Total Unified Parkinson's Disease Research Articles

Long-Term Follow-Up of the LEAP Study: Early Versus Delayed Levodopa in Early Parkinson's Disease.

The Levodopa in EArly Parkinson's disease study showed no effect of earlier versus later levodopa initiation on Parkinson's disease (PD) progression over 80 weeks. We now report the effects over 5 years. The Levodopa in EArly Parkinson's disease study randomly assigned patients to levodopa/carbidopa 300/75 mg daily for 80 weeks (early start) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed start). Follow-up visits were performed 3 and 5 years after baseline. We assessed the between-group differences in terms of square root transformed total Unified Parkinson's Disease Rating Scale score at 3 and 5 years with linear regression. We compared the prevalence of dyskinesia, prevalence of wearing off, and the levodopa equivalent daily dose. A total of 321 patients completed the 5-year visit. The adjusted square root transformed total Unified Parkinson's Disease Rating Scale did not differ between treatment groups at 3 (estimated difference, 0.17; standard error, 0.13; P = 0.18) and 5 years (estimated difference, 0.24; standard error, 0.13; P = 0.07). At 5 years, 46 of 160 patients in the early-start group and 62 of 161 patients in the delayed-start group experienced dyskinesia (P = 0.06). The prevalence of wearing off and the levodopa equivalent daily dose were not significantly different between groups. We did not find a difference in disease progression or in prevalence of motor complications between patients with early PD starting treatment with a low dose of levodopa 40 weeks earlier versus 40 weeks later over the subsequent 5 years. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Feasibility of regional center telehealth visits utilizing a rural research network in people with Parkinson's disease.

Impaired motor and cognitive function can make travel cumbersome for People with Parkinson's disease (PwPD). Over 50% of PwPD cared for at the University of Arkansas for Medical Sciences (UAMS) Movement Disorders Clinic reside over 30 miles from Little Rock. Improving access to clinical care for PwPD is needed. To explore the feasibility of remote clinic-to-clinic telehealth research visits for evaluation of multi-modal function in PwPD. PwPD residing within 30 miles of a UAMS Regional health center were enrolled and clinic-to-clinic telehealth visits were performed. Motor and non-motor disease assessments were administered and quantified. Results were compared to participants who performed at-home telehealth visits using the same protocols during the height of the COVID pandemic. Compared to the at-home telehealth visit group (n = 50), the participants from regional centers (n = 13) had similar age and disease duration, but greater disease severity with higher total Unified Parkinson's disease rating scale scores (Z = -2.218, p = 0.027) and lower Montreal Cognitive Assessment scores (Z = -3.350, p < 0.001). Regional center participants had lower incomes (Pearson's chi = 21.3, p < 0.001), higher costs to attend visits (Pearson's chi = 16.1, p = 0.003), and lived in more socioeconomically disadvantaged neighborhoods (Z = -3.120, p = 0.002). Prior research participation was lower in the regional center group (Pearson's chi = 4.5, p = 0.034) but both groups indicated interest in future research participation. Regional center research visits in PwPD in medically underserved areas are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

A fixel-based analysis of white matter reductions early detects Parkinson disease with mild cognitive impairment

BackgroundWhite matter (WM) tract alterations are early signs of cognitive impairment in Parkinson disease (PD) patients. Fixel-based analysis (FBA) has advantages over traditional diffusion tensor imaging in managing complex and crossing fibers. We used FBA to measure fiber-specific changes in patients with PD mild cognitive impairment (PD-MCI) and PD normal cognition (PD-NC). MethodsSeventy-one patients with PD without dementia were included: 39 PD-MCI and 32 PD-NC. All underwent diffusion-weighted imaging, clinical examinations, and tests to evaluate their cognitive function globally and in five cognitive domains. FBA was used to investigate fiber-tract alterations and compare PD-MCI with PD-NC subjects. Correlations with each cognitive test were analyzed. ResultsPatients with PD-MCI were significantly older (P = 0.044), had a higher male-to-female ratio (P = 0.006) and total Unified Parkinson's Disease Rating Scale score (P = 0.001). All fixel-based metrics were significantly reduced within the body of the corpus callosum and superior corona radiata in PD-MCI patients (family-wise error-corrected P value < 0.05) compared with PD-NC patients. The cingulum, superior longitudinal fasciculi, and thalamocortical circuit exhibited predominantly fiber-bundle cross-section (FC) changes. In regression analysis, reduced FC values in cerebellar circuits were associated with poor motor function in PD-MCI patients and poor picture-naming ability in PD-NC patients. ConclusionsPD-MCI patients have significant WM alterations compared with PD-NC patients. FBA revealed these changes in various bundle tracts, helping us to better understand specific WM changes that are functionally implicated in PD cognitive decline. FBA is potentially useful in detecting early cognitive decline in PD.

