Browsing by Author "Montesinos, Rosa"
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Publication Comprehensive Analysis of Genetic Contributions to Alzheimer’s Disease and Frontotemporal Dementia in Admixed Latin American Populations(2024) Acosta, Juliana; Pina, Stefanie; Cochran, Nicholas; Taylor, Jared; Warly, Caroline; Matallana, Diana; Tadao, Leonel; Bruno, Martin; Levine, Alexandra; George, Dawwod; Lopera, Francisco; Slachevsky Chonchol, Andrea; Behrens, María; Ávila, José; Zapata, Lina; Brusco, Luis; Custodio, Nilton; Ramos, Teresita; Bruna, Bárbara; Ponce, Daniela; Gelvez, Nancy; Lopez, Greizy; Gomez, Luisa; Buitrago, Carlos; Reyes, Pablo; Durón, Dafne; Pantazis, Caroline; Maito, Marcelo; Javandel, Shireen; Godoy, Maria; Bistue, Maria; Vitale, Dan; Nalls, Mike; Singleton, Andrew; Miller, Bruce; Ibáñez, Agustín; Kosik, Kenneth; Yokoyama, Jennifer; Montesinos, Rosa; França, Elisa de Paula; Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat)Background: Most research initiatives have emerged from high-income countries (HIC), leaving a gap in understanding the disease’s genetic basis in diverse populations like those in Latin American countries (LAC). ReDLat tackles this gap, focusing on LAC’s unique genetics and socioeconomic factors to identify specific Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) risk factors in Mexico, Colombia, Peru, Chile, Argentina, and Brazil. Method: We employed a comprehensive genetic analysis approach, integrating Whole Genome Sequencing (WGS), Exome Sequencing, and SNP arrays to understand the cohort’s unique genetic architecture.We conducted ancestry analysis and searched for disease-causing variants with mendelian inheritance, genome-wide association studies (GWAS), rare variant enrichment, and evaluation of Polygenic Risk Scores (PRS). Results: We recruited and genotyped an initial cohort of 1046 participants with AD, 423 with FTD, and 855 healthy controls (HC) between 2020 and 2023. Analysis is ongoing, and we expect to sequence ∼600 additional samples in the coming months. Ancestry analysis revealed tri-continental admixture, except for Brazil, which showed an additional Asian component (Figure 1). Top candidate gene rare variant enrichment associations (SKAT p < 0.05) were TREM2 for FTD and ABCA7 and ABCA1 for AD. GWAS identified a robust association with the APOE locus on chromosome 19 in AD vs. HC.. We tested an AD PRS developed in European populations by Bellenguez et al (2020). on our cohort using 83 single-nucleotide polymorphisms.. The PRS modestly distinguishes between all patients and HC (p = 2.4 × 10ˆ-12), AD vs. HC (p = 2.2 × 10ˆ-12), and even FTD vs. HC (p = 4.3 × 10ˆ-5), albeit with modest separation between groups, as expected for its application in a genetically admixed population. Conclusion: Our findings represent a pivotal step in understanding the genetic landscape of AD and FTD in admixed populations. They underscore the importance of including diverse populations in genetic research, paving the way for future studies. These findings have the potential to inform more personalized approaches to the diagnosis and treatment of neurodegenerative diseases in diverse global populations, as well as identify novel targets for therapeutic developmentItem Systematic Review of the Diagnostic Validity of Brief Cognitive Screenings for Early Dementia Detection in Spanish-Speaking Adults in Latin America(2020) Custodio, Nilton; Duque, Lissette; Montesinos, Rosa; Alva-Díaz, Carlos; Mellado, Martin; Slachevsky, AndreaObjectives: The aim of this study was to evaluate the validity of brief cognitive screening (BCS) tools designed to diagnose mild cognitive impairment (MCI) or dementia in Spanish-speaking individuals over the age of 50 years from Latin America (LA). Methods: A systematic search of titles and abstracts in Medline, Biomed Central, Embase, Scopus, Scirus, PsycINFO, LILACS, and SciELO was conducted. Inclusion criteria were papers written in English or Spanish involving samples from Spanish-speaking Latin American individuals published until 2018. Standard procedures were applied for reviewing the literature. The data related to the study sample, methodology, and procedures applied, as well as the performance obtained with the corresponding BCS, were collected and systematized. Results: Thirteen of 211 articles met the inclusion criteria. The studies primarily involved memory clinic-based samples, with the exception of two studies from an adult day-care center, one from a primary care clinic, and one from a community-based sample. All the studies originated from five of the 20 countries of LA and all used standardized diagnostic criteria for the diagnosis of dementia and MCI; however, the diagnostic protocols applied differed. Most studies reported samples with an average of 10 years of education and only one reported a sample with an average of <5 years of education. No publication to date has included an illiterate population. Although the Montreal cognitive assessment (MoCA) is the most widely-used BCS tool in LA, it is significantly influenced by education level. Conclusions: Although evidence is still limited, the findings from studies on LA populations suggest that MoCA requires cultural adaptations and different cutoff points according to education level. Moreover, the diagnostic validity of the INECO frontal screening (IFS) test should be evaluated in populations with a low level of education. Given the heterogeneity that exists in the levels of education in LA, more studies involving illiterate and indigenous populations are required.Publication Validation of Picture Free and Cued Selective Reminding Test for Illiteracy in Lima, Perú(2022) Montesinos, Rosa; Parodi, José; Díaz, Mónica; Herrera, Eder; Valeriano, Elizabeth; Soto, Ambar; Delgado, Carolina; Slachevsky Chonchol, Andrea; Custodio, NiltonDementia in Latin America is a crucial public health problem. Identifying brief cognitive screening (BCS) tools for the primary care setting is crucial, particularly for illiterate individuals. We evaluated tool performance characteristics and validated the free and total recall sections of the Free and Cued Selective Reminding Test-Picture version (FCSRT-Picture) to discriminate between 63 patients with early Alzheimer's disease dementia (ADD), 60 amnestic mild cognitive impairment (aMCI) and 64 cognitively healthy Peruvian individuals with illiteracy from an urban area. Clinical, functional, and cognitive assessments were performed. FCSRT-Picture performance was assessed using receiver operating characteristic curve analyses. The mean ± standard deviation scores were 7.7 ± 1.0 in ADD, 11.8 ± 1.6 in aMCI, and 29.5 ± 1.8 in controls. The FCSRT-Picture had better performance characteristics for distinguishing controls from aMCI compared with several other BCS tools, but similar characteristics between controls and early ADD. The FCSRT-Picture is a reliable BCS tool for illiteracy in Perú.