Browsing by Author "Kosik, Kenneth"
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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 developmentPublication Driving research on successful aging and neuroprotection in Latin America: Insights from the inaugural symposium on brain resilience and healthy longevity(2025) Quiroz, Yakeel; Aguillón, David; Arboleda, Joseph; Bocanegra, Yamile; Cardona, Gloria; Corrada, Maria; Diez, Ibai; Garcia, Elkin; Kosik, Kenneth; Martinez, Lusiana; Pineda, David; Posada, Rafael; Roman, Norbel; Sepulveda, Diego; Slachevsky Chonchol, Andrea; Soto, Marcio; Tabilo, Evelyn; Vasquez, Daniel; Villegas, AndrésIntroduction: Global life expectancy has steadily increased in recent decades, resulting in a significant rise in the number of individuals aged 80 years and older. This trend is also evident in Latin America, where life expectancy is improving, though at varying rates across countries and regions. Methods: Partnering with the Neurosciences Group of Antioquia (GNA), we launched a Colombian study on resilience in families with autosomal dominant Alzheimer's disease and the oldest-old population. Over the past 2 years, the project has expanded to include participants from Peru, Chile, and Costa Rica. Results: This research led to the first symposium on Brain Resilience and Healthy Longevity, held in Medellín, Colombia, in August 2024. Discussion: The article summarizes key discussions from the symposium, highlighting the most promising opportunities for brain resilience and prevention research in the region and offering recommendations for future research to promote healthy aging and dementia-free communities. Highlights: Uncovering the genetic and physiological drivers of cognitive resilience, neurodegeneration resistance, and healthy longevity is essential for maintaining brain function as we age. "Superagers" and cognitively resilient individuals from Latin American families with Alzheimer's disease offer valuable insights into brain protection mechanisms. Studying the interplay of socio-environmental and genetic factors in the oldest-old is key to understanding healthy longevity and improving dementia prevention. The inaugural Brain Resilience and Healthy Longevity Symposium highlights the need for global collaboration to uncover factors that drive cognitive resilience and healthy aging in Latin America, advancing dementia prevention.Publication The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations(2023) Santamaria, Hernando; Moguilner, Sebastian; Rodriguez, Odir; Botero, Felipe; Pina, Stefanie; O’Donovan, Gary; Albala, Cecilia; Matallana, Diana; Schulte, Michael; Slachevsky Chonchol, Andrea; Yokoyama, Jennifer; Possin, Katherine; Ndhlovu, Lishomwa; Al‑Rousan, Tala; Corley, Michael; Kosik, Kenneth; Muniz, Graciela; Miranda, J. Jaime; Ibanez, AgustinGlobal initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.