Browsing by Author "Bruno, Martin"
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Publication 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 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 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.