Person: Behrens, Maria Isabel
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Behrens
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Maria Isabel
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Publication 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 IsabelBrain 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.Publication 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 IsabelLos 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.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 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.Publication Qualitative and quantitative educational disparities and brain signatures in healthy aging and dementia across global settings(2025) Gonzalez, Raul; Cruzat, Josephine; Hernández, Hernán; Migeot, Joaquín; Legaz, Agustina; Santamaria, Hernando; Fittipaldi, Sol; Maito, Marcelo; Medel, Vicente; Tagliazucchi, Enzo; Barttfeld, Pablo; Franco-O'Byrne, Daniel; Castro, Ana; Borquez, Patricio; Avila, José; Behrens, Maria Isabel; Custodio, Nilton; Farombi, Temitope; García, Adolfo; Garcia, Indira; Godoy, Maria; Gonzalez, Cecilia; Hu, Kun; Lawlor, Brian; Matallana, Diana; Miller, Bruce; Okada, Maira; Pina, Stefanie; França, Elisa de Paula; Reyes, Pablo; Slachevsky Chonchol, Andrea; Takada, Leonel; Yener, Görsev; Coronel, Carlos; Ibañez, AgustinBackground: While education is crucial for brain health, evidence mainly relies on individual measures of years of education (YoE), neglecting education quality (EQ). The effect of YoE and EQ on aging and dementia has not been compared. Methods: We conducted a cross-sectional assessment of the effect of EQ and YoE on brain health in 7533 subjects from 20 countries, including healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). EQ was based on country-level quality indicators provided by the programme for international student assessment (PISA). After applying neuroimage harmonization, we examined its effect, along with YoE, on gray matter volume and functional connectivity. Regression models were adjusted for age, sex, and cognition, controlling for multiple comparisons. The influence of image quality was assessed through sensitivity analysis. Data collection was conducted between June 1 and October 30, 2024. Findings: Less EQ and YoE were associated with brain alterations across groups. However, EQ had a stronger influence, mainly targeting the critical areas of each condition. At the whole-brain level, EQ influenced volume (HCs: Δmean = 2·0 [1·9-2·0] × 10-2, p < 10-5; AD: Δmean = 0·1 [-0·0 to 0·3] × 10-2, p = 0·18; FTLD: Δmean = 3·5 [3·0-4·0] × 10-2, p < 10-5; all with 95% confidence intervals) and networks (HCs: Δmean = 13·5 [13·2-13·7] × 10-2, p < 10-5; AD: Δmean = 5·9 [5·2-6·7] × 10-2, p < 10-5; FTLD: Δmean = 13·2 [11·2-13·7] × 10-2, p < 10-5) 1·3 to 7·0 times more than YoE. These effects remain robust despite variations in income and socioeconomic factors at country and individual levels. Interpretation: The results support the need to incorporate education quality into studying and improving brain health, underscoring the importance of country-level measures. Funding: Multi-partner consortium to expand dementia research in Latin America (ReDLat).Publication Critical Review of the Methodological Shortcoming of Ambulatory Blood Pressure Monitoring and Cognitive Function Studies(2025) Haghayegh, Shahab; Hermida, Ramon; Smolensky, Michael; Jimenez, Mili; Duran, Claudia; Slachevsky Chonchol, Andrea; Behrens, Maria Isabel; Aguillon, David; Santamaria, Hernando; García, Adolfo; Matallana, Diana; Ibáñez, Agustín; Hu, KunGrowing evidence suggests that abnormal diurnal blood pressure rhythms may be associated with many adverse health outcomes, including increased risk of cognitive impairment and dementia. This study evaluates methodological aspects of research on bidirectional associations between ambulatory blood pressure monitoring (ABPM) patterns and cognitive function. By examining the 28 recent studies included in a recent systematic review on the association between ABPM patterns with cognitive function and risk of dementia, our review revealed several significant limitations in study design, sample characteristics, ABPM protocol, cognitive assessment, and data analysis. The major concerns include a lack of diversity in study populations with underrepresentation of Blacks and Latinos, a predominant focus on Alzheimer's disease or all-cause dementia without distinguishing other dementia subtypes, different and not standardized measures of cognition or dementia, prevalent use of 24 h monitoring without considering the adaption effect, inconsistent definitions of dipping status, and ignorance of individual differences in timings of daily activities such as bed and awakening times. In addition, confounding variables such as class, dose, and timing of antihypertensive medication are inadequately controlled or considered. Further, longitudinal studies were scarce examining the bidirectional relationship between ABPM patterns and cognitive decline over time. Collectively, these deficiencies undermine the reliability and generalizability of current findings. Addressing these methodological challenges is crucial for a more comprehensive understanding of diurnal blood pressure rhythms in diverse populations and for developing an evidence-based guideline for ambulatory monitoring and control of blood pressure across the sleep-wake cycle to prevent cognitive decline and dementia.