Journal of Parkinson's Disease - Volume 11, issue 4

Authors: Wong, Joshua K. | Hilliard, Justin D. | Holanda, Vanessa M. | Gunduz, Aysegul | Wagle Shukla, Aparna | Foote, Kelly D. | Okun, Michael S.

Article Type: Short Communication

Abstract: Deep brain stimulation (DBS) is an effective neuromodulatory therapy for Parkinson’s disease (PD). Early studies using globus pallidus internus (GPi) DBS for PD profiled the nucleus as having two functional zones. This concept disseminated throughout the neuromodulation community as the “GPi triangle”. Although our understanding of the pallidum has greatly evolved over the past 20 years, we continue to reference the triangle in our clinical decision-making process. We propose a new direction, termed the spatial boundary hypothesis, to build upon the 2-dimensional outlook on GPi DBS. We believe an updated 3-D GPi model can produce more consistent, positive patient outcomes.

Keywords: Deep brain stimulation, DBS, globus pallidus, GPi, Parkinson’s disease, targeting, neuromodulation

DOI: 10.3233/JPD-212820

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1881-1885, 2021

Authors: Wenzel, Gregor R. | Roediger, Jan | Brücke, Christof | Marcelino, Ana Luísa de A. | Gülke, Eileen | Pötter-Nerger, Monika | Scholtes, Heleen | Wynants, Kenny | Juárez Paz, León M. | Kühn, Andrea A.

Article Type: Research Article

Abstract: Background: Recent technological advances in deep brain stimulation (DBS) (e.g., directional leads, multiple independent current sources) lead to increasing DBS-optimization burden. Techniques to streamline and facilitate programming could leverage these innovations. Objective: We evaluated clinical effectiveness of algorithm-guided DBS-programming based on wearable-sensor-feedback compared to standard-of-care DBS-settings in a prospective, randomized, crossover, double-blind study in two German DBS centers. Methods: For 23 Parkinson’s disease patients with clinically effective DBS, new algorithm-guided DBS-settings were determined and compared to previously established standard-of-care DBS-settings using UPDRS-III and motion-sensor-assessment. Clinical and imaging data with lead-localizations were analyzed to evaluate characteristics of …algorithm-derived programming compared to standard-of-care. Six different versions of the algorithm were evaluated during the study and 10 subjects programmed with uniform algorithm-version were analyzed as a subgroup. Results: Algorithm-guided and standard-of-care DBS-settings effectively reduced motor symptoms compared to off-stimulation-state. UPDRS-III scores were reduced significantly more with standard-of-care settings as compared to algorithm-guided programming with heterogenous algorithm versions in the entire cohort. A subgroup with the latest algorithm version showed no significant differences in UPDRS-III achieved by the two programming-methods. Comparing active contacts in standard-of-care and algorithm-guided DBS-settings, contacts in the latter had larger location variability and were farther away from a literature-based optimal stimulation target. Conclusion: Algorithm-guided programming may be a reasonable approach to replace monopolar review, enable less trained health-professionals to achieve satisfactory DBS-programming results, or potentially reduce time needed for programming. Larger studies and further improvements of algorithm-guided programming are needed to confirm these results. Show more

Keywords: Deep brain stimulation, Parkinson’s disease, algorithm, wearable device feedback, double-blind, subthalamic nucleus

DOI: 10.3233/JPD-202480

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1887-1899, 2021

Authors: Simonet, Cristina | Galmes, Miquel A. | Lambert, Christian | Rees, Richard N. | Haque, Tahrina | Bestwick, Jonathan P. | Lees, Andrew J. | Schrag, Anette | Noyce, Alastair J.

