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. 2025 Dec 24;21(Suppl 3):e098534. doi: 10.1002/alz70857_098534

Leveraging Digital Speech Features for Early Identification of Alzheimer's Disease: Associations with structural and functional brain changes over time

Qingyue Li 1,, Stefanie Köhler 2, Alexandra König 3,4, Martin Dyrba 2, Zampeta‐Sofia Alexopoulou 4, Elisa Mallick 3, Nicklas Linz 3, Anja Schneider 5,6, Annika Spottke 7,8, Björn Falkenburger 9,10, Christoph Laske 11,12, Emrah Düzel 13,14, Frank Jessen 6,15,16, Inga Zerr 17,18, Jens Wiltfang 19,20,21, Josef Priller 22,23,24,25, Luca Kleineidam 5,6, Melina Stark 5,6, Michael Wagner 5,6, Gabor C Petzold 26,27, Fedor Levin 2, Stefan Teipel 1,2
PMCID: PMC12738232

Abstract

Background

Speech features extracted from automated remote cognitive assessments correlate with performance on traditional cognitive tasks in individuals at risk of Alzheimer's Disease (AD), demonstrating their potential to support early diagnosis. However, the capability of these features to signal early AD‐related brain changes remains less explored.

Method

Within the PROSPECT‐AD study, 234 participants ranging from cognitively normal to mild cognitive impairment were recruited from the German DZNE longitudinal cohorts DELCODE and DESCRIBE. At home, all participants completed the phone‐based and chatbot‐guided Semantic Verbal Fluency task (SVF) and the Rey Auditory Verbal Learning Test (RAVLT). Linguistic and acoustic features were automatically extracted from phone call recordings using an AI model to calculate task‐specific and composite cognitive scores. Structural MRI, functional MRI, and various paper‐and‐pencil cognitive scores were collected during cohort visits. We employed multiple linear regression, mixed‐effects models, and independent component analysis (ICA), followed by voxel‐wise post hoc analyses, to assess associations between digital speech‐based indicators and: (1) cross‐sectional brain atrophy (n = 108), (2) longitudinal brain atrophy (n = 90), (3) cross‐sectional resting‐state functional connectivity (n = 86), and additionally (4) trajectories of cognitive decline (n = 146).

Result

SVF correct counts were positively associated with brain volumes in the left temporal pole, left inferior, middle, and superior temporal gyri (The t(100) values ranged from 4.48 to 4.96) in voxel‐wise analyses (Figure 1a). Longitudinal analyses indicated that higher SVF correct counts were linked to slower rates of hippocampal and anterior cingulate atrophy (Figure 1b). Functional connectivity analyses suggested that SVF features, such as word frequency, were associated with rsFC areas within the default mode network (The t(71) values ranged from 3.65 to 3.85) (Figure 1c). Higher composite cognitive scores, along with SVF and RAVLT features, were associated with slower cognitive decline, as measured by established paper‐and‐pencil cognitive assessments, including the Preclinical Alzheimer Cognitive Composite (PACC) 5, SVF, and RAVLT delayed recall (Figure 2).

Conclusion

Phone‐based cognitive assessments hold promise as a remote and scalable tool for identifying AD‐related structural and functional brain changes. They offer predictive value for cognitive trajectories in pre‐dementia populations. This approach could aid in identifying individuals at risk while guiding further evaluation, broadening their utility beyond cognitive screening.


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Articles from Alzheimer's & Dementia are provided here courtesy of Wiley

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