Harnessing acoustic speech parameters to decipher amyloid status in individuals with mild cognitive impairment

Front Neurosci. 2023 Sep 7:17:1221401. doi: 10.3389/fnins.2023.1221401. eCollection 2023.

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of mild cognitive impairment (MCI) to enable early interventions. Among the neuropathological events associated with the onset of the disease is the accumulation of amyloid protein in the brain, which correlates with decreased levels of Aβ42 peptide in the cerebrospinal fluid (CSF). Consequently, the development of non-invasive, low-cost, and easy-to-administer proxies for detecting Aβ42 positivity in CSF becomes particularly valuable. A promising approach to achieve this is spontaneous speech analysis, which combined with machine learning (ML) techniques, has proven highly useful in AD. In this study, we examined the relationship between amyloid status in CSF and acoustic features derived from the description of the Cookie Theft picture in MCI patients from a memory clinic. The cohort consisted of fifty-two patients with MCI (mean age 73 years, 65% female, and 57% positive amyloid status). Eighty-eight acoustic parameters were extracted from voice recordings using the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS), and several ML models were used to classify the amyloid status. Furthermore, interpretability techniques were employed to examine the influence of input variables on the determination of amyloid-positive status. The best model, based on acoustic variables, achieved an accuracy of 75% with an area under the curve (AUC) of 0.79 in the prediction of amyloid status evaluated by bootstrapping and Leave-One-Out Cross Validation (LOOCV), outperforming conventional neuropsychological tests (AUC = 0.66). Our results showed that the automated analysis of voice recordings derived from spontaneous speech tests offers valuable insights into AD biomarkers during the preclinical stages. These findings introduce novel possibilities for the use of digital biomarkers to identify subjects at high risk of developing AD.

Keywords: Alzheimer's disease; automated pattern recognition; biomarkers; cerebrospinal fluid; early diagnosis; machine learning; mild cognitive impairment; speech acoustics.

Grants and funding

This project has received funding from R&D Missions in the Artificial Intelligence program, which is part of the Spain Digital 2025 Agenda and the National Artificial Intelligence Strategy and financed by the European Union through Next Generation EU funds (project TARTAGLIA, exp. MIA.2021.M02.0005). This project has also received funding from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER–Una manera de hacer Europa) grant PI19/00335 awarded to MM, grant PI17/01474 awarded to MB, grants AC17/00100, PI19/01301, and PI22/01403 awarded to AR and by the European Union Joint Programme–Neurodegenerative Disease Research (JPND) Multinational research projects on Personalized Medicine for Neurodegenerative Diseases/Instituto de Salud Carlos III grant AC19/00097 awarded to AR and grant FI20/00215 from the Instituto de Salud Carlos III (ISCIII) awarded to IR. For CSF biomarker research, AR and MB received support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). AC received support from the Instituto de Salud Carlos III (ISCIII) under the grant Sara Borrell (CD22/00125) and the Spanish Ministry of Science and Innovation, Proyectos de Generación de Conocimiento grant PID2021-122473OA-I00.