Speech clocks decode dementia phenotypes, social exposome, and biological aging
Hernan Hernandez, Lizeth Katherine Pedraza, Hernando Santamaria-Garcia, Sebastian Moguilner, Agustina Legaz, Pavel Prado, Jhosmary Cuadros, Lucía Amoruso, Liset Gonzalez, Damián Dellavale, Juan Pablo Espinoza–Puelles, Javier Palma Espinosa, Cecilia Jarne, Fabio Mattiussi, Matías Caccia, Alejandro Sosa Welford, Nicolás Pelella, Jeremías Inchauspe, Franco J. Ferrante, Gonzalo Pérez, Marcelo Adrián Maito, Guido Rocatti, Maria Eugenia Godoy, Joaquin Migeot, Paulina Orellana, Ariel Caviedes, Martin Bruno, Leonel Takada, Andrea Slachevsky, Maria I Behrens, Bárbara Bruna, David Aguillon, Lina Zapata, Jose Alberto Avila-Funes, Nilton Custodio, Bruce Miller, Maria Luisa Gorno-Tempini, Stefanie Pina Escudero, Pablo Reyes, Kun Hu, Maira Okada de Oliveira, Carlos Coronel-Oliveros, Josephine Cruzat, Juan Felipe Cardona, Michael Corley, Irene B. Meier, Vaibhav A. Narayan, Enzo Tagliazucchi, Sandra Baez, Claudia Duran-Aniotz, Adolfo M. García, Agustin IbanezBiological aging clocks offer estimations of aging and dementia, yet scalability is limited. We introduce a large-scale, cross-national speech clock derived from 2928 individuals across five Latin American countries, spanning healthy controls (HCs), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and non-language/language-dominant frontotemporal dementia (nldFTD/ldFTD). Multimodal acoustic and linguistic features were trained with supervised models to estimate chronological age, generating speech age gaps (SAGs) as cross-sectional markers of deviations from chronological age, with positive values interpreted as relatively older-appearing speech profiles. SAGs differentiated diagnostic groups (HCs < patient groups, with AD < nldFTD < ldFTD). This pattern was associated with clinical/cognitive domains. SAGs correlated with phosphorylated tau (p-Tau217) in AD and social exposome in HCs and AD. Brain clocks (structural/functional/combined) were associated with SAG in AD, nldFTD, and ldFTD. Epigenetic age correlated with SAGs in HCs and AD across Hannum, Retroclock, and OMICmAge, whereas ldFTD associations were limited to Retroclock and OMICmAge. These results indicate that SAGs capture cross-sectional multilevel aging-related variation and may offer a scalable, culturally adaptable, low-cost biomarker candidate for research in underrepresented global settings.