Voice Acoustic Instability During Spontaneous Speech in Parkinson's Disease.

BACKGROUND: In people with Parkinson's disease (PwPD), both motor and cognitive deficits influence voice and other aspects of communication. PwPD demonstrate vocal instability, but acoustic declines over the course of speaking are not well characterized and the role of cognition on these declines is unknown. We examined voice acoustics related to speech motor instability by comparing the first and the last utterances within a speech task. Our objective was to determine if mild cognitive impairment (MCI) status was associated with different patterns of acoustic change during these tasks. METHODS: Participants with PD (n = 44) were enrolled at University of Massachusetts Chan Medical School and classified by gold-standard criteria as normal cognition (PD-NC) or mild cognitive impairment (PD-MCI). The speech was recorded during the Rainbow Passage and a picture description task (Cookie Theft). We calculated the difference between first and last utterances in fo mean and standardized semitones (STSD), cepstral peak prominence-smoothed (CPPS), and low to high ratio (LH). We used t-tests to compare the declines in acoustic parameters between the task types and between participants with PD-NC versus PD-MCI. RESULTS: Mean fo, fo variability (STSD) and CPPS declined from the first to the last utterance in both tasks, but there was no significant difference in these declines between the PD-NC and PD-MCI groups. Those with PD-MCI demonstrated lower fo variability on the whole in both tasks and lower CPPS in the picture description task, compared to those with PD-NC. CONCLUSIONS: Mean and STSD fo as well as CPPS may be sensitive to PD-MCI status in reading and spontaneous speech tasks. Speech motor instability can be observed in these voice acoustic parameters over brief speech tasks, but the degree of decline does not depend on cognitive status. These findings will inform the ongoing development of algorithms to monitor speech and cognitive function in PD.

Pausing before verb production is associated with mild cognitive impairment in Parkinson's disease.

Background: Cognitive dysfunction and communication impairment are common and disabling symptoms in Parkinson's Disease (PD). Action verb deficits occur in PD, but it remains unclear if these impairments are related to motor system dysfunction and/or cognitive decline. The objective of our study was to evaluate relative contributions of cognitive and motor dysfunction to action verb production in naturalistic speech of patients with PD. We proposed that pausing before action-related language is associated with cognitive dysfunction and may serve as a marker of mild cognitive impairment in PD. Method: Participants with PD (n = 92) were asked to describe the Cookie Theft picture. Speech files were transcribed, segmented into utterances, and verbs classified as action or non-action (auxiliary). We measured silent pauses before verbs and before utterances containing verbs of different classes. Cognitive assessment included Montreal Cognitive Assessment (MoCA) and neuropsychological tests to categorize PD participants as normal cognition (PD-NC) or mild cognitive impairment (PD-MCI) based on Movement Disorders Society (MDS) Task Force Tier II criteria. Motor symptoms were assessed using MDS-UPDRS. We performed Wilcoxon rank sum tests to identify differences in pausing between PD-NC and PD-MCI. Logistic regression models using PD-MCI as dependent variables were used to evaluate the association between pause variables and cognitive status. Results: Participants with PD-MCI demonstrated more pausing before and within utterances compared to PD-NC, and the duration of these pauses were correlated with MoCA but not motor severity (MDS-UPDRS). Logistic regression models demonstrated that pauses before action utterances were associated with PD-MCI status, whereas pauses before non-action utterances were not significantly associated with cognitive diagnosis. Conclusion: We characterized pausing patterns in spontaneous speech in PD-MCI, including analysis of pause location with respect to verb class. We identified associations between cognitive status and pausing before utterances containing action verbs. Evaluation of verb-related pauses may be developed into a potentially powerful speech marker tool to detect early cognitive decline in PD and better understand linguistic dysfunction in PD.

Effect of Levodopa Initiation on the Gut Microbiota in Parkinson's Disease.