Article Type: Research Article

Abstract: Background: Bradykinesia is the defining motor feature of Parkinson’s disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. Objective: To develop a quantitative method to track repetitive tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia. Methods: This was a cross-sectional study of 99 participants (early-stage PD = 26, controls = 64, idiopathic anosmia = 9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per …second. From each video, amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second) was extracted. Clinical assessment was based on the motor section of the MDS-UPDRS. Results: People in the early stage of PD performed the task with slower velocity (p  < 0.001) and with greater frequency slope than controls (p  = 0.003). The combination of reduced velocity and greater frequency slope obtained the best accuracy to separate early-stage PD from controls based on metric thresholds alone (AUC = 0.88). Individuals with anosmia exhibited slower velocity (p  = 0.001) and smaller amplitude (p  < 0.001) compared with controls. Conclusion: We present a simple, proof-of-concept method to detect early motor dysfunction in PD. Mean tap velocity appeared to be the best parameter to differentiate patients with PD from controls. Patients with anosmia also showed detectable differences in motor performance compared with controls which may suggest that some were in the prodromal phase of PD. Show more

Keywords: Anosmia, bradykinesia, Parkinson’s disease, tapping test, technology

DOI: 10.3233/JPD-212683

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1901-1915, 2021

Authors: Turner, Travis H. | Atkins, Alexandra | Keefe, Richard S.E.

Article Type: Research Article

Abstract: Background: Cognitive impairment is common in Parkinson’s disease (PD) and highly associated with loss of independence, caregiver burden, and assisted living placement. The need for cognitive functional capacity tools validated for use in PD clinical and research applications has thus been emphasized in the literature. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT-SL) is a tablet-based instrument that assesses proficiency for performing real world tasks in a highly realistic environment. Objective: The present study explored application of the VRFCAT-SL in clinical assessments of patients with PD. Specifically, we examined associations between VRFCAT-SL performance and measures of cognition, motor …severity, and self-reported cognitive functioning. Methods: The VRFCAT-SL was completed by a sample of 29 PD patients seen in clinic for a comprehensive neuropsychological evaluation. Fifteen patients met Movement Disorders Society Task Force criteria for mild cognitive impairment (PD-MCI); no patients were diagnosed with dementia. Non-parametric correlations between VRFCAT-SL performance and standardized neuropsychological tests and clinical measures were examined. Results: VRFCAT-SL performance was moderately associated with global rank on neuropsychological testing and discriminated PD-MCI. Follow-up analyses found completion time was associated with visual memory, sustained attention, and set-switching, while errors were associated with psychomotor inhibition. No clinical or motor measures were associated with VRFCAT-SL performance. Self-report was not associated with VRFCAT-SL or neuropsychological test performance. Conclusion: The VRFCAT-SL appears to provide a useful measure of cognitive functional capacity that is not confounded by PD motor symptoms. Future studies will examine utility in PD dementia. Show more

Keywords: Assessment, cognitive capacity, functional capacity, functional outcome, mild cognitive impairment, neuropsychology, Parkinson’s disease, virtual reality

DOI: 10.3233/JPD-212688

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1917-1925, 2021

Authors: Riggare, Sara | Hägglund, Maria | Bredenoord, Annelien L. | de Groot, Martijn | Bloem, Bastiaan R.

Article Type: Article Commentary

Abstract: Using Parkinson’s disease as an exemplary chronic condition, this Commentary discusses ethical aspects of using self-tracking for personal science, as compared to using self-tracking in the context of conducting clinical research on groups of study participants. Conventional group-based clinical research aims to find generalisable answers to clinical or public health questions. The aim of personal science is different: to find meaningful answers that matter first and foremost to an individual with a particular health challenge. In the case of personal science, the researcher and the participant are one and the same, which means that specific ethical issues may arise, such …as the need to protect the participant against self-harm. To allow patient-led research in the form of personal science in the Parkinson field to evolve further, the development of a specific ethical framework for self-tracking for personal science is needed. Show more

Keywords: Parkinson’s disease, self-tracking, ethics, remote monitoring, selfcare, patient empowerment

DOI: 10.3233/JPD-212647

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1927-1933, 2021

Authors: Fearn, Sarah | Bartolomeu Pires, Sandra | Agarwal, Veena | Roberts, Helen C. | Spreadbury, John | Kipps, Christopher

