Listening for Alzheimer’s clues: machine learning analysis of multidomain speech features for cognitive impairment screening

IntroductionEarly detection of Alzheimer’s disease (AD) is critical for timely intervention, particularly during the mild cognitive impairment (MCI) stage. This study aimed to develop and evaluate a multidomain speech analysis framework to support cognitive screening, biomarker prediction within the amyloid, tau and neurodegeneration (ATN) framework, and estimation of cognitive function across the AD continuum.MethodsThis study analyzed speech from 2,320 individuals spanning the cognitive spectrum-including those with subjective cognitive decline (SCD), MCI, and Alzheimer’s disease dementia (ADD)-using three spoken tasks (∼3 min) and extracted multidomain features including acoustic, lexical, syntactic, and semantic features. Machine learning models were trained to classify cognitive status, predict amyloid, tau and neurodegeneration (ATN) biomarker positivity, and estimate scores across six neuropsychological domains.ResultsMultidomain speech models achieved high performance in differentiating cognitive stages, with AUC values of up to 0.94 for SCD vs. ADD and 0.82 for SCD vs. MCI classifications. In biomarker prediction, the models yielded AUCs of 0.71, 0.74, and 0.73 for ATN classification, respectively. Speech-based models also showed strong correlations (up to 0.83) with cognitive function scores. Feature importance analysis revealed that verbal fluency measures were the most predictive. Explainability analyses indicated minimal dependency on age, sex, or education, supporting model fairness.DiscussionThese findings show that multidomain speech features capture clinically and biologically relevant information across the AD continuum, enabling cognitive classification, biomarker prediction, and cognitive estimation. These results underscore the potential of speech analysis as a non-invasive, accessible tool for scalable cognitive screening and early detection of AD. These results underscore the potential of speech analysis as a non-invasive, accessible tool for scalable cognitive screening and early detection of AD.