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

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Sebastian Moguilner, Sandra Baez, Hernan Hernandez, Joaquín Migeot, Agustina Legaz, Raul Gonzalez-Gomez, Francesca R. Farina, Pavel Prado, Jhosmary Cuadros, Enzo Tagliazucchi, Florencia Altschuler, Marcelo Adrián Maito, María E. Godoy, Josephine Cruzat, Pedro A. Valdes-Sosa, Francisco Lopera, John Fredy Ochoa-Gómez, Alfredis Gonzalez Hernandez, Jasmin Bonilla-Santos, Rodrigo A. Gonzalez-Montealegre et al. (55 additional authors not shown)

Published: 01 Dec 2024, Last Modified: 27 Feb 2026Nature MedicineEveryoneRevisionsBibTeXCC BY-SA 4.0
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.