Article Type: Research Article

Abstract: Background: The reasons for acute hospital admissions among people with Parkinson’s disease are well documented. However, understanding of crises that are managed in the community is comparatively lacking. Most existing literature on the causes of crisis for people with Parkinson’s disease (PwP) uses hospital data and excludes the individual’s own perspective on the crisis trigger and the impact of the crisis on their care needs. Objective: To identify the causes and impact of crises in both community and hospital settings, from a patient and carer perspective. Methods: A total of 550 UK-based PwP and carers completed …a survey on (a) their own personal experiences of crisis, and (b) their general awareness of potential crisis triggers for PwP. Results: In addition to well-recognised causes of crisis such as falls, events less widely associated with crisis were identified, including difficulties with activities of daily living and carer absence. The less-recognised crisis triggers tended to be managed more frequently in the community. Many of these community-based crises had a greater impact on care needs than the better-known causes of crisis that more frequently required hospital care. PwP and carer responses indicated a good general knowledge of potential crisis triggers. PwP were more aware of mental health issues and carers were more aware of cognitive impairment and issues with medications. Conclusion: These findings could improve care of Parkinson’s by increasing understanding of crisis events from the patient and carer perspective, identifying under-recognised crisis triggers, and informing strategies for best recording symptoms from PwP and carers. Show more

Keywords: Parkinson’s disease, hospital admissions, care needs, crisis, patient perspective, resource use, activities of daily living, caregivers, surveys and questionnaires, content analysis

DOI: 10.3233/JPD-212641

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1935-1945, 2021

Authors: Jeong, Seong Ho | Yoo, Han Soo | Chung, Seok Jong | Jung, Jin Ho | Lee, Yang Hyun | Baik, Kyoungwon | Sohn, Young H. | Lee, Phil Hyu

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms (NPS) are the most common non-motor symptom in Parkinson’s disease (PD). Objective: To investigate the association between the burden of NPS and motor prognosis in patients with PD. Methods: We enrolled 329 drug-naïve patients with PD, who was non-demented and followed-up≥2 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging and neuropsychiatric inventory (NPI) scores. We performed a survival analysis and a linear mixed model analysis to assess longitudinal motor outcomes according to the NPI total score. Results: The Kaplan-Meier analysis showed no difference in the …development of levodopa-induced dyskinesia and wearing-off according to the NPI total score. However, higher burden of NPI total score was associated with earlier freezing of gait (FOG) development in the time-dependent Cox regression models after adjusting for age at symptom onset, sex, disease duration, Unified PD Rating Scale motor score, baseline Mini-Mental State Examination score, DAT activity in the posterior putamen and levodopa-equivalent daily dose (LEDD) (Hazard ratio 1.047, p  = 0.002). A linear mixed model analysis revealed that patients with a higher NPI total score had a more rapid LEDD increment (NPI×time, p  = 0.003). Among 52 patients with PD who eventually developed FOG during the follow-up period, there was a significant correlation between the NPI total score and time with FOG development (γ = –0.472; p  = 0.001) after adjusting for confounding factors. Conclusion: The present study demonstrated that the severity of NPS is a predictor of early freezing and motor progression in patients with PD. Show more

Keywords: Parkinson’s disease, neuropsychiatric symptoms, motor prognosis

DOI: 10.3233/JPD-212660

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1947-1956, 2021

Authors: Javidnia, Monica | Arbatti, Lakshmi | Hosamath, Abhishek | Eberly, Shirley W. | Oakes, David | Shoulson, Ira

