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. 2022 Sep 30;6(3):107-116.
doi: 10.1159/000526471. eCollection 2022 Sep-Dec.

Validation of the Remote Automated ki:e Speech Biomarker for Cognition in Mild Cognitive Impairment: Verification and Validation following DiME V3 Framework

Johannes Tröger  1 , Ebru Baykara  1 , Jian Zhao  1 , Daphne Ter Huurne  2 , Nina Possemis  2 , Elisa Mallick  1 , Simona Schäfer  1 , Louisa Schwed  1 , Mario Mina  1 , Nicklas Linz  1 , Inez Ramakers  2 , Craig Ritchie  3
Affiliations

Validation of the Remote Automated ki:e Speech Biomarker for Cognition in Mild Cognitive Impairment: Verification and Validation following DiME V3 Framework

Johannes Tröger et al. Digit Biomark. .

Abstract

Introduction: Progressive cognitive decline is the cardinal behavioral symptom in most dementia-causing diseases such as Alzheimer's disease. While most well-established measures for cognition might not fit tomorrow's decentralized remote clinical trials, digital cognitive assessments will gain importance. We present the evaluation of a novel digital speech biomarker for cognition (SB-C) following the Digital Medicine Society's V3 framework: verification, analytical validation, and clinical validation.

Methods: Evaluation was done in two independent clinical samples: the Dutch DeepSpA (N = 69 subjective cognitive impairment [SCI], N = 52 mild cognitive impairment [MCI], and N = 13 dementia) and the Scottish SPeAk datasets (N = 25, healthy controls). For validation, two anchor scores were used: the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) scale.

Results: Verification: The SB-C could be reliably extracted for both languages using an automatic speech processing pipeline. Analytical Validation: In both languages, the SB-C was strongly correlated with MMSE scores. Clinical Validation: The SB-C significantly differed between clinical groups (including MCI and dementia), was strongly correlated with the CDR, and could track the clinically meaningful decline.

Conclusion: Our results suggest that the ki:e SB-C is an objective, scalable, and reliable indicator of cognitive decline, fit for purpose as a remote assessment in clinical early dementia trials.

Keywords: Clinical trials; Dementia; Digital biomarker; Mild cognitive impairment; Speech analysis; Speech biomarker.

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Conflict of interest statement

Daphne ter Huurne, Nina Possemis, and Inez Ramakers have no conflicts of interest. Johannes Tröger, Ebru Baykara, Jian Zhao, Elisa Mallick, Simona Schäfer, Louisa Schwed, Mario Mina, and Nicklas Linz are employees of the digital biomarker company ki elements. Johannes Tröger and Nicklas Linz hold shares of the digital biomarker company ki elements. Craig Ritchie has received consultancy fees from Biogen, Eisai, MSD, Actinogen, Roche, and Eli Lilly, as well as payment or honoraria from Roche and Eisai.

Figures

Fig. 1
Fig. 1
Conceptual framework connecting the meaningful aspect of health in dementia patients with the SB ki:e SB-C.
Fig. 2
Fig. 2
a Schematic representation of the processing steps involved in collecting and calculating the ki:e SB-C. b Schematic representation of the structure and development of the ki:e SB-C and its domain scores.
Fig. 3
Fig. 3
Partial correlation between ki:e SB-C global biomarker score and MMSE total score, controlling for age.
Fig. 4
Fig. 4
a Group difference in ki:e SB-C score between diagnostic groups at DeepSpA T0, controlling for age. b Partial correlation between ki:e SB-C score and CDR-SOB at DeepSpA T0, controlling for age.
Fig. 5
Fig. 5
SB-C score differences (∆[SB-C_T12 − SB-C_T0]) between decliners and non-decliners. Those participants with a positive CDR difference (CDR_T12 − CDR_T0 = 0.5) are considered decliners as their CDR score increased in T12 as compared to T0.
See this image and copyright information in PMC

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