Speech clocks decode dementia phenotypes, social exposome, and biological aging.
Biological 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.
Authors
Hernandez Hernandez, Pedraza Pedraza, Santamaria-Garcia Santamaria-Garcia, Moguilner Moguilner, Legaz Legaz, Prado Prado, Cuadros Cuadros, Amoruso Amoruso, Gonzalez Gonzalez, Dellavale Dellavale, Espinoza-Puelles Espinoza-Puelles, Espinosa Espinosa, Jarne Jarne, Mattiussi Mattiussi, Caccia Caccia, Welford Welford, Pelella Pelella, Inchauspe Inchauspe, Ferrante Ferrante, PĂ©rez PĂ©rez, Maito Maito, Rocatti Rocatti, Godoy Godoy, Migeot Migeot, Orellana Orellana, Caviedes Caviedes, Bruno Bruno, Takada Takada, Slachevsky Slachevsky, Behrens Behrens, Bruna Bruna, Aguillon Aguillon, Zapata Zapata, Avila-Funes Avila-Funes, Custodio Custodio, Miller Miller, Gorno-Tempini Gorno-Tempini, Escudero Escudero, Reyes Reyes, Hu Hu, de Oliveira de Oliveira, Coronel-Oliveros Coronel-Oliveros, Cruzat Cruzat, Cardona Cardona, Corley Corley, Meier Meier, Narayan Narayan, Tagliazucchi Tagliazucchi, Baez Baez, Duran-Aniotz Duran-Aniotz, GarcĂa GarcĂa, Ibanez Ibanez
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