Article Type: Research Article

Abstract: Background: Postural instability is an intractable sign of Parkinson’s disease, associated with poor disease prognosis, fall risk, and decreased quality of life. Objective: 1) Characterize verbatim reports of postural instability and associated symptoms (gait disorder, balance, falling, freezing, and posture), 2) compare reports with responses to three pre-specified questions from Part II of the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), and 3) examine postural instability symptoms and MDS-UPDRS responses as predictors of future falls. Methods: Fox Insight research participants reported their problems attributed to PD in their own words using the Parkinson Disease …Patient Reports of Problems (PD-PROP). Natural language processing, clinical curation, and data mining techniques were applied to classify text into problem domains and clinically-curated symptoms. Baseline postural instability symptoms were mapped to MDS-UPDRS questions 2.11–2.13. T -tests and chi-square tests were used to compare postural instability reporters and non-reporters, and Cochran-Armitage trend tests were used to evaluate associations between PD-PROP and MDS-UPDRS responses; survival methods were utilized to evaluate the predictive utility of PD-PROP and MDS-UPDRS responses in time-to-fall analyses. Results: Of participants within 10 years of PD diagnosis, 9,692 (56.0%) reported postural instability symptoms referable to gait unsteadiness, balance, falling, freezing, or posture at baseline. Postural instability symptoms were significantly associated with patient-reported measures from the MDS-UPDRS questions. Balance problems reported on PD-PROP and MDS-UPDRS 2.11–2.13 measures were predictive of future falls. Conclusion: Verbatim-reported problems captured by the PD-PROP and categorized by natural language processing and clinical curation and MDS-UPDRS responses predicted falls. The PD-PROP output was more granular than, and as informative as, the categorical responses. Show more

Keywords: Clinical trials, disease progression, falling, observational research, patient-reported outcomes

DOI: 10.3233/JPD-212636

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1957-1964, 2021

Authors: Di Luca, Daniel G. | McArthur, Eric W. | Willis, Allison | Martino, Rosemary | Marras, Connie

Article Type: Research Article

Abstract: Background: Dysphagia is a frequent complication that may increase morbidity and mortality in Parkinson’s disease (PD). Nevertheless, there is limited data on its objective impact on healthcare outcomes. Objective: To investigate the outcomes associated with dysphagia in hospitalized patients with PD and associated healthcare costs and utilization. Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) data from 2004 to 2014. A multivariable regression analysis was adjusted for demographic, and comorbidity variables to examine the association between dysphagia and associated outcomes. Logistic and negative binomial regressions were used to estimate odds or …incidence rate ratios for binary and continuous outcomes, respectively. Results: We identified 334,395 non-elective hospitalizations of individuals with PD, being 21,288 (6.36%) associated with dysphagia. Patients with dysphagia had significantly higher odds of negative outcomes, including aspiration pneumonia (AOR 7.55, 95%CI 7.29–7.82), sepsis (AOR 1.91, 95%CI 1.82–2.01), and mechanical ventilation (AOR 2.00, 95%CI 1.86–2.15). For hospitalizations with a dysphagia code, the length of stay was 44%(95%CI 1.43–1.45) longer and inpatient costs 46%higher (95%CI 1.44–1.47) compared to those without dysphagia. Mortality was also substantially increased in individuals with PD and dysphagia (AOR 1.37, 95%CI 1.29–1.46). Conclusion: In hospitalized patients with PD, dysphagia was a strong predictor of adverse clinical outcomes, and associated with substantially prolonged length of stay, higher mortality, and care costs. These results highlight the need for interventions focused on early recognition and prevention of dysphagia to avoid complications and lower costs in PD patients. Show more

Keywords: Dysphagia, Parkinson’s disease, neurodegenerative diseases, healthcare costs

DOI: 10.3233/JPD-212798

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1965-1971, 2021

Authors: Radojević, Branislava | Dragašević-Mišković, Nataša T. | Marjanović, Ana | Branković, Marija | Dobričić, Valerija | Milovanović, Andona | Tomić, Aleksandra | Svetel, Marina | Petrović, Igor | Jančić, Ivan | Stanisavljević, Dejana | Savić, Miroslav M. | Kostić, Vladimir S.

