Preprint: Detecting Preclinical Alzheimer’s Disease Risk in Cognitively Normal Adults Using Speech Acoustics: Validation with Plasma p-Tau217 and APOE-ε4 Status
Authors: Mehrdad Dadgostar, Lindsay C. Hanford, Maryam Tavakoli, Steven E. Arnold, David H. Salat, Tatiana Sitnikova, Pia Kivisakk Webb, Jordan R. Green, Hengru Liu, Brian D. Richburg, Mariam Tkeshelashvili, Marziye Eshghi Abstract INTRODUCTION We tested whether spontaneous speech acoustics provide a scalable digital marker of biologically defined Alzheimer’s disease (AD) risk. METHODS Forty-nine cognitively unimpaired older adults were stratified within APOE genotype into Low-, Moderate-, and High-Risk groups based on log₁₀-transformed plasma p-tau217. Acoustic features were extracted from spontaneous speech and entered into multiclass SVM classifiers with leave-one-out cross-validation, with and without genetic-algorithm feature selection and age. Parallel models using neuropsychological measures were evaluated for comparison. Feature contributions were interpreted using SHAP. RESULTS Speech-based models substantially outperformed cognition-only models and exceeded chance performance for three-group classification (33.3%), achieving up to 77% accuracy compared with 47%…