Spoken Discourse Biomarker of PD Cognitive Impairment

Study Overview
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Brief Summary
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The purpose of this study is to identify unique profiles of speech and language changes that distinguish individuals with Parkinson's disease from adults without Parkinson's disease and individuals with Parkinson's disease with cognitive (e.g., memory, thinking skills) impairment from those without cognitive impairment.

Detailed Description
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Aim 1 will characterize PD-MCI (Parkinson's disease mild cognitive impairment), PDN (Parkinson's disease without cognitive impairment), and HA (healthy adult) spoken discourse, cognitive, and motor speech profiles. Phase 2 biomarker development requires robustly characterized cohorts in which to test candidate biomarkers. Using a standardized battery of cognitive, language, and motor speech tests PD participants will be assigned to PD-MCI (single/multi-domain) or PDN groups. The investigators propose collecting spoken discourse samples using standardized elicitation protocols. The same tasks will be extracted from the extant HA database. Researchers will transcribe, code, and analyze discourse samples. Group differences (including sub-analyses for single and multi-domain MCI subtypes), elicitation stimuli effects, and group x stimuli interactions will be examined using multivariate and mixed-design ANOVA procedures. Aim 2 will develop and evaluate the classification accuracy of an optimally weighted discourse classification function for PD-MCI and PDN. The investigators propose using discriminant function analysis to identify an optimized composite variable that best predicts PD-MCI, PDN, and HA group membership. Sensitivity/specificity analyses, positive/negative predictive values, and receiver operating characteristic curves will be used to evaluate the discourse classification function properties. The primary endpoint is an optimally weighted discourse function that can classify PD-MCI with > 80% sensitivity/specificity.

Official Title
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Spoken Language Biomarker of Cognitive Impairment in PD

Conditions
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Parkinson Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only individuals with PD will be newly recruited and enrolled as part of the study. Healthy adult data will be extracted from extant databases (publicly available) from NIH-funded studies. Inclusion Criteria Person with Parkinson's disease without cognitive impairment Age 50-90 years Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria) made by a movement disorders specialist Under the care of a movement disorders specialist for a minimum of 1-year duration Native monolingual English speaker Hoehn & Yahr score between 1.5 and 4 Grade 10 education, or higher Sufficient vision and hearing (aided or unaided) for all experiment tasks Montreal Cognitive Assessment (or MoCA-converted MMSE score) greater than or equal to 25 No subjective complaints of cognitive difficulty or word finding issues Inclusion Criteria Person with Parkinson's disease mild cognitive impairment Age 50-90 years Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria) made by a movement disorders specialist Under the care of a movement disorders specialist for a minimum of 1-year duration Native monolingual English speaker Hoehn & Yahr score between 1.5 and 4 Grade 10 education, or higher Sufficient vision and hearing (aided or unaided) for all experiment tasks Montreal Cognitive Assessment (or MoCA-converted MMSE score) greater than or equal to 17 Subjective complaints of cognitive difficulty or word finding issues, without significant impact on activities of daily living Inclusion Healthy Adults (from extant data base - no new recruiting) Age 50-90 years Montreal Cognitive Assessment (or MoCA-converted MMSE score) greater than or equal to 26 Native monolingual English speaker Grade 10 education, or higher Sufficient vision and hearing (aided or unaided) for all experiment tasks Exclusion Criteria: Exclusion Criteria Neurological injury or disease (other than PD for the PD cohort) History of unmanaged or untreated depression or major psychiatric illness History of deep brain stimulation surgery (DBS) Diagnosis of Dementia with Lewy Bodies

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pakinson's disease without cognitive impairment<br>Age 50-90 years Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria) made by a movement disorders specialist Under the care of a movement disorders specialist for a minimum of 1-year duration Native monolingual English speaker Hoehn & Yahr score between 1.5 and 4 Grade 10 education, or higher Sufficient vision and hearing (aided or unaided) for all experiment tasks Montreal Cognitive Assessment (or MoCA-converted MMSE score) greater than or equal to 25 No subjective complaints of cognitive difficulty or word finding issues | |
| Pakinson's disease with cognitive impairment<br>Age 50-90 years Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria) made by a movement disorders specialist Under the care of a movement disorders specialist for a minimum of 1-year duration Native monolingual English speaker Hoehn & Yahr score between 1.5 and 4 Grade 10 education, or higher Sufficient vision and hearing (aided or unaided) for all experiment tasks Montreal Cognitive Assessment (or MoCA-converted MMSE score) greater than or equal to 17 Subjective complaints of cognitive difficulty or word finding issues, without significant impact on activities of daily living | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discourse Composite Variable | Weighted variable comprised of discourse features extracted from spoken discourse samples across productivity, lexical retrieval, verbal fluency, syntax complexity, grammatical accuracy, narrative coherence, correct information units, and main event accuracy. Raw data from each measure are multiplied by a specified weight and summed to generate a single composite discourse score. | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Words per minute | Number of total words ÷ Participant speaking time in minutes | baseline | 
| Correct information units (CIUs) | Number of words intelligible in context and accurate, relevant, and informative about the picture content (Brookshire & Nicholas, 1994; Nicholas & Brookshire, 1993) | baseline | 
| % CIUs | CIUs ÷ number of words (Brookshire & Nicholas, 1994; Nicholas & Brookshire, 1993) × 100 | baseline | 
| CIUs/min | CIUs ÷ Participant speaking time in minutes (Brookshire & Nicholas, 1994; Nicholas & Brookshire, 1993) | baseline | 
| % Main Events | Proportion of correct narrative main events (Capilouto et al., 2005) | baseline | 
| Moving-average type-token ratio (MATTR) | SALT-generated moving-average ratio of different words : total words (SALT Inc., 2017). Window size = 23 words, based on the number of words in smallest discourse sample (Roberts & Post, 2018) | baseline | 
| Mean length of utterance (MLU) | Mean length of utterance in words for intelligible, complete, verbal, task-relevant utterances (SALT Inc., 2017) | baseline | 
| % Grammatical | Number of content units without lexical selection or grammar rule violations (Thompson et al., 1995, 2012) ÷ Total intelligible, complete, verbal, task-relevant utterances × 100 | baseline | 
| Subordination index (SI) | Subordination index composite score. The ratio of total number of subject + Predicate clauses : total number of content units (SALT Software LLC, 2018b) | baseline | 
| Number of clauses/content units | Number of clauses per content units (based on the count of main verbs) | baseline | 
| Word-level dysfluencies/content units | Total number of word, syllable, and sound repetitions plus the total number of initial, middle, and final sound prolongations (SALT Software LLC, 2018a) ÷ Total utterances | baseline | 
| Number of pauses/content units | Number of pauses >1.5 s ÷ Total utterances | baseline | 
| Percent maze words/total words | Maze words (i.e., filled pauses, false starts, reformulations, and interjections) ÷ Maze words + non-maze words | baseline |