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Benchmarking speech biomarkers of Alzheimer's against cognitive and neural measures

Caro I, Pérez G, Bize JV, Ponferrada J, Ferrante FJ, Welford AS, Gauder L, Olavarría L, Henríquez F, Ramos T, Besnier C, Ferrer L, Gorno-Tempini ML, Slachevsky A, Ibañez A, García AM

Abstract

Introduction: Digital speech biomarkers (DSBs) support the detection and monitoring of Alzheimer's disease (AD) in Latinos. However, they have not been benchmarked against standard cognitive and neuroimaging measures, missing a critical validation milestone.

Methods: Thirty-three AD patients and 33 healthy controls completed verbal fluency tasks, episodic memory and executive tests, and magnetic resonance imaging (MRI) (volume) and functional MRI (fMRI) (connectivity) scans. Between-group machine learning classification was compared among fluency-derived DSBs, episodic and executive test scores, MRI, and fMRI measures.

Results: The fluency classifier's performance (area under the curve [AUC] = 0.84) was comparable (p > 0.14) to the episodic (AUC = 0.90), executive (AUC = 0.79), and structural (AUC = 0.90) classifiers and superior to the functional classifier (AUC = 0.65, p = 0.002). Top discriminating features were word length and frequency, both associated with right (pre)frontal volume upon adjusting for sociodemographic factors.

Discussion: DSBs appear non-inferior to standard cognitive and imaging measures, supporting scalable AD assessments in Latinos.

Highlights: We examined digital speech biomarkers (DSBs) for detecting AD in Latinos. DSBs were benchmarked against cognitive and neuroimaging features. DSB-based classifiers matched or outperformed cognitive and brain classifiers. Top DSBs included word length, phonological neighborhood, and frequency. Word length and frequency correlated with right (pre)frontal brain volume.

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Reference

Caro I, Pérez G, Bize JV, Ponferrada J, Ferrante FJ, Welford AS, Gauder L, Olavarría L, Henríquez F, Ramos T, Besnier C, Ferrer L, Gorno-Tempini ML, Slachevsky A, Ibañez A, García AM. Benchmarking speech biomarkers of Alzheimer's against cognitive and neural measures. Alzheimers Dement. 2026 Apr;22(4):e71365. doi: 10.1002/alz.71365. PMID: 41979006; PMCID: PMC13077448.