Source-space EEG alpha activity reveals brain age gaps due to neurodegeneration and disparity

Authors: Otero M, Carriel-Rubilar FI, Hernandez H, Cuadros J, Condado JG, Sainz-Ballesteros A, Santamaria-Garcia H, Legaz A, Birba A, Fittipaldi S, Lopera F, Ochoa-Gómez J, Aguillon D, González-Hernández A, Bonilla-Santos J, Gonzalez-Montealegre RA, Yener GG, Güntekin B, Kıyı İ, Aktürk T, Yıldırım E, Hanoğlu L, Anghinah R, Valdes-Sosa PA, Garcia-Reyes R, Escudero J, Lopez S, Whelan R, Fernández A, García AM, Huepe D, Soto-Añari M, Herrera E, Abasolo D, Rubido N, Clark RA, El-Deredy W, Cortes JM, Parra MA, Babiloni C, Ibanez A, Prado P

Abstract: 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 age-related 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 population-wide screening in underserved, resource-limited settings.