Garcia H, Sainz-Ballesteros A, Hernandez H, et al. Factors associated with healthy aging in Latin American populations.Nat Med. 2023;29:2248-2258. doi:10.1038/s41591-023-02495-1102. Risk factors related to population diversity and disparity determine healthy aging. Nat Med. 2023;29:2183-2184. doi:10.1038/s41591- 023-02531-0103. Nitrini R, Bottino CMC, Albala C, et al. Prevalence of dementia in Latin America: a collaborative study of population-based cohorts. Int Psychogeriatr. 2009;21:622-630. doi:10.1017/S1041610209009430104. Herrera-Perez E, Custodio N, Diaz M, et al. Epidemiology of neurocognitive disorders in adults from urban-marginalized areas: a door-to-door population-based study in Puente Piedra, Lima, Peru. Front Public Health. 2023;11:1228008. doi:10.3389/fpubh.2023. 1228008105. Resende E de PF, Tovar-Moll FF, Ferreira FM, et al. White Matter Microstructure in Illiterate and Low-Literate Elderly Brazilians: preliminary Findings. Cogn Behav Neurol Off J Soc Behav Cogn Neurol. 2018;31:193-200. doi:10.1097/WNN.0000000000000173106. De Resende EDPF, Xia F, Sidney S, et al. Higher literacy is associated with better white matter integrity and cognition in middle age. Alzheimers Dement Diagn Assess Dis Monit. 2022;14:e12363. doi:10. 1002/dad2.12363107. Resende E de PF, Rosen HJ, Chiang K, et al. Primary School Education May Be Sufficient toModerate aMemory-Hippocampal Relationship. Front Aging Neurosci. 2018;10:381. doi:10.3389/fnagi.2018.00381108. O’Shea DM, Langer K, Woods AJ, et al. Educational Attainment Moderates the Association Between Hippocampal Volumes and Memory Performances in Healthy Older Adults. Front Aging Neurosci. 2018;10:361. doi:10.3389/fnagi.2018.00361109. Kalaria RN, Maestre GE, Arizaga R, et al. Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 2008;7:812-826. doi:10.1016/S1474- 4422(08)70169-8110. Suemoto CK, Szlejf C, Santos IS, et al. Ideal vascular health and cognitive performance in the Brazilian Longitudinal Study of Adult Health. Eur J Neurol. 2021;28:71-80. doi:10.1111/ene.14532111. Suemoto CK, Mukadam N, Brucki SMD, et al. Risk factors for dementia in Brazil: differences by region and race. Alzheimers Dement. 2023;19:1849-1857. doi:10.1002/alz.12820112. Vergara RC, Zitko P, Slachevsky A, San Martin C, Delgado C. Population attributable fraction of modifiable risk factors for dementia in Chile. Alzheimers Dement Amst Neth. 2022;14:e12273. doi:10.1002/ dad2.12273113. Henríquez F, Cabello V, Baez S, et al. Multidimensional Clinical Assessment in Frontotemporal Dementia and Its Spectrum in Latin America and the Caribbean: a Narrative Review and a Glance at Future Challenges. Front Neurol. 2022;12:768591. doi:10.3389/ fneur.2021.768591114. REDONE.br – Neuroimmunology Brazilian Study Group Focused on COVID-19 and MS. Incidence and clinical outcome of Coronavirus disease 2019 in a cohort of 11,560 Brazilian patients with multiple sclerosis. Mult Scler Houndmills Basingstoke Engl. 2021;27:1615-1619. doi:10.1177/1352458520978354115. Crivelli L, Calandri IL, Suemoto CK, et al. Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAmFINGERS): study design and harmonization. Alzheimers Dement J Alzheimers Assoc. 2023;19(9):4046-4060. doi:10.1002/alz.13101116. Maito MA, Santamaría-García H, Moguilner S, et al. Classification of Alzheimer’s disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: a cross sectional observational study. Lancet Reg Health— Am. 2023;17:100387. doi:10.1016/j.lana.2022.100387117. Sanz Perl Y, Fittipaldi S, Gonzalez Campo C, et al. Model-based whole-brain perturbational landscape of neurodegenerative diseases. eLife. 