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 developmentPublication Multi-feature computational framework for combined signatures of dementia in underrepresented settings(2022) Moguilner, Sebastián; Birba, Agustina; Fittipaldi, Sol; Gonzalez, Cecilia; Tagliazucchi, Enzo; Reyes, Pablo; Matallana, Diana; Parra, Mario; Slachevsky Chonchol, Andrea; Farías, Gonzalo; Cruzat, Josefina; García, Adolfo; Eyre, Harris; La Joie, Renaud; Rabinovici, Gil; Whelan, Robert; Ibáñez, AgustínObjective.The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings.Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat).Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens).Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data.Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countriesPublication Cardiovascular risk factors and the allostatic interoceptive network in dementia(2025) Hazelton, Jessica; Migeot, Joaquín; Gonzalez, Raul; Altschuler, Florencia; Duran, Claudia; Wen, Olivia; Galván, Dante; Barttfeld, Pablo; Medel , Vicente; González, Cecilia; Castro, Ana; Hernández, Hernán; Gonzalez, Carolina; Castaner, Olga; Hu, Kun; Li, Peng; Maria Isabel Behrens; Behrens, Maria Isabel; Bruno, Martin; Cardona, Juan; Custodio, Nilton; Santamaria, Hernando; Garcia, Adolfo; Godoy, Maria; Avila, José; Maito, Marce; Matallana, Diana; Miller, Bruce; Lopera, Francisco; Okada , Maira; Pina, Stefanie; Possin, Katherine; France, Elisa de Paula; Reyes, Pablo; Slachevsky Chonchol, Andrea; Sosa, Ana; Takada, Leonel; Yokoyama, Jennifer; Ibanez, AgustinAims: Cardiovascular risk factors, such diabetes, hypertension, blood pressure, obesity, and smoking, are linked with allostatic-interoception-the continuous monitoring of internal bodily states in anticipation of environmental demands. These risk factors are associated with dementia risk. How these factors affect brain networks vulnerable to neurodegeneration and involved in allostatic-interoception, such as the Allostatic-Interoceptive Network (AIN), is unknown. We investigated the relationship between cardiovascular risk and AIN structure and function in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Methods and results: We recruited 1501 participants (304 with FTLD, 512 with AD, and 685 healthy controls) from the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat). A cardiovascular risk score was calculated based on: age, sex, diabetes, hypertension, systolic blood pressure, body mass index, and smoking status. Cardiovascular risk was associated with grey matter integrity and functional connectivity in age- and sex-matched patient-control groups focusing on predefined regions of interest within the AIN. Higher cardiovascular risk was associated with reduced structural integrity and functional connectivity within the AIN in both FTLD and AD. FTLD patients showed more extensive structural and functional connectivity disruptions throughout the AIN. In AD patients, structural reductions in the AIN were prominent, with functional connectivity restricted to the hippocampus, parahippocampal gyrus, and orbitofrontal regions. Conclusion: Cardiovascular risk factors appear to adversely impact the AIN structure and function, with disease-specific patterns of vulnerability. Results underscore the importance of integrating cardiovascular health into models of neurodegenerative disease and managing cardiovascular health to support brain integrity in dementia.Publication Social exposome and brain health outcomes of dementia across Latin America(2025) Migeot, Joaquin; Pina, Stefanie; Hernandez, Hernan; Gonzalez, Raul; Legaz, Agustina; Fittipaldi, Sol; Resende, Elisa de Paula França; Duran, Claudia; Avila, Jose; Behrens, Maria Isabel; Bruno, Martin; Cardona, Juan; Custodio, Nilton; García, Adolfo; Godoy, Maria; Hu, Kun; Lanata, Serggio; Lawlor, Brian; Lopera, Francisco; Maito, Marcelo; Matallana, Diana; Miller, Bruce; Miranda, J Jaime; Okada, Maira; Reyes, Pablo; Santamaria, Hernando; Slachevsky Chonchol, Andrea; Sosa, Ana; Takada, Leonel; Torres, Jacqueline; Vanneste, Sven; Valcour, Victor; Wen, Olivia; Yokoyama, Jennifer; Possin, Katherine; Ibañez, AgustinA multidimensional social exposome (MSE)-the combined lifespan measures of education, food insecurity, financial status, access to healthcare, childhood experiences, and more-may shape dementia risk and brain health over the lifespan, particularly in underserved regions like Latin America. However, the MSE effects on brain health and dementia are unknown. We evaluated 2211 individuals (controls, Alzheimer's disease, and frontotemporal lobar degeneration) from a non-representative sample across six Latin American countries. Adverse exposomes associate with poorer cognition in healthy aging. In dementia, more complex exposomes correlate with lower cognitive and functional performance, higher neuropsychiatric symptoms, and brain structural and connectivity alterations in frontal-temporal-limbic and cerebellar regions. Food insecurity, financial resources, subjective socioeconomic status, and access to healthcare emerge as critical predictors. Cumulative exposome measures surpass isolated factors in predicting clinical-cognitive profiles. Multiple sensitivity analyses confirm our results. Findings highlight the need for personalized approaches integrating MSE across the lifespan, emphasizing prevention and interventions targeting social disparities.