Background: The impact of Levodopa on the gut microbiota of Parkinson's disease (PD) patients has not been sufficiently addressed. Methods: We conducted a longitudinal study to examine the impact of Levodopa initiation on the gut microbiota composition of 19 PD patients who had not previously been exposed to Levodopa. Patients provided two stool samples prior to and two samples 90 days after starting Levodopa. Motor impairment (MDS-UPDRS Part III), diet, and other patient characteristics were assessed. 16S rRNA gene amplicon sequencing was used to characterize the microbiota. We examined, cross-sectionally and longitudinally, the associations between Levodopa use and alpha and beta diversity and performed feature-wise, multivariate modeling to identify taxa associated longitudinally with Levodopa use and with improvement in motor function after Levodopa administration. Results: We did not observe significant differences in alpha or beta diversity before vs. after initiation of Levodopa. In longitudinal feature-wise analyses, at the genus level, no taxa were significantly associated with Levodopa use after false discovery rate (FDR) correction (q < 0.05). We observed a marginally lower relative abundance of bacteria belonging to Clostridium group IV in PD patients who experienced a medium or large improvement in motor impairment in response to Levodopa compared to those with a small response [ß = -0.64 (SE: 0.18), p-trend: 0.00015 p-FDR: 0.019]. Conclusions: In this study, Levodopa was not associated with changes in microbiota composition in this longitudinal analysis. The association between abundance of Clostridium group IV and short-term motor symptom response to Levodopa is preliminary and should be investigated in larger, longer-term studies, that include a control group.

Survey on Acceptance of Passive Technology Monitoring for Early Detection of Cognitive Impairment.

INTRODUCTION: Digital biomarkers may act as a tool for early detection of changes in cognition. It is important to understand public perception of technologies focused on monitoring cognition to better guide the design of these tools and inform patients appropriately about the associated risks and benefits. Health care systems may also play a role in the clinical, legal, and financial implications of such technologies. OBJECTIVE: To evaluate public opinion on the use of passive technology for monitoring cognition. METHODS: This was a one-time, Internet-based survey conducted in English and Spanish. RESULTS: Within the English survey distributed in the USA (n = 173), 58.1% of respondents would be highly likely to agree to passive monitoring of cognition via a smartphone application. Thirty-eight percent of those with a higher degree of experience with technology were likely to agree to monitoring versus 20% of those with less experience with technology (p = 0.003). Sixty-two percent of non-health-care professionals were likely to agree to monitoring versus 45% of health-care workers (p = 0.012). There were significant concerns regarding privacy (p < 0.01). We compared the surveys answered in Spanish in Costa Rica via logistic regression (n = 43, total n = 216), adjusting for age, education level, health-care profession, owning a smartphone, experience with technology, and perception of cognitive decline. Costa Rican/Spanish-speaking respondents were 7 times more likely to select a high probability of agreeing to such a technology (p < 0.01). English-speaking respondents from the USA were 5 times more likely to be concerned about the impact on health insurance (p = 0.001) and life insurance (p = 0.01). CONCLUSIONS: Understanding public perception and ethical implications should guide the design of digital biomarkers for cognition. Privacy and the health-care system in which the participants take part are 2 major factors to be considered. It is the responsibility of researchers to convey the ethical and legal implications of cognition monitoring.

Patient and Clinician Impressions of Cognitive Impairment in Parkinson's Disease.

We investigated patient and clinician impressions of cognitive impairment and whether they correlated with objective measures of cognitive impairment. Cognitive categorization, neuropsychological assessment scores, and Montreal Cognitive Assessment scores were documented at baseline, 3 years, and 7 years for 388 PD patients in the Parkinson's Progression Markers Initiative (PPMI). We found that both patient and clinician impressions of cognitive decline were significantly associated with gold-standard criteria for cognitive impairment to a similar degree. Both patient and clinician perspectives should be considered in determining cognitive status and should be followed up with diagnostic testing.

Medical-legal partnerships: 11 years' experience of providing acute legal advice for critically ill patients and their families.

