Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations

Moguilner, Sebastian and Baez, Sandra and Hernandez, Hernan and Migeot, Joaquín and Legaz, Agustina and Gonzalez-Gomez, Raul and Farina, Francesca R. and Prado, Pavel and Cuadros, Jhosmary and Tagliazucchi, Enzo and Altschuler, Florencia and Maito, Marcelo Adrián and Godoy, María E. and Cruzat, Josephine and Valdes-Sosa, Pedro A. and Lopera, Francisco and Ochoa-Gómez, John Fredy and Hernandez, Alfredis Gonzalez and Bonilla-Santos, Jasmin and Gonzalez-Montealegre, Rodrigo A. and Anghinah, Renato and d’Almeida Manfrinati, Luís E. and Fittipaldi, Sol and Medel, Vicente and Olivares, Daniela and Yener, Görsev G. and Escudero, Javier and Babiloni, Claudio and Whelan, Robert and Güntekin, Bahar and Yırıkoğulları, Harun and Santamaria-Garcia, Hernando and Lucas, Alberto Fernández and Huepe, David and Di Caterina, Gaetano and Soto-Añari, Marcio and Birba, Agustina and Sainz-Ballesteros, Agustin and Coronel-Oliveros, Carlos and Yigezu, Amanuel and Herrera, Eduar and Abasolo, Daniel and Kilborn, Kerry and Rubido, Nicolás and Clark, Ruaridh A. and Herzog, Ruben and Yerlikaya, Deniz and Hu, Kun and Parra, Mario A. and Reyes, Pablo and García, Adolfo M. and Matallana, Diana L. and Avila-Funes, José Alberto and Slachevsky, Andrea and Behrens, María I. and Custodio, Nilton and Cardona, Juan F. and Barttfeld, Pablo and Brusco, Ignacio L. and Bruno, Martín A. and Sosa Ortiz, Ana L. and Pina-Escudero, Stefanie D. and Takada, Leonel T. and Resende, Elisa and Possin, Katherine L. and de Oliveira, Maira Okada and Lopez-Valdes, Alejandro and Lawlor, Brian and Robertson, Ian H. and Kosik, Kenneth S. and Duran-Aniotz, Claudia and Valcour, Victor and Yokoyama, Jennifer S. and Miller, Bruce and Ibanez, Agustin (2024) Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations. Nature Medicine. ISSN 1078-8956 (https://doi.org/10.1038/s41591-024-03209-x)

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Abstract

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.

ORCID iDs

Moguilner, Sebastian, Baez, Sandra, Hernandez, Hernan, Migeot, Joaquín, Legaz, Agustina, Gonzalez-Gomez, Raul, Farina, Francesca R., Prado, Pavel, Cuadros, Jhosmary, Tagliazucchi, Enzo, Altschuler, Florencia, Maito, Marcelo Adrián, Godoy, María E., Cruzat, Josephine, Valdes-Sosa, Pedro A., Lopera, Francisco, Ochoa-Gómez, John Fredy, Hernandez, Alfredis Gonzalez, Bonilla-Santos, Jasmin, Gonzalez-Montealegre, Rodrigo A., Anghinah, Renato, d’Almeida Manfrinati, Luís E., Fittipaldi, Sol, Medel, Vicente, Olivares, Daniela, Yener, Görsev G., Escudero, Javier, Babiloni, Claudio, Whelan, Robert, Güntekin, Bahar, Yırıkoğulları, Harun, Santamaria-Garcia, Hernando, Lucas, Alberto Fernández, Huepe, David, Di Caterina, Gaetano ORCID logoORCID: https://orcid.org/0000-0002-7256-0897, Soto-Añari, Marcio, Birba, Agustina, Sainz-Ballesteros, Agustin, Coronel-Oliveros, Carlos, Yigezu, Amanuel, Herrera, Eduar, Abasolo, Daniel, Kilborn, Kerry, Rubido, Nicolás, Clark, Ruaridh A. ORCID logoORCID: https://orcid.org/0000-0003-4601-2085, Herzog, Ruben, Yerlikaya, Deniz, Hu, Kun, Parra, Mario A. ORCID logoORCID: https://orcid.org/0000-0002-2412-648X, Reyes, Pablo, García, Adolfo M., Matallana, Diana L., Avila-Funes, José Alberto, Slachevsky, Andrea, Behrens, María I., Custodio, Nilton, Cardona, Juan F., Barttfeld, Pablo, Brusco, Ignacio L., Bruno, Martín A., Sosa Ortiz, Ana L., Pina-Escudero, Stefanie D., Takada, Leonel T., Resende, Elisa, Possin, Katherine L., de Oliveira, Maira Okada, Lopez-Valdes, Alejandro, Lawlor, Brian, Robertson, Ian H., Kosik, Kenneth S., Duran-Aniotz, Claudia, Valcour, Victor, Yokoyama, Jennifer S., Miller, Bruce and Ibanez, Agustin;
CORE (COnnecting REpositories)