Association between metabolic syndrome and progression in Parkinson's disease

BackgroundParkinson's disease (PD) and metabolic syndrome are separate entities that share common underlying pathophysiology. Management strategy for metabolic syndrome is clinically better characterized and finding a positive clinical correlation between the two could lead to a better understanding of Parkinson's disease progression and prognosis. PurposeTo explore the relationship between progression in PD and metabolic syndrome to characterize the underlying pathophysiology, which could then impact the clinical management of PD. MethodsUsing modified NCEP (National Cholesterol Education Program) ATP III (Adult Treatment Plan) criteria, patients enrolled in STEADY-PD III (Safety, Tolerability, and Efficacy Assessment of Isradipine) were classified into one of three categories of metabolic syndrome and compared on PD progression over a period of 3 years. ResultsParticipants with metabolic syndrome showed a trend for more progression in terms of PD, as measured by the total Unified Parkinson's Disease Rating Scale (UPDRS), the motor EDL (Experiences of daily living) scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and the Montreal Cognitive Assessment (MoCA). A significant trend for decline in MoCA was found in the group with metabolic syndrome (−0.78), compared with those without metabolic syndrome (0.14). Greater decline in MoCA signifies worse outcomes. ConclusionThe results demonstrate a trend in more clinical progression in PD in subjects with metabolic syndrome. However, results are limited by the sample size and the limited laboratory measurements available. We hope this study will encourage larger sample studies to explore this relationship further.

The effects of paroxetine therapy on depressive symptom and motor function in the treatment of depression with Parkinson's disease: A meta-analysis.

Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice. Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson's disease rating scale score, Hamilton anxiety rating scale score or adverse events. Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson's disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001). Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.

Predicting Parkinson's Disease Severity using Telemonitoring Data and Machine Learning Models: A Principal Component Analysis-based Approach for Remote Healthcare Services during COVID-19 Pandemic

Parkinson's disease (PD) is a progressive and chronic neurological condition that affects about 1% of the world's over-60 population. The COVID-19 pandemic has emphasized the significance of remote healthcare services, such as telemedicine, in managing chronic diseases such as PD. This research intends to construct machine learning (ML) models to predict PD severity utilizing vocal data derived from the UCI database for motor and total Unified Parkinson's disease rating scale (UPDRS) ratings. ML was used to study the association between voice vibration and PD, and PCA and ML models were utilized to minimize model complexity and compare the predictive performance of various statistical models for PD regression. The dataset included 5,875 medical voice records from 42 patients with early-stage PD who participated in a six-month clinical trial. The proposed PCA model simplified the model and achieved a root-mean-square error of 1.78 with an R-squared value of 0.95 for predicting the motor UPDRS and 1.78 with an R-squared value of 0.97 for predicting the total UPDRS. This work can give a framework for developing remote healthcare services for Parkinson's disease and other chronic conditions, which can be helpful during pandemics and other situations where access to in-person care is limited.

Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson's disease.

This study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson's disease (PD), so as to explore its application value in assessing the severity of Parkinson's disease. A total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson's Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated. The caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05). 11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.

Characteristics of fatigue in Parkinson's disease: A longitudinal cohort study.