BACKGROUND: Medical-legal partnerships integrate lawyers into health care to identify and address legal problems that can create and perpetuate disparities in health for patients and their families. They have previously been utilised for patients who are at high-risk of being disadvantaged such as the elderly, the disabled and those affected by chronic diseases. We have used a partnership to address the legal needs of patients with acute, critical illness including major trauma. METHOD: In 2007, a free, comprehensive legal advice service was established at University Hospital Southampton NHS Foundation Trust. The service is bound by strict guidelines which have been endorsed by NHS England. The legal service is specifically prevented from acting against the NHS. A retrospective analysis of the service over a period of 11 years was undertaken to look at the range of legal advice sought. Where a potential compensation claim against a third party was identified, the percentage of cases where the legal service was instructed was noted and the outcome for those cases was examined in further detail. RESULTS: Five hundred and fifty-one patients and or their families have been referred to the legal service. Of these, 343 had sustained major trauma. Over 2300 hours of free legal advice were provided on non-compensation issues, primarily related to welfare benefits, local authority assistance, obtaining power of attorney or seeking Deputyship from the Court of Protection and claims against existing insurance policies. Two hundred and seventy-five of the 551 patients (50%) were found to have a potential compensation claim against a third party. The legal service was instructed to pursue a claim in 82 cases. Interim payments of nearly £13 million were provided and £128 million of compensation has been awarded in 51 cases that have been settled. DISCUSSION: Medical-legal partnerships are well-established in the USA. We have demonstrated that in UK, there is a demand for early legal advice for patients who have sustained critical illness including major trauma. More data are required to identify the rehabilitation outcomes for patients who have received legal support. A similar medical-legal partnership should be considered at every acute NHS Trust.

Approaches to Recruitment of Postmenopausal Women for a Community-Based Study.

BACKGROUND: Few researchers have focused on the challenges of recruiting postmenopausal women for community-based research. Researchers have reported that multiple methods may be needed to recruit the required number of subjects. One contemporary approach to recruitment is use of Facebook. More studies are needed examining Facebook as a recruitment strategy. OBJECTIVE: The aim of the study was to examine which recruitment methods were most successful and cost-effective in recruiting postmenopausal women for a randomized controlled trial on bone loss. METHODS: Subjects were 276 postmenopausal women who had osteopenia and were within 5 years of menopause. Multiple methods were used to recruit women. To determine which methods were successful, women were asked how they learned about the study. Descriptive data were used to examine recruitment numbers as well as to determine the cost-effectiveness and enrollment efficiency of recruitment methods. RESULTS: Healthcare provider letters yielded the highest number of enrolled subjects (n = 58), followed by postcard mailings (n = 47), and Facebook posts (n = 44). Eleven subjects were referred by family and friends, five subjects were from newspaper or television, and two were from digital ads. Cost of recruitment per subject enrolled was highest with digital ads and postcard mailings. DISCUSSION: Recruitment could be more costly and time-consuming than anticipated. Recruitment using direct-targeted mailings, such as provider letters and postcards, was successful in our study and has been effective in previous studies reviewed. Facebook was successful for recruitment in our study and may continue to be useful for recruitment in the future, as the number of women accessing Facebook continues to increase.

Communication impairment in Parkinson's disease: Impact of motor and cognitive symptoms on speech and language.

Communication impairment is common in Parkinson's disease (PD) and may have both motor speech control and cognitive-linguistic underpinnings. The neurobiology of communication impairment in PD is poorly understood, and work is needed to disentangle the relative contributions of motor and cognitive dysfunction. In clinical practice, cognitive-linguistic impairments are often overlooked despite the large body of research on this topic in neurocognitive and linguistics literature. In this review, we will discuss the roles of motor speech changes, cognitive and linguistic impairment, and other related functions in the communication disabilities of individuals with PD. We will describe the various types of communication difficulties in PD and tools for measuring these symptoms. We will discuss specific deficits that may further understanding of the neurobiology of communication impairment in PD, including voice and speech acoustic changes, linguistic processing and production difficulties, and pausing. We will emphasize the importance of an interdisciplinary approach and the patient perspective on daily communication in guiding future research.

Evaluation of Linguistic Markers of Word-Finding Difficulty and Cognition in Parkinson's Disease.

