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Browsing by Author "Lopera, Francisco"

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Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City
(2024) Sosa, Ana; Brucki; Sonia; Crivelli, Lucia; Lopera, Francisco; Acosta, Daisy; Acosta, Juliana; Aguilar, Diego; Aguilar.Sara; Allegri, Ricardo; Bertolucci, Paulo; Calandri, Ismael; Carrillo, Maria; Chrem , Patricio; Cornejo, Mario; Custodio, Nilton; Damian, Andrés; Cruz , Leonardo; Duran, Claudia; García, Adolfo; García, Carmen; Gonzales, Mitzi; Grinberg, Lea; Ibanez, Agustin; Illanes, Maryenela; Jack, Clifford; Leon, Jorge; Llibre, Jorge; Luna, José; Matallana, Diana; Miller, Bruce; Naci, Lorina; Parra, Mario; Pericak, Margaret; Piña, Stefanie; França, Elisa de Paula; Ringman, John; Sevlever, Gustavo; Slachevsky Chonchol, Andrea; Kimie, Claudia; Valcour, Victor; Villegas, Andres
Introduction: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. Methods: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. Results: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. Discussion: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.
Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations
(2024) Moguilner, Sebastian; Baez, Sandra; Hernandez, Hernan; Migeot, Joaquín; Legaz, Agustina; Gonzalez, Raul; Farina, Francesca; Prado, Pavel; Cuadros, Jhosmary; Tagliazucchi, Enzo; Altschuler, Florencia; Maito, Marcelo; Godoy, María; Cruzat, Josefina; Valdes, Pedro; Lopera, Francisco; Ochoa, John; Gonzalez, Alfredis; Bonilla, Jasmin; Gonzalez, Rodrigo; Anghinah, Renato; d'Almeida, Luís; Fittipaldi, Sol; Medel, Vicente; Olivares, Daniela; Yener, Görsev; Escudero, Javier; Babiloni, Claudio; Whelan, Robert; Güntekin, Bahar; Yırıkoğulları, Harun; Santamaria, Hernando; Fernández, Alberto; Huepe, David; Di Caterina, Gaetano; Soto, Marcio; Birba, Agustina; Sainz, Agustin; Coronel, Carlos; Yigezu, Amanuel; Behrens, Maria Isabel
Los relojes cerebrales capturan la diversidad y las disparidades en el envejecimiento y la demencia en poblaciones geográficamente diversas. Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations. Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.
Author Correction: the BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds
(2024) Prado, Pavel; Medel, Vicente; González, Raúl; Sainz, Agustín; Vidal, Víctor; Santamaría, Hernando; Moguilner, Sebastián; Mejía, Jhony; Slachevsky Chonchol, Andrea; Behrens, Maria Isabel; Aguillón, David; Lopera, Francisco; Parra, Mario; Matallana, Diana; Adrián, Marcelo; García, Adolfo; Custodio, Nilton; Ávila, Alberto; Piña, Stefanie; Birba, Agustina; Fittipaldi, Sol; Legaz, Agustina; Ibáñez, Agustín
In this article the author name Maria Isabel Behrens was incorrectly written as Maria Isabel Beherens. The original article has been corrected.
Biomarkers for dementia in Latin American countries: Gaps andopportunities
(2023) Parra, Mario A.; Orellana, Paulina; León, Tomas; Victoria, Cabello G.; Henriquez, Fernando; Gomez, Rodrigo; Avalos, Constanza; Damian, Andres; Slachevsky Chonchol, Andrea; Ibañez, Agustin; Zetterberg, Henrik; Tijms, Betty M.; Yokoyama, Jennifer S.; Piña-Escudero, Stefanie D.; Cochran, Nicholas; Matallana, Diana L.; Acosta, Daisy; Allegri, Ricardo; Arias-Suáres, Bianca P.; Barra, Bernardo; Behrens, María Isabel; Brucki, Sonia M.D.; Busatto, Geraldo; Caramelli, Paulo; Castro-Suarez, Sheila; Contreras, Valeria; Custodio, Nilton; Dansilio, Sergio; De la Cruz-Puebla, Myriam; Cruz de Souza, Leonado; Díaz, Monica M.; Duque, Lissette; Farias, Gonzalo A.; Ferreira, Sergio T.; Magrath Guimet, Nahuel; Kmaid, Ana; Lira, David; Lopera, Francisco; Mar Meza, Beatriz; Miotto, Eliane C.
Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC)countries remains a serious barrier. Here, we reported a survey to explore the ongo-ing work, needs, interests, potential barriers, and opportunities for future studiesrelated to biomarkers. The results show that neuroimaging is the most used biomarker(73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cere-brospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears toundermine the implementation of biomarkers in clinical or research settings, followedby insufficient infrastructure and training. The survey revealed that despite the abovebarriers, the region holds a great potential to advance dementia biomarkers research.Considering the unique contributions that LAC could make to this growing field,we highlight the urgent need to expand biomarker research. These insights allowedus to propose an action plan that addresses the recommendations for a biomarkerframework recently proposed by regional experts.
Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations
(2024) Moguilner, Sebastian; Baez, Sandra; Hernandez, Hernan; Migeot, Joaquín; Legaz, Agustina; Gonzalez, Raul; Farina, Francesca; Prado, Pavel; Cuadros, Jhosmary; Tagliazucchi, Enzo; Altschuler, Florencia; Maito, Marcelo; Godoy, María; Cruzat, Josefina; Valdes, Pedro; Lopera, Francisco; Ochoa, John; González, Alfredis; Bonilla, Jazmín; Gonzalez, Rodrigo; Anghinah, Renato; d'Almeida, Luis; Fittipaldi, Sol; Medel, Vicente; Olivares, Daniela; Yener, Görsev; Escudero, Javier; Babiloni, Claudio; Whelan, Robert; Guntekin, Bahar; Yırıkoğulları, Harun; Santamaria, Hernando; Fernández, Alberto; Huepe, David; Di Caterina, Gaetano; Soto, Marcio; Birba, Agustina; Sainz, Agustin; Coronel, Carlos; Yigezu, Amanuel; Behrens, Maria Isabel
Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging. Los relojes cerebrales, que cuantifican las discrepancias entre la edad cerebral y la edad cronológica, son prometedores para comprender la salud y la enfermedad cerebral. Sin embargo, se desconoce el impacto de la diversidad (incluida la geográfica, socioeconómica, sociodemográfica, sexual y neurodegenerativa) en la brecha de edad cerebral. Analizamos conjuntos de datos de 5306 participantes en 15 países (7 países de América Latina y el Caribe (ALC) y 8 países no pertenecientes a ALC). Con base en interacciones de orden superior, desarrollamos una arquitectura de aprendizaje profundo de brecha de edad cerebral para imágenes de resonancia magnética funcional (2953) y electroencefalografía (2353). Los conjuntos de datos comprendían controles sanos e individuos con deterioro cognitivo leve, enfermedad de Alzheimer y demencia frontotemporal variante conductual. Los modelos LAC evidenciaron edades cerebrales más avanzadas (imágenes por resonancia magnética funcional: error direccional medio = 5,60, error cuadrático medio (rmse) = 11,91; electroencefalografía: error direccional medio = 5,34, rmse = 9,82) asociadas con redes frontoposteriores en comparación con los modelos no LAC. La desigualdad socioeconómica estructural, la contaminación y las disparidades en la salud fueron predictores influyentes de mayores brechas de edad cerebral, especialmente en LAC (R² = 0,37, F² = 0,59, rmse = 6,9). Se encontró una brecha ascendente de edad cerebral desde controles sanos hasta deterioro cognitivo leve y enfermedad de Alzheimer. En LAC, observamos brechas de edad cerebral más grandes en mujeres en los grupos de control y enfermedad de Alzheimer en comparación con los respectivos hombres. Los resultados no se explicaron por variaciones en la calidad de la señal, la demografía o los métodos de adquisición. Estos hallazgos proporcionan un marco cuantitativo que captura la diversidad del envejecimiento cerebral acelerado.
