Diversity-sensitive brain clocks linked to biophysical mechanisms in aging and dementia

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Coronel-Oliveros, Carlos and Moguilner, Sebastián and Hernandez, Hernan and Cruzat, Josephine and Baez, Sandra and Medel, Vicente and Cuadros, Jhosmary and Santamaria-Garcia, Hernando and Valdes-Sosa, Pedro A. and Lopera, Francisco and Ochoa-Gómez, John Fredy and González- Hernández, Alfredis and Bonilla-Santos, Jasmin and Gonzalez-Montealegre, Rodrigo A. and Aktürk, Tuba and Yıldırım, Ebru and Anghinah, Renato and Legaz, Agustina and Fittipaldi, Sol and Yener, Görsev G. and Escudero, Javier and Babiloni, Claudio and Lopez, Susanna and Whelan, Robert and Fernández, Alberto and Huepe, David and Di Caterina, Gaetano and Soto-Añari, Marcio and Gonzalez-Gomez, Raul and Herrera, Eduar and Abasolo, Daniel and Kilborn, Kerry and Rubido, Nicolás and Clark, Ruaridh and Herzog, Rubén and Yerlikaya, Deniz and Güntekin, Bahar and Deco, Gustavo and Prado, Pavel and Parra, Mario A. and Orio, Patricio and Tagliazucchi, Enzo and Lawlor, Brian and Ibanez, Agustin (2025) Diversity-sensitive brain clocks linked to biophysical mechanisms in aging and dementia. Nature Mental Health. ISSN 2731-6076

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Abstract

Brain clocks track the deviations between predicted brain age and chronological age (brain age gaps, BAGs). These BAGs can be used to measure accelerated aging, monitoring deviations from the healthy brain trajectories associated with brain diseases and different cumulative burdens. However, the underlying biophysical mechanisms associated with BAGs in aging and dementia remain unclear. Here, we combine source space connectivity (EEG) with generative brain modeling in healthy controls (HCs) from the global south and north, alongside Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) patients (N=1,399). BAGs in aging were influenced by geography (south>north), income (low>high), sex (female>male), and education (low>high), with larger BAGs in patients, especially females with AD. Biophysical modeling revealed BAGs related to hyperexcitability and structural disintegration in aging, while hypoexcitability and severe disintegration were linked to dementia. Our work sheds light on the biophysical mechanisms of accelerated aging and dementia in diverse populations.

ORCID iDs

Coronel-Oliveros, Carlos, Moguilner, Sebastián, Hernandez, Hernan, Cruzat, Josephine, Baez, Sandra, Medel, Vicente, Cuadros, Jhosmary, Santamaria-Garcia, Hernando, Valdes-Sosa, Pedro A., Lopera, Francisco, Ochoa-Gómez, John Fredy, González- Hernández, Alfredis, Bonilla-Santos, Jasmin, Gonzalez-Montealegre, Rodrigo A., Aktürk, Tuba, Yıldırım, Ebru, Anghinah, Renato, Legaz, Agustina, Fittipaldi, Sol, Yener, Görsev G., Escudero, Javier, Babiloni, Claudio, Lopez, Susanna, Whelan, Robert, Fernández, Alberto, Huepe, David, Di Caterina, Gaetano ORCID logoORCID: https://orcid.org/0000-0002-7256-0897, Soto-Añari, Marcio, Gonzalez-Gomez, Raul, Herrera, Eduar, Abasolo, Daniel, Kilborn, Kerry, Rubido, Nicolás, Clark, Ruaridh ORCID logoORCID: https://orcid.org/0000-0003-4601-2085, Herzog, Rubén, Yerlikaya, Deniz, Güntekin, Bahar, Deco, Gustavo, Prado, Pavel, Parra, Mario A. ORCID logoORCID: https://orcid.org/0000-0002-2412-648X, Orio, Patricio, Tagliazucchi, Enzo, Lawlor, Brian and Ibanez, Agustin;
CORE (COnnecting REpositories)