Abstract
INTRODUCTION: Advances in natural language processing (NLP), speech recognition, and machine learning (ML) allow the exploration of linguistic and acoustic changes previously difficult to measure. We developed processes for deriving lexical-semantic and acoustic measures as Alzheimer's disease (AD) digital voice biomarkers. METHODS: We collected connected speech, neuropsychological, neuroimaging, and cerebrospinal fluid (CSF) AD biomarker data from 92 cognitively unimpaired (40 Aβ+) and 114 impaired (63 Aβ+) participants. Acoustic and lexical-semantic features were derived from audio recordings using ML approaches. RESULTS: Lexical-semantic (area under the curve [AUC] = 0.80) and acoustic (AUC = 0.77) scores demonstrated higher diagnostic performance for detecting MCI compared to Boston Naming Test (AUC = 0.66). Only lexical-semantic scores detected amyloid-β status (p = 0.0003). Acoustic scores associated with hippocampal volume (p = 0.017) while lexical-semantic scores associated with CSF amyloid-β (p = 0.007). Both measures were significantly associated with 2-year disease progression. DISCUSSION: These preliminary findings suggest that derived digital biomarkers may identify cognitive impairment in preclinical and prodromal AD, and may predict disease progression. HIGHLIGHTS: This study derived lexical-semantic and acoustics features as Alzheimer's disease (AD) digital biomarkers.These features were derived from audio recordings using machine learning approaches.Voice biomarkers detected cognitive impairment and amyloid-β status in early stages of AD.Voice biomarkers may predict Alzheimer's disease progression.These markers significantly mapped to functional connectivity in AD-susceptible brain regions.