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

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.

Detecting subtle signs of depression with automated speech analysis in a non-clinical sample.

BACKGROUND: Automated speech analysis has gained increasing attention to help diagnosing depression. Most previous studies, however, focused on comparing speech in patients with major depressive disorder to that in healthy volunteers. An alternative may be to associate speech with depressive symptoms in a non-clinical sample as this may help to find early and sensitive markers in those at risk of depression. METHODS: We included n = 118 healthy young adults (mean age: 23.5 ± 3.7 years; 77% women) and asked them to talk about a positive and a negative event in their life. Then, we assessed the level of depressive symptoms with a self-report questionnaire, with scores ranging from 0-60. We transcribed speech data and extracted acoustic as well as linguistic features. Then, we tested whether individuals below or above the cut-off of clinically relevant depressive symptoms differed in speech features. Next, we predicted whether someone would be below or above that cut-off as well as the individual scores on the depression questionnaire. Since depression is associated with cognitive slowing or attentional deficits, we finally correlated depression scores with performance in the Trail Making Test. RESULTS: In our sample, n = 93 individuals scored below and n = 25 scored above cut-off for clinically relevant depressive symptoms. Most speech features did not differ significantly between both groups, but individuals above cut-off spoke more than those below that cut-off in the positive and the negative story. In addition, higher depression scores in that group were associated with slower completion time of the Trail Making Test. We were able to predict with 93% accuracy who would be below or above cut-off. In addition, we were able to predict the individual depression scores with low mean absolute error (3.90), with best performance achieved by a support vector machine. CONCLUSIONS: Our results indicate that even in a sample without a clinical diagnosis of depression, changes in speech relate to higher depression scores. This should be investigated in more detail in the future. In a longitudinal study, it may be tested whether speech features found in our study represent early and sensitive markers for subsequent depression in individuals at risk.

Patients with amnestic MCI Fail to Adapt Executive Control When Repeatedly Tested with Semantic Verbal Fluency Tasks.

OBJECTIVE: Semantic verbal fluency (SVF) tasks require individuals to name items from a specified category within a fixed time. An impaired SVF performance is well documented in patients with amnestic Mild Cognitive Impairment (aMCI). The two leading theoretical views suggest either loss of semantic knowledge or impaired executive control to be responsible. METHOD: We assessed SVF 3 times on 2 consecutive days in 29 healthy controls (HC) and 29 patients with aMCI with the aim to answer the question which of the two views holds true. RESULTS: When doing the task for the first time, patients with aMCI produced fewer and more common words with a shorter mean response latency. When tested repeatedly, only healthy volunteers increased performance. Likewise, only the performance of HC indicated two distinct retrieval processes: a prompt retrieval of readily available items at the beginning of the task and an active search through semantic space towards the end. With repeated assessment, the pool of readily available items became larger in HC, but not patients with aMCI. CONCLUSION: The production of fewer and more common words in aMCI points to a smaller search set and supports the loss of semantic knowledge view. The failure to improve performance as well as the lack of distinct retrieval processes point to an additional impairment in executive control. Our data did not clearly favour one theoretical view over the other, but rather indicates that the impairment of patients with aMCI in SVF is due to a combination of both.