Article Type: Research Article

Abstract: Background: Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson’s disease (PDP). Objective: We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. Methods: PD patients (n  = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT , rs6277, rs1076560, and rs2283265 in DRD2 , and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in …the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. Results: Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson’s Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. Conclusion: Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies. Show more

Keywords: COMT Val158Met , DAT1 SLC6A3 , DRD2 , genetic polymorphisms, hallucinations, Parkinson’s disease, psychosis

DOI: 10.3233/JPD-212716

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1973-1980, 2021

Authors: Heilbron, Karl | Jensen, Melanie P. | Bandres-Ciga, Sara | Fontanillas, Pierre | Blauwendraat, Cornelis | Nalls, Mike A. | Singleton, Andrew B. | Smith, George Davey | Cannon, Paul | Noyce, Alastair J. | The 23andMe Research Team

Article Type: Research Article

Abstract: Background: Tobacco smoking and alcohol intake have been identified in observational studies as potentially protective factors against developing Parkinson’s disease (PD); the impact of body mass index (BMI) on PD risk is debated. Whether such epidemiological associations are causal remains unclear. Mendelian randomsation (MR) uses genetic variants to explore the effects of exposures on outcomes; potentially reducing bias from residual confounding and reverse causation. Objective: Using MR, we examined relationships between PD risk and three unhealthy behaviours: tobacco smoking, alcohol intake, and higher BMI. Methods: 19,924 PD cases and 2,413,087 controls were included in the analysis. …We performed genome-wide association studies to identify single nucleotide polymorphisms associated with tobacco smoking, alcohol intake, and BMI. MR analysis of the relationship between each exposure and PD was undertaken using a split-sample design. Results: Ever-smoking reduced the risk of PD (OR 0.955; 95%confidence interval [CI] 0.921–0.991; p  = 0.013). Higher daily alcohol intake increased the risk of PD (OR 1.125, 95%CI 1.025–1.235; p  = 0.013) and a 1 kg/m2 higher BMI reduced the risk of PD (OR 0.988, 95%CI 0.979–0.997; p  = 0.008). Sensitivity analyses did not suggest bias from horizontal pleiotropy or invalid instruments. Conclusion: Using split-sample MR in over 2.4 million participants, we observed a protective effect of smoking on risk of PD. In contrast to observational data, alcohol consumption appeared to increase the risk of PD. Higher BMI had a protective effect on PD, but the effect was small. Show more

Keywords: Parkinson’s disease, 23andMe, smoking, alcohol, BMI

DOI: 10.3233/JPD-202487

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1981-1993, 2021

Authors: Snyder, Allison | Gruber-Baldini, Ann L. | Rainer von Coelln, F. | Savitt, Joseph M. | Reich, Stephen G. | Armstrong, Melissa J. | Shulman, Lisa M.

Article Type: Research Article

Abstract: Background: Cognitive impairment (CI) is common in Parkinson’s disease (PD) and an important cause of disability. Screening facilitates early detection of CI and has implications for management. Preclinical disability is when patients have functional limitations but maintain independence through compensatory measures. Objective: The objective of this study was to investigate the relationship between scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) with levels of PD severity and disability. Methods: PD patients (n  = 2,234) in a large observational study were stratified by disease severity, based on Total Unified Parkinson’s Disease Rating Scale (Total …UPDRS) and Hoehn and Yahr (HY) stage. Using MMSE (n  = 1,184) or MoCA (n  = 1,050) and basic (ADL) and instrumental activities of daily living (IADL) scales for disability, linear regression analysis examined associations between cognitive status and disability. Results: Cognition and disability were highly correlated, with the strongest correlation between IADL and MoCA. Only 16.0% of mean MMSE scores were below threshold for CI (28) and only in advanced PD (Total UPDRS 60+, HY≥3). MoCA scores fell below CI threshold (26) in 66.2% of the sample and earlier in disease (Total UPDRS 30+, HY≥2), corresponding with impairments in ADLs. Conclusion: In a large clinical dataset, a small fraction of MMSE scores fell below cutoff for CI, reinforcing that MMSE is an insensitive screening tool in PD. MoCA scores indicated CI earlier in disease and coincided with disability. This study shows that MoCA, but not MMSE is sensitive to the emergence of early cognitive impairment in PD and correlates with the concomitant onset of disability. Show more

