The exposome of brain aging across 34 countries
Year: 2026
Type: article
Study design: Observational Study
Abstract: The physical and social exposome affects human aging, and brain clocks may track its effects. However, most studies neglect multidomain exposures (physical, social and political) across diverse settings globally and their associations with brain aging. In this study, we characterized the associations between 73 country-level physical and social exposomal factors and multimodal brain age in 18,701 participants from 34 countries (healthy individuals and those with Alzheimer's disease, frontotemporal lobar degeneration or mild cognitive impairment). Exposome effects were assessed using generalized additive models and meta-analytic frameworks. Aggregated exposome models explained up to 15.5-fold more variance than individual exposures (delta Akaike information criterion (ΔAIC): 2,034-3,127). Physical exposome was primarily associated with accelerated structural brain aging (limbic, subcortical and cerebellar regions), whereas social exposome was more strongly associated with functional brain aging (frontotemporal and limbic networks). Exposome burden accounted for 3.3-9.1-fold higher risk of accelerated aging, exceeding effects of clinical diagnoses. Findings were out-of-sample validated in cross-sectional and longitudinal designs, remained consistent across clinical subgroups and persisted after adjustment for demographics, age correction bias, cognition, scanner type and data quality. The exposome accelerates brain aging in health and disease, underscoring the need to address physical, social and political inequities.
Source: Nature Medicine
Authors: Agustina Legaz, Sebastian Moguilner, Pablo Barttfeld, Jhosmary Cuadros Castro, Dante Sebastián Galván Rial, Joaquin Migeot, Francesca R. Farina, Raul Gonzalez-Gomez, Salomón Salazar-Londoño, Tiago de Souza Azzi, Sarael Alcauter, Lucia Amoruso, Renato Anghinah, May Bakr, María Isabel Behrens, Martin A. Bruno, Juan Felipe Cardona, Christopher Chen, Olivier Colliot, Nilton Custodio, Quentin d’Acremont, Stéphanie Debette, Patrycja Dzianok, Bahar Güntekin, Jordi Huguet, Cecilia Jarne, Marc Joliot, Elissaios Karageorgiou, Eman M. Khedr, Sheri-Michelle Koopowitz, Ewa Kublik, Jinkook Lee, Leon Aksman, Susanna Lopez, Paula Margaretic, Diana Matallana, Sophie Matis, Andreas Miltiadous, Gabriela Novotni, Patricio Orio, Mario A. Parra, Simone Reppermund, Elisa de Paula França Resende, Giovanni Abrahão Salum, Andrea Slachevsky, Ana Luisa Sosa Ortiz, Leonel Tadao Takada, An Qi Toh, Alexandros Tzallas, Wei Wen, Robert Whelan, Görsev Yener, Jonathan Adrián Zegarra Valdivia, Athanasia Alexoudi, Faheem Arshad, Haisam Atta, Jose Alberto Avila-Funes, Jasmin Bonilla Santos, Ricardo Bruña, Sandra Milena Castelblanco-Toro, Brenda Nadia Chino Vilca, Carlos Coronel-Oliveros, Fabrice Crivello, Josephine Cruzat, Damián Dellavale, Catherina Dhooge, Gaetano Di Caterina, Javier Escudero, Juan Manuel Esquivias Farias, Laz Ude Eze, Tavia E. Evans, Temitope Farombi, Alberto Fernández, Sol Fittipaldi, Florencia Portillo, Gonzalo Forno Martinic, Adolfo M. García, Indira Garcia-Cordero, Rahul Gaurav, Maria Eugenia Godoy, Cecilia Gonzalez Campo, Alfredis González Hernández, Lütfü Hanoğlu, Jessica L. Hazelton, Rubén Herzog, Burcin Ikiz, Alfred Kongnyu Njamnshi, Ramon Landin-Romero, María Eugenia López, Marcelo Adrián Maito, Vicente Medel, Juan Pablo Morales Sepúlveda, John Fredy Ochoa Gómez, Chukwuanugo Ogbuagu, Maira Okada de Oliveira, Mehmet Ozansoy, Javier Palma-Espinosa, Saima Hilal, Juan Helen Zhou, Stefanie Danielle Piña Escudero, Julie Kay Pitman, Pavel Prado, Diego Ramírez González, Pablo Reyes, Hernando Santamaría García, Johannes Schröder, Jacobo Diego Sitt, Radwa Kamel Soliman, Marcio Soto-Añari, Nithin Thanissery, Lucas Toshio Ito, Ami Tsuchida, Christophe Tzourio, Harun Yırıkoğulları, Jennifer S. Yokoyama, David Aguillon, Bruce Miller, Suvarna Alladi, Yang Jiang, Arcadi Navarro, Claudio Babiloni, David Huepe Artigas, Olivier Piguet, Pedro Antonio Valdes Sosa, Cyprian M. Mostert, Masoud Tahmasian, Peng Li, Kun Hu, Sarah Genon, Dan J. Stein, Fernando Maestú, Michela Pievani, Mohamed Salama, Henry Brodaty, Perminder S. Sachdev, Brian Lawlor, Harris A. Eyre, J. Jaime Miranda, Sandra Baez, Enzo Tagliazucchi, Claudia Duran-Aniotz, Hernan Hernandez, Agustin Ibanez
