Mónica Otero, Felipe I. Carriel-Rubilar, Hernan Hernandez, Jhosmary Cuadros, Jorge G. Condado, Agustin Sainz-Ballesteros, Hernando Santamaria-Garcia, Agustina Legaz, Agustina Birba, Sol Fittipaldi, Francisco Lopera, John Ochoa-Gómez, David Aguillon, Alfredis González-Hernández, Jasmin Bonilla-Santos, Rodrigo A. Gonzalez-Montealegre, Görsev G. Yener, Bahar Güntekin, İlayda Kıyı, Tuba Aktürk, Ebru Yıldırım, Lütfü Hanoğlu, Renato Anghinah, Pedro A. Valdes-Sosa, Ronaldo Garcia-Reyes, Javier Escudero, Susanna Lopez, Robert Whelan, Alberto Fernández, Adolfo M. García, David Huepe, Marcio Soto-Añari, Eduar Herrera, Daniel Abasolo, Nicolás Rubido, Ruaridh A. Clark, Wael El-Deredy, Jesús M. Cortes, Mario A. Parra, Claudio Babiloni, Agustin Ibanez, Pavel Prado. Source-space EEG alpha activity reveals brain age gaps due to neurodegeneration and disparity. Communications Biology 9:740, 2026. [pdf]
Brain clocks are promising tools for evaluating brain health. However, most current methods rely on
structural neuroimaging. Functionally based approaches remain scarce, especially for assessing agerelated neurodegenerative diseases. This study examines whether the brain age gap (BAG), the
difference between chronological and predicted brain age, reflects neurodegeneration when
estimated from electroencephalographic resting-state (rsEEG) α-oscillations, a well-established
marker of brain functional aging. It also explores whether α-based brain clocks reflect
sociodemographic diversity and structural inequality. The BAG was computed using spectral
descriptors of α-activity in the rsEEG source space of 1228 healthy participants, individuals with mild
cognitive impairment (MCI), and patients with Alzheimer’s disease or behavioral variant
frontotemporal dementia, residing in 10 countries with varying levels of structural inequality. BAGs are
increased in MCI and dementia groups, particularly in posterior cortical regions. Structural inequality
emerges as the strongest predictor of BAG, surpassing cognition, education, and sex. The findings
indicate that an α-oscillation-based brain clock provides a sensitive functional marker of brain aging,
capable of capturing neurodegenerative processes as well as the impact of social disparities. This
scalable, accessible approach to brain health shows promise for translational use and populationwide screening in underserved, resource-limited settings.