To assess the prevalence, evolution, clinical characteristics, correlates and predictors of fatigue as well as to investigate the influence of comorbid fatigue on the longitudinal changes in motor and non-motor symptoms over a 2-year longitudinal follow-up period in a large cohort of patients with Parkinson's disease (PD). A total of 2,100 PD patients were enrolled from the Parkinson's Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC), and their motor and non-motor symptoms were assessed biennially using comprehensive scales, including the 16-item Parkinson Fatigue Scale (PFS-16). Each PD patient was categorized as PD with or without fatigue on the basis of a cut-off mean PFS-16 score of 3.3. The prevalence of fatigue in our cohort was 36.8%. Compared to PD patients without fatigue, PD patients with fatigue were more likely to be older, have a longer disease duration, and higher baseline levodopa equivalent daily dose (all p < 0.05). Moreover, PD patients with fatigue showed more severe motor and non-motor phenotypes than those without fatigue. Overall, high total Unified Parkinson's Disease Rating Scale (UPDRS) score (odds ratio [OR] = 1.016, 95% confidence interval [CI]: 1.009-1.024), Non-Motor Symptoms Scale score (OR = 1.022, 95% CI: 1.015-1.029), postural instability and gait difficulty (PIGD) subtype (OR = 1.586, 95% CI: 1.211-2.079), presence of excessive daytime sleepiness (EDS; OR = 1.343, 95% CI: 1.083-1.666), and wearing-off (OR = 1.282, 95% CI: 1.023-1.607) were significantly associated with fatigue in PD patients (all p < 0.05). High total UPDRS score at baseline (OR = 1.014, 95% CI: 1.002-1.027, p = 0.028) increased the risk of developing fatigue during follow-up. Although significant, the odds ratios were low and confidence intervals were narrow. Analysis of disease progression showed significant group differences in motor and non-motor symptoms. In comparison with the never-fatigue group, the persistent-fatigue group showed significantly greater progression in motor, autonomic dysfunction, sleep, depression and cognitive symptoms (all p < 0.05). Increased disease severity, presence of the PIGD subtype, EDS, and wearing-off were associated with fatigue in PD patients. Significant subgroup-level differences were observed in the progression of motor and non-motor symptoms across different fatigue subgroups of PD patients.

Somatoform Symptoms in Parkinson Disease.

Co-occurring somatoform symptoms complicate the diagnosis and treatment of Parkinson disease (PD). To learn more about the relationship between somatoform symptoms and PD by comparing demographic and clinical features across PD groups differing in somatoform symptom severity. Using standardized Brief Symptom Inventory-18 (BSI-18) scores to measure somatoform symptom severity, we assigned 1093 individuals with PD to one of four subgroups using comparisons to normative means: low (M < -½ SD), average (M ± ½ SD), high (M +½ SD to +1 SD), very high (M > +1 SD). We used demographics and disease severity measures to assess each subgroup. Most of the individuals with PD (56%) had high or very high somatoform symptom levels. Increased somatoform symptom levels were associated with female gender, lower socioeconomic status, greater disease duration, increased PD severity (Total Unified Parkinson's Disease Rating Scale), greater disability (Older Americans Resource and Services Disability subscale), increased BSI-18 Depression and Anxiety subscale scores, lower cognitive function (Mini-Mental State Examination), lower self-efficacy scores (Self-Efficacy to Manage Chronic Disease Scale), lower quality of life scores (SF-12 Health Status Survey), and greater medical comorbidity (Cumulative Illness Rating Scale-Geriatrics) (all comparisons: P < 0.001). We found no significant between-group differences for age, race, or marital status. Somatoform symptom severity in individuals with PD is associated with greater PD severity and disability and is more common in females and in individuals with low socioeconomic status. Greater awareness of somatoform symptoms should help improve PD treatment.

Association of serum uric acid and non-motor symptoms in Parkinson's disease: A cross-sectional study from a movement disorders clinic in Lagos, Nigeria