Institutions: University of California, San Francisco, Adolfo Ibáñez University, University of San Andrés, Global Brain Health Institute, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Instituto de Investigaciones Psicológicas, Universidad Nacional Experimental del Táchira, Universidad Técnica Federico Santa María, Trinity College Dublin, University of Chicago, Montreal Neurological Institute and Hospital, Pontificia Universidad Javeriana, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, Universidad Nacional Autónoma de México, Ikerbasque, Basque Center on Cognition, Brain and Language, Universidade de São Paulo, American University in Cairo, Universidad del Desarrollo, Clínica Alemana, Hospital Clínico de la Universidad de Chile, University of Chile, Universidad Católica de Cuyo, Universidad del Valle, National University of Singapore, Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Institut du Cerveau, Instituto Peruano de Neurociencias, Université de Bordeaux, Bordeaux Population Health, Centre Hospitalier Universitaire de Bordeaux, Institut des Maladies Neurodégénératives, Instytut Biologii Doświadczalnej im. Marcelego Nenckiego, International Institute of Molecular and Cell Biology, Polish Academy of Sciences, Istanbul Medipol University, Pasqual Maragall Foundation, Barcelonaβeta Brain Research Center, National University of Quilmes, Aarhus University, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Neurological Institute of Athens, Assiut University Hospitals, Assiut University, University of Cape Town, University of Southern California, Sapienza University of Rome, Hospital Universitario San Ignacio, The University of Sydney, University of Ioannina, Ss. Cyril and Methodius University in Skopje, University of Valparaíso, University of Strathclyde, UNSW Sydney, Centre for Healthy Brain Ageing, Universidade Federal de Minas Gerais, Faculdade de Ciências Médicas de Minas Gerais, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Child Mind Institute, Hospital del Salvador, Instituto Nacional de Neurología y Neurocirugía, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Dokuz Eylül University, Universidad Complutense de Madrid, Achucarro Basque Center for Neuroscience, National and Kapodistrian University of Athens, University General Hospital Attikon, Evangelismos Hospital, National Institute of Mental Health and Neurosciences, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Universidad Cooperativa de Colombia, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Universidad de Deusto, Bariloche Atomic Centre, University of Edinburgh, Universidad de Guadalajara, David Umahi Federal University of Health Sciences Uburu, Radboud University Medical Center, University College Hospital, Ibadan, Universidad de Santiago de Chile, Universidad Surcolombiana, Consejo Superior de Investigaciones Científicas, Institute for Cross-Disciplinary Physics and Complex Systems, Universitat de les Illes Balears, Columbia University, Université de Yaoundé I, Central Hospital of Yaoundé, Brain Research Africa Initiative, Pontificia Universidad Católica de Chile, Finis Terrae University, Universidad de Antioquia, Nnamdi Azikiwe University Teaching Hospital, National University Health System, San Sebastián University, Heidelberg University, Universidad Católica San Pablo, Universidade Federal de São Paulo, University of Kentucky, Institució Catalana de Recerca i Estudis Avançats, Universitat Pompeu Fabra, Barcelona Institute of Science and Technology, Institut de Biologia Evolutiva, Centre for Genomic Regulation, University of Electronic Science and Technology of China, Cuban Neuroscience Center, Aga Khan University Nairobi, Forschungszentrum Jülich, University of Cologne, Düsseldorf University Hospital, University Hospital Cologne, Heinrich Heine University Düsseldorf, Harvard University, Massachusetts General Hospital, South African Medical Research Council, Centro San Giovanni di Dio Fatebenefratelli, Prince of Wales Hospital, The University of Texas Medical Branch at Galveston, Rice University, Universidad Peruana Cayetano Heredia, Universidad de Los Andes, Universidad de Buenos Aires
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $12,690
OpenAlex ID: W7148783718