Keywords: Parkinson’s disease, cognitive impairment, cognitive screening, disability

DOI: 10.3233/JPD-212705

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1995-2003, 2021

Authors: Hamada, Tomoya | Higashiyama, Yuichi | Saito, Asami | Morihara, Keisuke | Landin-Romero, Ramon | Okamoto, Mitsuo | Kimura, Katsuo | Miyaji, Yousuke | Joki, Hideto | Kishida, Hitaru | Doi, Hiroshi | Ueda, Naohisa | Takeuchi, Hideyuki | Tanaka, Fumiaki

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) in Parkinson’s disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown. Objective: This study aimed to investigate the relative diagnostic accuracy of qualitative (clustering and switching) verbal fluency strategies and their correlates with functional imaging in PD-MCI. Methods: Forty-five patients with PD (26 with MCI and 19 without MCI) and 25 …healthy controls underwent comprehensive neurocognitive testing and resting-state functional magnetic resonance imaging. MCI in patients with PD was diagnosed according to established clinical criteria. The diagnostic accuracy of verbal fluency measures was determined via receiver operating characteristic analysis. Changes in brain functional connectivity between groups and across clinical measures were assessed using seed-to-voxel analyses. Results: Patients with PD-MCI generated fewer words and switched less frequently in semantic and phonemic fluency tasks compared to other groups. Switching in semantic fluency showed high diagnostic accuracy for PD-MCI and was associated with reduced functional connectivity in the salience network. Conclusion: Our results indicate that reduced switching in semantic fluency tasks is a sensitive and specific marker for PD-MCI. Qualitative verbal fluency deficits and salience network dysfunction represent early clinical changes observed in PD-MCI. Show more

Keywords: Brain connectivity, mild cognitive impairment, Parkinson’s disease, salience network, verbal fluency

DOI: 10.3233/JPD-202473

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2005-2016, 2021

Authors: Loftus, Andrea M. | Nielsen, Chloe | Corti, Emily J. | Starkstein, Sergio | Gasson, Natalie | Egan, Sarah J.

Article Type: Research Article

Abstract: Background: Recent research suggests that a significant number of those who receive advanced treatments for Parkinson’s disease (PD) do not report improvements for some symptoms, which may relate to their pre-treatment expectations. It is important that expectations of treatment are measured and discussed prior to advanced treatment. Objective: The primary aim of this study was to develop a measure of treatment expectations of two advanced-stage treatments in PD, deep brain stimulation (DBS), and Levodopa/Carbidopa Intestinal Gel (LCIG). A secondary aim was to explore potential predictors of treatment expectations. Methods: The questionnaire-based measure was developed by researchers …in conjunction with a highly experienced clinician, and evaluated treatment expectations in 189 people aged 46–91 years (M  = 71.35, SD  = 8.73; 61% male) with idiopathic PD. Results: The overall measure demonstrated excellent internal consistency (α = 0.96). Exploratory factor analysis suggested the scale was unidimensional for both DBS and LCIG. Participant expectations of the two treatments differed significantly, with expectations being higher for DBS. Perceived symptom severity was the strongest predictor of treatment expectations. Conclusion: This scale has potential to inform clinicians about client expectations prior to advanced stage therapy for PD, with a view to the management of these expectations. Further evaluation of the scale is required across different treatment contexts. Show more

Keywords: Parkinson’s disease, treatment expectations, deep brain stimulation, Levodopa/carbidopa intestinal gel, quality of life, psychological

DOI: 10.3233/JPD-212777

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2017-2026, 2021

Authors: Silbergleit, Alice K. | Schultz, Lonni | Hamilton, Kendra | LeWitt, Peter A. | Sidiropoulos, Christos