Background and Objective: The role of serum uric acid (SUA) as a biomarker in Parkinson's disease (PD) remains exploratory and has not been described in our population. The objective of this study was to explore the profile of SUA and its relationship to nonmotor symptoms (NMS) burden in PD. Methods: This cross-sectional study recruited 70 persons with PD and 140 matched healthy controls in Lagos, Nigeria. PD was diagnosed using the United Kingdom PD Society Brain Bank criteria. NMS were assessed with the NMS Questionnaire (NMS-Quest). SUA was measured using standard methods. Results: The mean ages of PD and controls were 63 ± 9.4 years and 62.9 ± 8.8 years, respectively (P = 0.65), with no difference when compared by sex. The median PD duration (interquartile range [IQR]) was 4 (4.25) years. Median Hoehn and Yahr stage (IQR) was 2.5 (1.0). The mean total unified Parkinson's disease rating scale score was 70.7 ± 23.7. The mean NMS-Quest score was 8.5 ± 3.8. Mean SUA level was significantly lower in PD compared to controls (2.42 ± 0.75 mg/dL vs. 3.73 ± 1.09 mg/dL [P = 0.000]). There was a nonsignificant inverse linear trend of association (r = −0.184; P = 0.126) between the total NMS-Quest score and SUA level in PD. Logistic regression analysis revealed hyposmia and memory impairment were significantly related to lower SUA levels (P = 0.02 and P = 0.04, respectively). Conclusion: Our study corroborates the potential of SUA as a serum biomarker in PD and a possible role in defining non-motor symptom burden. Further exploration to clarify the association and interrogate the impact of interventions is warranted.

Comparison of Mini-Mental State Examination and Montreal Cognitive Assessment Ratings Across Levels of Parkinson's Disease Severity.

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. 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. 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. 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. 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.

Does visuospatial motion perception correlate with coexisting movement disorders in Parkinson's disease?

Postural instability and balance impairment are common in Parkinson's disease (PD). Multiple factors, such as increased tone, bradykinesia, freezing of gait, posture, axial stiffness, and involuntary appendicular movements, can affect balance. The recent studies found that PD patients have abnormal perception of self-motion in vestibular domain. We asked whether measures of balance function, such as perception of one's motion, correlate with specific movement disorders seen in PD. Moving retinal image or self-motion in space triggers the perception of self-motion. We measured one's linear motion (heading) perception when subjects were moved en bloc using a moving platform (vestibular heading). Similar motion perception was generated in the visual domain (visual heading) by having the subjects view a 3D optical flow with immersive virtual reality goggles. During both tasks, the subjects reported the motion direction in the two-alternative-forced-choice paradigm. The accuracy of perceived motion direction was calculated from the responses fitted to the psychometric function curves to estimate how accurately and precisely the subjects can perceive rightward versus leftward motion (i.e., threshold and slope). Response accuracies and psychometric parameters were correlated with the disease duration, disease severity (total Unified Parkinson's Disease Rating Scale-III, UPDRS-III), and tremor, rigidity, axial, gait/posture components of UPRDS-III. We also correlated heading perception with the number of falls and subjective assessment of balance confidence using the Activities-Specific Balance Component (ABC) Scale. Accuracy, threshold, and sensitivity of vestibular heading perception significantly correlated with the disease duration and severity, particularly the tremor. Correlations were stronger for leftward heading perception in the vestibular domain. The visual heading perception was correlated with ABC Scale, especially with its items concerning optic-flow processing. There was asymmetry in leftward versus rightward vestibular heading perception. The level of asymmetry correlated with the axial component of UPDRS-III. Differences in the clinical parameters that correlate with visual versus vestibular heading perception suggest that two heading perception processes have different mechanistic underpinnings. The correlation of discordance between vestibular and visual heading perception with disease severity and duration suggests that visual function can be utilized for balance rehab in PD patients.

Weight loss and weight gain in Parkinson disease

IntroductionParkinson disease (PD) has been associated with both weight loss and gain in different stages of the disease. Our study aimed to determine the prevalence and associations with weight change over two years based on 3% and 5% weight change. MethodsIn this longitudinal analysis, weight at baseline and follow-up was used to classify patients into groups of weight loss, stable, and weight gain. Differences between these groups at baseline and then with change over time were tested. ResultsThe sample was 668 patients with mean(SD) age 66.1(10) and disease duration 5.3(5.4) years. Using 3% weight change criteria: 32.6% lost, 23.1% gained, and 55.7% had stable weight. Using 5% criteria: 22.6% lost, 15.7% gained, and 61.7% had stable weight. Age was associated with both 3% and 5% change in weight. Other associations with 5% weight change were disease duration, Total and Motor Unified Parkinson's Disease Rating Scale, Older Americans Resource and Services disability, and Hoehn & Yahr staging. The effects of 3% weight loss on Motor UPDRS, IADLs, and depression, and the effects of 5% weight loss on IADLs remained statistically significant when controlling for baseline differences in age, levodopa use, and Total UPDRS. ConclusionPD patients are more likely to experience 3% than 5% weight change and this lower threshold of weight change was associated with greater disease severity and disability over time. Attention to more subtle weight change may help identify those at greater risk of disability.

