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Speech-based digital cognitive assessment for clinical trials: Detecting cognitive impairment stages and AD biomarker relations across European cohorts

Alexandra König, Johannes Tröger, Elisa Mallick, Nicklas Linz, Craig Ritchie, Sarah Gregory, Matthew Hunter, Kay Johnson, Gonzalo Sánchez Benavides, Oriol Grau-Rivera, Andreea Radoi, Claudia Porta-Mas, Stefanie Köhler, Stefan Teipel, Oskar Hansson, Pontus Tideman, Anika Wuestefeld, Sebastian Palmqvist 

Alzheimer’s & Dementia 2026.

Abstract

INTRODUCTION

Early detection of Alzheimer’s disease (AD) is critical for timely intervention as disease-modifying treatments emerge. Speech-based digital biomarkers offer scalable options for remotely capturing speech-derived functional changes associated with early cognitive decline, but validation across real-world populations remains limited.

METHODS

We evaluated the speech biomarker for cognition (SB-C), an automated speech-derived measure associated with cognitive status, in 736 participants across five European cohorts (Barcelonaβeta Brain Research Center’s Alzheimer’s at-risk cohort, European Prevention of Alzheimer’s Dementia Scotland, Dementia Study of Cognitive and Biomarker Dynamics, Longitudinal Cognitive Impairment and Dementia Study, and Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably [BioFINDER-Primary Care]). Participants completed verbal learning and semantic fluency tasks via automated phone or app-based platforms. SB-C performance was compared to Mini-Mental State Examination, Clinical Dementia Rating, Preclinical Alzheimer Cognitive Composite 5, and cerebrospinal fluid amyloid beta and phosphorylated tau181 biomarker status.

RESULTS

SB-C significantly differentiated cognitively unimpaired and impaired groups (P < 0.001), correlated with standard cognitive measures, and showed moderate-to-high area under the curve (0.56–0.82) for classifying biomarker positivity, with strongest results in BioFINDER-Primary Care.

DISCUSSION

SB-C is a scalable, remote speech-derived marker associated with cognitive status and AD biomarker group differences.

Highlights

  • The speech biomarker for cognition (SB-C) detects early Alzheimer’s disease (AD)-related cognitive impairment remotely.
  • The SB-C was validated across five European cohorts with diverse cognitive and biomarker profiles.
  • SB-C scores associated with cerebrospinal fluid amyloid beta and phosphorylated tau181 biomarker positivity.
  • Significant differences were observed in cognitively unimpaired individuals with subjective cognitive decline by amyloid/tau status.
  • SB-C supports scalable screening for AD in decentralized clinical trial settings.

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