Person: Slachevsky Chonchol, Andrea
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Slachevsky Chonchol
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Andrea
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Andrea María Slachevsky Conchol
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Publication Educational disparities in brain health and dementia across Latin America and the United States(2024) Gonzalez, Raul; Legaz, Agustina; Moguilner, Sebastián; Cruzat, Josephine; Hernández, Hernán; Baez, Sandra; Cocchi, Rafael; Coronel, Carlos; Medel,Vicente; Tagliazuchi, Enzo; Migeot, Joaquín; Ochoa, Carolina; Maito, Marcelo; Reyes, Pablo; Santamaria, Hernando; Godoy, Maria; Javande, Shireen; García, Adolfo; Matallana, Diana; Avila, José; Slachevsky Chonchol, Andrea; Behrens, María; Custodio, Nilton; Cardona, Juan; Brusco, Ignacio; Bruno, Martín; Sosa, Ana; Pina, Stefanie; Takada, Leonel; França, Elisa; Valcour, Victor; Possin, Katherine; De Oliveira, Maira; Lopera, Francisco; Lawlor, Brian; Hu, Kun; Miller, Bruce; Yokoyama, Jennifer; Gonzalez, Cecilia; Ibañez, AgustinBackground: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. Methods: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. Results: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. Discussion: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. Highlights: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.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 development