Article Type: Research Article

Abstract: Background: Hypokinetic dysarthria and dysphagia are known features of Parkinson’s disease; however, self-perception of their handicapping effects on emotional, physical, and functional aspects of quality of life over disease duration is less understood. Objective: 1) Based upon patient self-perception, to determine the relationship of the handicapping effects of dysphagia and dysphonia with time since diagnosis in individuals with Parkinson’s disease; 2)To determine if there is a relationship between voice and swallowing handicap throughout the course of Parkinson’s disease. Method: 277 subjects completed the Dysphagia Handicap Index and the Voice Handicap Index. Subjects were divided into three …groups based on disease duration: 0–4 years, 5–9 years, and 10 + years. Results: Subjects in the longer duration group identified significantly greater perceptions of voice and swallowing handicap compared to the shorter duration groups. There was a significant positive correlation between the DHI and VHI. Conclusion: Self-perception of swallowing and voice handicap in Parkinson’s disease are associated with later stages of disease and progress in a linear fashion. Self-perception of voice and swallowing handicap parallel each other throughout disease progression in Parkinson’s disease. Individuals may be able to compensate for changes in voice and swallowing early while sensory perceptual feedback is intact. Results support early targeted questioning of patient self-perception of voice and swallowing handicap as identification of one problem indicates awareness of the other, thus creating an opportunity for early treatment and maintenance of swallowing and communication quality of life for as long as possible. Show more

Keywords: Disease duration, dysarthria, dysphagia, handicapping effects, self-perception

DOI: 10.3233/JPD-212621

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2027-2034, 2021

Authors: Utz, Kathrin S. | Martini, Max | Mrochen, Anne | Lambrecht, Vera | Süß, Patrick | Renner, Bertold | Freiherr, Jessica | Schenk, Thomas | Winkler, Jürgen | Marxreiter, Franz

Article Type: Research Article

Abstract: Background: There is growing interest in non-motor symptoms in Parkinson’s disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. Objective: We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a …multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. Methods: Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. Results: In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. Conclusion: We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD. Show more

Keywords: Parkinson’s disease, anhedonia, hyposmia, non-motor symptoms, depression, apathy, Sniffin’ Sticks, affective pictures

DOI: 10.3233/JPD-212812

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2035-2045, 2021

Authors: Luque-Casado, Antonio | Novo-Ponte, Sabela | Sánchez-Molina, José Andrés | Sevilla-Sánchez, Marta | Santos-García, Diego | Fernández-del-Olmo, Miguel

Article Type: Research Article

Abstract: Background: Despite the frequent use of the Timed Up and Go (TUG) test in clinical trials, evaluation of longitudinal test-retest reliability is generally lacking and still inconclusive for patients with Parkinson’s disease (PD). Objective: We aimed to further investigate long-term reliability and sensitivity of the TUG test among this population. Furthermore, we explored alternative assessment strategies of the test aimed at elucidating whether the inclusion or combination of timed trials may have potential implications on outcome measure. Methods: Relative and absolute reliability of the TUG performance were obtained in forty-three subjects with PD over three timed …trials in two different testing sessions separated by a two-months period. Results: Our results reported excellent intra-session and moderate inter-session reliability coefficients. The use of different assessment strategies of the TUG was found to have an important impact on outcome measure, highlighting the averaging of several timed trials in each testing session as a recommended alternative to minimize measurement error and increase reliability in longitudinal assessments. Nevertheless, beyond acceptable reliability, poor trial-to-trial stability of the measure appears to exist, since the ranges of expected variability upon retesting were wide and the incidence of spurious statistical effects was not negligible, especially in longitudinal repeated testing. Conclusion: Limitations may exist in the interpretation of the TUG outputs as part of longitudinal assessments aimed at evaluating treatment effectiveness in PD population. Researchers and practitioners should be aware of these concerns to prevent possible misrepresentations of functional ability in patients for a particular intervention. Show more

Keywords: Absolute reliability, intervention, learning effects, long-term, measurement error, minimal detectable change, relative reliability