Purpose: Early cognitive symptoms such as word-finding difficulty (WFD) in daily conversation are common in Parkinson's disease (PD), but studies have been limited by a lack of feasible, quantitative measures. Linguistic analysis, focused on pauses in speech, may yield markers of impairment of cognition and communication in PD. The objective of this study was to evaluate the relationship of linguistic markers in semistructured speech to WFD symptoms and cognitive function in PD. Method: Speech recordings of description of the Cookie Theft picture in 53 patients with PD without dementia and 23 elderly controls were analyzed with Praat software. Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005), category naming fluency, and confrontation naming tests were administered. Questionnaires rating WFD symptoms and cognitive instrumental activities of daily living were completed. We determined the relationships between (a) pause length and location, (b) MoCA score, and (c) WFD symptoms, using Pearson's correlations and multivariate regression models. Results: Compared with controls, patients with PD had more pauses within utterances as well as fewer words per minute and a lower percentage of well-formed sentences. Pauses within utterances differed significantly between PD-mild cognitive impairment and normal cognition (p < .001). Words per minute and percentage of well-formed sentences were predictive of MoCA in multivariate regression models. Pauses before verbs were associated with patient-reported severity of WFD symptoms (p = .006). Conclusions: Linguistic markers including pauses within utterances distinguish patients with PD with mild cognitive symptoms from elderly controls. These markers are associated with global cognitive function before the onset of dementia. Pauses before verbs and grammatical markers may index early cognitive symptoms such as WFD that may interfere with functional communication. Supplemental Material: https://doi.org/10.23641/asha.6615401.

Incident impulse control disorder symptoms and dopamine transporter imaging in Parkinson disease.

OBJECTIVE: To describe the incidence of, and clinical and neurobiological risk factors for, new-onset impulse control disorder (ICD) symptoms and related behaviours in early Parkinson disease (PD). METHODS: The Parkinson's Progression Markers Initiative is an international, multicenter, prospective study of de novo patients with PD untreated at baseline and assessed annually, including serial dopamine transporter imaging (DAT-SPECT) and ICD assessment (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease short form, QUIP). Participants were included if they screened negative on the QUIP at baseline. Kaplan-Meier curves and generalised estimating equations examined frequency and predictors of incident ICD symptoms. RESULTS: Participants were seen at baseline (n=320), year 1 (n=284), year 2 (n=217) and year 3 (n=96). Estimated cumulative incident rates of ICD symptoms and related behaviours were 8% (year 1), 18% (year 2) and 25% (year 3) and increased each year in those on dopamine replacement therapy (DRT) and decreased in those not on DRT. In participants on DRT, risk factors for incident ICD symptoms were younger age (OR=0.97, p=0.05), a greater decrease in right caudate (OR=4.03, p=0.01) and mean striatal (OR=6.90, p=0.04) DAT availability over the first year, and lower right putamen (OR=0.06, p=0.01) and mean total striatal (OR=0.25, p=0.04) DAT availability at any post-baseline visit. CONCLUSIONS: The rate of incident ICD symptoms increases with time and initiation of DRT in early PD. In this preliminary study, a greater decrease or lower DAT binding over time increases risk of incident ICD symptoms, conferring additional risk to those taking DRT. CLINICAL TRIAL REGISTRATION: NCT01141023.

Uncommon applications of deep brain stimulation in hyperkinetic movement disorders.

BACKGROUND: In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS) has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS) and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study. METHODS: A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus. RESULTS: We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi) DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies. DISCUSSION: Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.

Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability.