Long-Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease.

ABSTRACTBackgroundNilotinib is US Food and Drug Administration–approved for leukemia, and this open‐label study investigated the safety, tolerability, and potential clinical effects of nilotinib in medically optimized patients with Parkinson's disease.ObjectivesSafety and tolerability were the primary objectives, and clinical outcomes were exploratory.MethodsA total of 63 patients completed a 15‐month phase 2, double‐blind, placebo‐controlled study and were rerandomized 1:1 into an open‐label study of nilotinib 150 mg versus 300 mg for 12 months.ResultsNilotinib was safe and tolerated, and no adverse effects seemed to be related to the drug, and no differences in adverse events were observed between groups. Exploratory clinical outcomes showed that nilotinib 300 mg was remarkably stable from baseline to 27 months using partial and total Unified Parkinson's Disease Scale (UPDRS). Nilotinib 150 mg versus 300 mg, significantly declined using partial or the sum of UPDRS Parts I and II. There was no significant difference in nilotinib 150 mg versus 300 mg using UPDRS Part III (on levodopa) and total UPDRS Parts I to III. Subgroup analysis showed that late‐start nilotinib 150 mg significantly worsened using the sum of UPDRS Parts II + III and total UPDRS Parts I to III compared with late‐start nilotinib 300 mg. Quality of life using the Parkinson's Disease Questionnaire in nilotinib 150 mg significantly declined between 15 and 27 months compared with nilotinib 300 mg, and there was no change in cognition using the Montreal Cognitive Assessment between groups.ConclusionsThis study provides evidence that nilotinib is safe and tolerated in Parkinson's disease. The exploratory clinical data will inform an adequately powered larger study to evaluate the efficacy of nilotinib 300 mg in Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease.

The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2-PD and more severe among patients with GBA-PD; however, whether an additive phenotypical effect occurs among dual-mutation carriers requires validation. The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single-mutation presentation. Patients with PD were genotyped for the G2019S-LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA-PD, severe GBA-PD, LRRK2-PD, and LRRK2+GBA-PD. Clinical symptoms were evaluated using performance-based measures. A total of 1090 patients with idiopathic PD, 155 patients with LRRK2-PD, 155 patients with mild GBA-PD, 56 patients with severe GBA-PD, and 27 patients with LRRK2+GBA-PD participated in this study. The patients with LRRK2-PD and LRRK2+GBA-PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA-PD. Patients with LRRK2+GBA-PD were symptomatically similar to patients with LRRK2-PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation. © 2020 International Parkinson and Movement Disorder Society.

Postural Abnormalities in Parkinson's Disease: An Epidemiological and Clinical Multicenter Study.

The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with demographic and clinical variables. For this multicenter, cross-sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables. Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval [CI], 18.6%-24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%-13.3%), Pisa syndrome 8% (95% CI, 6.2%-9.9%), and anterocollis 6.5% (95% CI, 4.9%-8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with levodopa, and more likely to be treated with a combination of levodopa and dopamine agonist, took a higher daily levodopa equivalent daily dose, and had more comorbidities. Falls and back pain were more frequent in PD patients with PA than in those without PA. Multiple logistic regression models confirmed an association between PA and male gender, older age, Hoehn and Yahr stage, and total Unified Parkinson's Disease Rating Scale score. PA are frequent and disabling complications in PD, especially in the advanced disease stages.

Lower Limb Rigidity Is Associated with Frequent Falls in Parkinson's Disease.