Classification of Alzheimer’s disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: a cross sectional observational study
(2023) Maito, Marcelo Adrián; Santamaría-García, Hernando; Moguilner, Sebastián; Possin, Katherine L.; Godoy, María E.; Avila-Funes, José Alberto; Behrens, Maria Isabel; Brusco, Ignacio L. Maira Okada de Oliveira,b,r,s,ae Stefanie D. Pina-Escuder; Bruno, Martín A.; Cardona, Juan F.; Custodio, Nilton; García, Adolfo M.; Javandel, Shireen; Lopera, Francisco; Matallana, Diana L.; Miller, Bruce; Okada de Oliveira, Maira; Pina Escudero, Stefanie; Slachevsky Chonchol, Andrea; Ana L Sosa Ortiz; Takada, Leonel T.; Tagliazuchi, Enzo; Valcour, Victor; Yokoyama, Jennifer S.; Ibañez, Agustín
Background Global brain health initiatives call for improving methods for the diagnosis of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. Methods This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). Findings A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Interpretation Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region.
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
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, Agustin
Background: 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.
The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds
(2023) Prado, Pavel; Medel, Vicente; Gonzalez, Raul; Sainz, Agustín; Vidal , Victor; Santamaría, Hernando; Moguilner, Sebastian; Mejia, Jhony; Slachevsky Chonchol, Andrea; Behrens, Maria; Aguillon, David; Lopera, Francisco; Parra, Mario; Matallana,Diana; Maito, Marcelo; Garcia, Adolfo; Custodio, Nilton; Ávila, Alberto; Piña, Stefanie; Birba, Agustina; Fittipaldi, Sol; Legaz, Agustina; Ibañez, Agustín
The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson's disease (PD), and 250 healthy controls (HCs). This dataset (62.7 ± 9.5 years, age range 21-89 years) was collected through a multicentric effort across five Latin American countries to address the need for affordable, scalable, and available biomarkers in regions with larger inequities. The BrainLat is the first regional collection of clinical and cognitive assessments, anatomical magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), diffusion-weighted MRI (DWI), and high density resting-state electroencephalography (EEG) in dementia patients. In addition, it includes demographic information about harmonized recruitment and assessment protocols. The dataset is publicly available to encourage further research and development of tools and health applications for neurodegeneration based on multimodal neuroimaging, promoting the assessment of regional variability and inclusion of underrepresented participants in research.
The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science
(2021) Ibáñez, Agustín; Yokoyama, Jennifer S.; Possin, Katherine L.; Matallana, Diana; Lopera, Francisco; Nitrini, Ricardo; Takada, Leonel T.; Custodio, Nilton; Sosa Ortiz, Ana Luisa; Avila-Funes, José Alberto; Behrens, María Isabel; Slachevsky, Andrea; Myers, Richard M.; Cochran, J. Nicholas; Brusco, Luis Ignacio; Bruno, Martin A.; Brucki, Sonia M. D.; Pina-Escudero, Stefanie Danielle; Oliveira, Maira Okada de; Donnelly Kehoe, Patricio; Santamaria-Garcia, Hernando; Moguilner, Sebastián; Tagliazucchi, Enzo; Maito, Marcelo; Longoria Ibarrola, Erika Mariana; Pintado-Caipa, Maritza; Godoy, Maria Eugenia; Bakman, Vera; Javandel, Shireen; Kosik, Kenneth S.; Valcour, Victor; Miller, Bruce L.; The Latin America the Caribbean Consortium on Dementia (LAC-CD)
Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat’s regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer’s disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems’ infrastructure, and increase translational research collaborations across the continent.

Browsing by Author "Lopera, Francisco"

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