DOI: 10.3233/JPD-212687

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2047-2055, 2021

Authors: Albrecht, Franziska | Pereira, Joana B. | Mijalkov, Mite | Freidle, Malin | Johansson, Hanna | Ekman, Urban | Westman, Eric | Franzén, Erika

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week …period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects. Show more

Keywords: Randomized controlled trial, magnetic resonance imaging, idiopathic Parkinson’s disease, gait, physical exercise, putamen, gray matter

DOI: 10.3233/JPD-212801

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2057-2071, 2021

Authors: Padmanabhan, Purnima | Sreekanth Rao, Keerthana | Gonzalez, Anthony J. | Pantelyat, Alexander Y. | Chib, Vikram S. | Roemmich, Ryan T.

Article Type: Research Article

Abstract: Background: Gait slowing is a common feature of Parkinson’s disease (PD). Many therapies aim to improve gait speed in persons with PD, but goals are often imprecise. How fast should each patient walk? And how do persons with PD benefit from walking faster? There is an important need to understand how walking speed affects fundamental aspects of gait—including energy cost and stability—that could guide individualized therapy decisions in persons with PD. Objective: We investigated how changes in walking speed affected energy cost and spatiotemporal gait parameters in persons with PD. We compared these effects between dopaminergic medication states …and to those observed in age-matched control participants. Methods: Twelve persons with PD and twelve control participants performed treadmill walking trials spanning at least five different speeds (seven speeds were desired, but not all participants could walk at the fastest speeds). Persons with PD participated in two walking sessions on separate days (once while optimally medicated, once after 12-hour withdrawal from dopaminergic medication). We measured kinematic and metabolic data across all trials. Results: Persons with PD significantly reduced energy cost by walking faster than their preferred speeds. This held true across medication conditions and was not observed in control participants. The patient-specific walking speeds that reduced energy cost did not significantly affect gait variability metrics (used as proxies for gait stability). Conclusion: The gait slowing that occurs with PD results in energetically suboptimal walking. Rehabilitation strategies that target patient-specific increases in walking speed could result in a less effortful gait. Show more

Keywords: Gait, Parkinson’s disease, rehabilitation, energy, dopamine

DOI: 10.3233/JPD-212613

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2073-2084, 2021

Authors: Kumar, Srishti | Shen, Julia W. | Grimes, David | Mestre, Tiago | Thavorn, Kednapa

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a complex and debilitating condition that requires care from a multispecialty team. The Integrated Parkinson Care Network (IPCN) is an innovative pragmatic care model that focuses on integrated care, self-management support and technology-enabled care. Objective: This study aims to estimate the costs of the IPCN and assess whether benefits gained from the intervention offset its costs based on a single center experience. Methods: We conducted a return on investment (ROI) analysis of the IPCN from a societal perspective. The ROI for the IPCN was estimated as a ratio …of the net savings and the intervention cost. The intervention cost was calculated as a sum of set-up and implementation costs. Cost savings was measured as the absolute reduction in the societal costs realized by PD patients. A positive ROI indicated that savings generated from the intervention offset its cost. Results: The total cost of the IPCN for 100 PD patients was C$135,669, or C$226 per patient per month. IPCN was associated with the reduction in societal cost of C$915 per patient per month (95%CI: –2,782, 951). The ROI per PD patient per month for the IPCN was 3.08 (95%CI: –0.60, 22.93), suggesting that for every C$1 invested in the IPCN, C$4.08 is gained through reduction in societal costs. The returns were greater among advanced PD patients. Conclusion: The IPCN has the potential to offer a good return on investment for PD patients, and its value for money is higher among advanced PD patients. Show more

Keywords: Economic evaluation, Parkinson’s disease, integrated care, self-management support, technology-enabled care

DOI: 10.3233/JPD-212578

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2085-2091, 2021

Authors: Nonnekes, Jorik | Koehler, Peter | Bloem, Bastiaan R.

Article Type: Article Commentary

DOI: 10.3233/JPD-212933

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2093-2094, 2021