The role of muscle rigidity as an etiological factor of falls in Parkinson's disease (PD) is poorly understood. Our objective was to determine whether lower leg rigidity was differentially associated with frequent falls in PD compared to upper limb, neck, and total rigidity measures. We examined the associations between Unified Parkinson's Disease Rating Scale-Part III (motor) rigidity subscores and the history of monthly or more frequent falls in 216 individuals with PD (age, 66 ± 10 years; 36% female; disease duration, 7 ± 5 years) with logistic regression. A total of 35 individuals were frequent fallers. Significant associations were identified between lower limb rigidity and frequent falls (P = 0.01) after controlling for age, sex, PD duration, total Unified Parkinson's Disease Rating Scale- Part III score, and presence of freezing of gait. No significant associations (P ≥ 0.14) were identified for total, arm, or neck rigidity. Lower limb rigidity is related to frequent falls in people with PD. Further investigation may be warranted into how parkinsonian rigidity could cause falls.

Long-Term Selegiline Monotherapy for the Treatment of Early Parkinson Disease.

The aim of this open-label study was to investigate the long-term safety and efficacy of selegiline as monotherapy in Japanese patients with early Parkinson disease (PD). We conducted a 56-week prospective study in patients with early PD (N = 134) who had previously completed the randomized, double-blind, placebo-controlled phase III trial of selegiline monotherapy for 12 weeks. In the present study, dosing was titrated from 2.5 to 10 mg/d in increments of 2.5 mg/d for 2 weeks. From the seventh week, the dosage was maintained at 10 mg/d until week 56. The primary outcome was any change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score (part I + II + III) from baseline. Secondary outcomes, including changes in the UPDRS subscores and safety profile, were also evaluated. Ninety-one (67.9%) patients completed the 56-week study. Treatment with selegiline significantly reduced total UPDRS score from week 4 (mean ± SD, -2.62 ± 3.83; P < 0.0001) to week 56 (-3.39 ± 9.27; P < 0.01). The peak effect was seen at week 20 (-5.79 ± 5.57; P < 0.0001). In addition, we found similar improvements in the UPDRS parts II and III scores. The incidence rate of adverse drug reactions was 44.3% (58 patients) and did not increase during the period of 10 mg selegiline administration. Long-term monotherapy with selegiline (10 mg/d) was effective and well tolerated in patients with early PD in this 56-week study.

Evaluation of RNA Blood Biomarkers in Individuals at Risk of Parkinson's Disease.

Substantial progress has been made in the discovery of blood biomarkers for Parkinson's disease (PD), a progressive neurodegenerative disease that affects more than 4 million worldwide. Olfactory dysfunction and dopamine deficits usually precede motor symptoms years before the onset of PD. A readily accessible biomarker useful for identifying patients at risk of PD is expected to accelerate clinical trials. To evaluate previously identified PD blood RNA biomarkers in a cohort of asymptomatic individuals at risk of PD. Here we tested 16 previously identified PD RNA biomarkers using quantitative PCR assays in a total of 269 blood samples at baseline from hyposmic and normosmic participants enrolled in the Parkinson's Associated Risk Syndrome study. Expression levels of four biomarkers, SOD2, PKM2, ZNF134, and ZNF160 were negatively correlated with the total Unified Parkinson's Disease Rating Scale, thus suggesting these biomarkers may be useful to stratify patients prior to the onset of motor symptoms. Levels of SOD2 were upregulated in hyposmic males compared to females, whereas levels of PKM2 were upregulated in hyposmic males compared to normosmic males and hyposmic females. Further, levels of SOD2 were upregulated in males with abnormal dopamine transporter (DAT) scans compared to females with abnormal DAT scans. These results suggest that some of these biomarkers may be useful for stratification of individuals at risk for PD and that there may be sex differences in the expression of some biomarkers. Future studies in larger longitudinal studies will be key to assessing the validity of these findings.

Impaired Bed Mobility: Quantitative Torque Analysis With Axial Inertial Sensors

To develop a practical objective method for home assessment of a patient's ability to turn in bed. Nocturnal parameters and torque of self-turning in bed from 17 PD couples were assessed and compared using a wearable axial sensor for two nights in their homes. The torque of axial rotation which indicates the ability of PD patients to turn in bed was significantly less than their spouses (p < 0.001). Significant correlations were observed between the torque of turning in bed and total unified Parkinson's Disease Rating Scale score (r = 0.71; p = 0.001), and total Nocturnal Akinesia Dystonia and Cramp score (r = 0.634; p = 0.006). Our study confirms a decreased ability in turning in PD.