2023;12:e83970. doi:10.7554/eLife.83970118. Santamaria-Garcia H, Moguilner S, Rodriguez-Villagra OA, et al. The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations. GeroScience. 2023;45(4):2405-2423. doi:10.1007/s11357- 023-00755-z119. Ibáñez A, Legaz A, Ruiz-Adame M. Addressing the gaps between socioeconomic disparities and biological models of dementia. Brain. 2023;146:3561-3564. doi:10.1093/brain/awad236120. Ibanez A, Parra MA, Butler C. Latin America and the Caribbean Consortium on Dementia (LAC-CD). The Latin America and the Caribbean Consortium on Dementia (LAC-CD): from Networking to Research to Implementation Science. J Alzheimers Dis JAD. 2021;82:S379-S394. doi:10.3233/JAD-201384121. Ibanez A, Yokoyama JS, Possin KL, et al. The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): driving Multicentric Research and Implementation Science. Front Neurol. 2021;12:631722. doi:10.3389/fneur.2021.631722122. Slachevsky A, Zitko P, Martínez-Pernía D, et al. GERO Cohort Protocol, Chile, 2017-2022: community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly. BMC Geriatr. 2020;20:505. doi:10.1186/s12877-020-01866-4123. Santamaría-García H, Ogonowsky N, Baez S, et al. Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study. BMC Neurol. 2022;22:454. doi:10.1186/s12883-022-02954-1124. Migeot J, Calivar M, Granchetti H, Ibáñez A, Fittipaldi S. Socioeconomic status impacts cognitive and socioemotional processes in healthy ageing. Sci Rep. 2022;12:6048. doi:10.1038/s41598-022- 09580-4125. De Felice FG, Gonçalves RA, Ferreira ST. Impaired insulin signalling and allostatic load in Alzheimer disease. Nat Rev Neurosci. 2022;23:215-230. doi:10.1038/s41583-022-00558-9126. Migeot JA, Duran-Aniotz CA, Signorelli CM, Piguet O, Ibáñez A. A predictive coding framework of allostatic-interoceptive overload in frontotemporal dementia. Trends Neurosci. 2022;45:838-853. doi:10. 1016/j.tins.2022.08.005127. Crivelli L. LatAm-FINGERS (Latin America): world-Wide FINGERS network: the first global network of multidomain dementia prevention trials. Alzheimers Dement. 2020;16. doi:10.1002/alz.046953128. Kivipelto M, Solomon A, Ahtiluoto S, et al. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 2013;9:657- 665. doi:10.1016/j.jalz.2012.09.012129. Allegri RF, Bagnati P, Brucki S, Nitrini R. South America’s AD Clinical Trials Experience. Glob Clin Trials Alzheimers Dis. 2014:219-230. doi:10.1016/B978-0-12-411464-7.00013-4. Elsevier.130. Llibre-Guerra JJ, Heavener A, Brucki SMD, et al. A call for clinical trial globalization in Alzheimer’s disease and related dementia. Alzheimers Dement J Alzheimers Assoc. 2023;19:3210-3221. doi:10. 1002/alz.12995131. Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement Transl Res Clin Interv. 2023;9:e12385. doi:10.1002/trc2.12385132. de Miranda LFJR, Matoso R de O, Rodrigues MV, et al. Factors influencing possible delay in the diagnosis of Alzheimer’s disease: findings from a tertiary Public University Hospital. Dement Neuropsychol. 