IMPORTANCE: Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. OBJECTIVE: To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. DESIGN, SETTING, AND PARTICIPANTS: The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in which patients were randomized to rasagiline (1 or 2 mg/d) or placebo. MAIN OUTCOMES AND MEASURES: We evaluated the change in NMSs in patients taking an antidepressant and rasagiline compared with those taking placebo. The NMSs were assessed by Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Nonmotor Experiences of Daily Living, the original Unified Parkinson's Disease Rating Scale, and the Parkinson Fatigue Scale. RESULTS: A total of 191 of the 1174 patients (16.3%) were treated with antidepressants during phase 1 and provided efficacy data. Depression and cognition scores revealed significantly less worsening in the rasagiline group compared with the placebo group (differences in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale item-adjusted means [SEs], -0.19 [0.10], P = .048, and -0.20 [0.05], P < .001, respectively). Parkinson Fatigue Scale (mean [SE] difference, -0.42 [0.09], P < .001) and daytime sleepiness (mean [SE] difference, -0.24 [0.09], P = .006) scores also revealed significantly less worsening in the rasagiline group compared with placebo. There was a nonsignificant trend toward less worsening in apathy and no significant between-group differences in anxiety or sleep. The effect on depression remained significant after controlling for improvement in motor symptoms (mean [SE] difference, -0.23 [0.09], P = .009). There were no serious adverse events in the combined rasagiline-antidepressant group suggestive of serotonin syndrome. CONCLUSIONS AND RELEVANCE: The combination of rasagiline and antidepressants in patients with de novo PD is associated with reduced worsening of a range of NMSs in preliminary analyses. Adverse effects appear uncommon with this combination. These findings suggest a role for dopamine-enhancing therapies in NMSs in early PD and encourage further study and confirmation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00256204.

Sex differences in Parkinson's disease and other movement disorders.

Movement disorders including Parkinson's disease (PD), Huntington's disease (HD), chorea, tics, and Tourette's syndrome (TS) display sex differences in disease susceptibility, disease pathogenesis, and clinical presentation. PD is more common in males than in females. Epidemiologic studies suggest that exposure to endogenous and exogenous estrogen contributes to these sex differences. There is extensive evidence that estrogen prevents dopaminergic neuron depletion induced by neurotoxins in PD animal models and therefore is neuroprotective. Estrogen may also decrease the efficacy of other neuroprotective substances such as caffeine in females but not males. Sex chromosomes can exert effects independent of sex steroid hormones on the development and maintenance of the dopamine system. As a result of hormone, chromosome and other unknown effects, there are sexual dimorphisms in the basal ganglia, and at the molecular levels in dopaminergic neurons that may lead to distinct mechanisms of pathogenesis in males and females. In this review, we summarize the evidence that estrogen and selective estrogen receptor modulators are neuroprotective in PD and discuss potential mechanisms of action. We also briefly review how sex differences in basal ganglia function and dopaminergic pathways may impact HD, chorea, and tics/Tourette's syndrome. Further understanding of these sex differences may lead to novel therapeutic strategies for prevention and treatment of these diseases.

Phonemic verbal fluency decline after subthalamic nucleus deep brain stimulation does not depend on number of microelectrode recordings or lead tip placement.

BACKGROUND: Evidence suggests that both motor improvement and decline in verbal fluency in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) may be attributed to a lead implantation effect. OBJECTIVE: We investigated whether the number of microelectrode recording (MER) passes influenced either motor UPDRS scores just prior to stimulation initiation at 4 weeks or decline in verbal fluency 6-24 months after surgery. METHODS: We retrospectively analyzed 50 PD patients who underwent bilateral STN DBS. Off medication UPDRS III motor scores were obtained before surgery and before stimulation was initiated. Neuropsychological testing was completed pre- and post-operatively in 28 patients at a mean of 377 days. Coordinates of lead tip and active stimulation site were calculated. RESULTS: There was no improvement in off-medication UPDRS III motor scores at a mean 33.9 days following surgery, with mean change of 0.04 ± 10.48 (p = 0.98). There was no correlation between the number of MER passes and change in individual UPDRS motor score (r = -0.0001, p = 1.0). We observed significant decline in phonemic verbal fluency by 16% (p = 0.003) but it was not correlated with number of left hemisphere (r = -0.15, p = 0.46), or total number of passes (r = -0.02, p = 0.94) or coordinates of the lead tip or active stimulation site. There was a trend toward correlation with age (r = 0.38, p = 0.07). CONCLUSIONS: Significant decline in phonemic verbal fluency did not correlate with surgical passes nor with location of the lead tip or active stimulation site. These data suggest that age may influence verbal fluency decline more than surgical technique.