2011;5:328-331. doi:10.1590/S1980-57642011DN05040011133. Chávez-Fumagalli MA, Shrivastava P, Aguilar-Pineda JA, et al. Diagnosis of Alzheimer’s Disease in Developed and Developing Countries: systematic Review and Meta-Analysis of Diagnostic Test Accuracy. J Alzheimers Dis Rep. 2021;5:15-30. doi:10.3233/ADR-200263134. Mills SM, Mallmann J, Santacruz AM, et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013;169:737-743. doi:10.1016/j.neurol.2013.07.017135. Joseph-Mathurin N, Llibre-Guerra JJ, Li Y, et al. Amyloid-Related Imaging Abnormalities in the DIAN-TU-001 Trial of Gantenerumab and Solanezumab: lessons from a Trial in Dominantly Inherited Alzheimer Disease. Ann Neurol. 2022;92:729-744. doi:10.1002/ana. 26511136. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med. 2023;388:9-21. doi:10.1056/ NEJMoa2212948137. Roberts M, Sevastou I, Imaizumi Y, et al. Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer’s disease. Acta Neuropathol Commun. 2020;8:13. doi:10.1186/s40478- 020-0884-2138. Rios-Romenets S, Lopera F, Sink KM, et al. Baseline demographic, clinical, and cognitive characteristics of the Alzheimer’s Prevention Initiative (API) Autosomal-Dominant Alzheimer’s Disease Colombia Trial. Alzheimers Dement J Alzheimers Assoc. 2020;16:1023-1030. doi:10.1002/alz.12109139. Ltd FH-LR. Roche provides update on Alzheimer’s Prevention Initiative study evaluating crenezumab in autosomal dominant Alzheimer’s disease. GlobeNewswire News Room 2022. (accessed August 31, 2023). https://www.globenewswire.com/newsrelease/2022/06/16/2463591/0/en/Roche-provides-update-onAlzheimer-s-Prevention-Initiative-study-evaluating-crenezumabin-autosomal-dominant-Alzheimer-s-disease.html140. SA AI. Detailed Data From the Phase II Crenezumab Alzheimer’s Prevention Initiative Study in Autosomal Dominant Alzheimer’s Disease Presented at AAIC. GlobeNewswire News Room 2022. Accessed August 31, 2023. https://www.globenewswire.com/newsrelease/2022/08/02/2490659/0/en/Detailed-Data-From-thePhase-II-Crenezumab-Alzheimer-s-Prevention-Initiative-Studyin-Autosomal-Dominant-Alzheimer-s-Disease-Presented-atAAIC.html.50265009720Alzheimer’s diseaseBiomarkersDementiaGeneticsHispanicsLatin AmericaORIGINALAdvancements in dementia research, diagnostics, and care inLatin America.pdfAdvancements in dementia research, diagnostics, and care inLatin America.pdfArtículoapplication/pdf400837https://repositorio.cuc.edu.co/bitstreams/0f522f12-b80a-439e-86f1-2cd5bbad0b4c/downloadd0ae1872fc44cdfd10d22af66d7f105bMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.cuc.edu.co/bitstreams/cbd3d760-cd7c-4c24-88b2-e5fa392e4258/download2f9959eaf5b71fae44bbf9ec84150c7aMD52TEXTAdvancements in dementia research, diagnostics, and care inLatin America.pdf.txtAdvancements in dementia research, diagnostics, and care inLatin America.pdf.txtExtracted texttext/plain100412https://repositorio.cuc.edu.co/bitstreams/a742d2d0-0918-4200-8f4b-993e041716e8/download1a470db71b16585340cf795737c40fe3MD53THUMBNAILAdvancements in dementia research, diagnostics, and care inLatin America.pdf.jpgAdvancements in dementia research, diagnostics, and care inLatin America.pdf.jpgGenerated Thumbnailimage/jpeg17148https://repositorio.cuc.edu.co/bitstreams/ac2ae389-e310-4372-800f-130705514742/downloadb9bd98a766359b11eb1d91d195f102a0MD5411323/13363oai:repositorio.cuc.edu.co:11323/133632024-09-24 03:01:55.206https://creativecommons.org/licenses/by/4.0/© 2024 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.open.accesshttps://repositorio.cuc.edu.coRepositorio de la Universidad de la Costa CUCrepdigital@cuc.edu.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 |