Objectives Evaluate the efficacy of istradefylline in people with Parkinson’s disease with motor fluctuations, with and without dyskinesia, and characterize potential predictors for treatment-emergent dyskinesia with istradefylline.
Methods Pooled analysis of 8 phase 2b/3 trials of istradefylline (20 or 40mg/day) versus placebo.
Results Data from 2719 patients, including 56% with baseline dyskinesia, were analyzed post-hoc. The presence of baseline dyskinesia did not affect mean reductions in OFF-time, increases in ON-time without troublesome dyskinesia, or improvements in Unified Parkinson’s Disease Rating Scale motor scores associated with istradefylline treatment. Dyskinesia was reported by 17% of istradefylline-treated patients, with higher rates for women (21%), patients with BMI <18.5 kg/m2 (22%), and patients treated with COMT inhibitors plus dopamine agonists (22%) and MAO-B inhibitors (25%).
Conclusion Istradefylline treatment resulted in greater reductions in total OFF hours/day and increases in ON-time without troublesome dyskinesia versus placebo regardless of the presence or absence of pre-existing dyskinesia.
Objective
People with Parkinson's disease (PwPD) experience a gradual decline in independence in bed mobility as the disease progresses. Identifying factors associated with non-independence in daytime bed mobility is crucial for developing effective interventions to enhance independence. We investigated factors associated with non-independence in daytime bed mobility in PwPD.
Methods
This cross-sectional study included 109 PwPD (Hoehn & Yahr [HY] stage 2–4) . Patients' bed mobility ability (turning in bed, supine-to-sitting, and sitting-to-supine) was assessed during daytime and categorized into independent and non-independent groups. Potential factors associated with bed-mobility independence were evaluated, including components of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (rigidity, bradykinesia, tremor, axial symptoms), neck/trunk/hip strength, the Mini-Mental State Examination, and the Trail Making Test-A and B.
Results
The non-independent group showed significantly increased axial symptoms, increased rigidity in the upper and lower limbs and neck, increased upper limb bradykinesia, and decreased trunk flexion/extension strength in all bed-mobility tasks (p<0.05). Multivariate regression analyses showed that axial symptoms, upper limb rigidity, and trunk extension strength were highly discriminative for non-independence in turning in bed (AUC = 0.84). Similarly, upper limb rigidity and axial symptoms were predictive of non-independence in supine-to-sitting and sitting-to-supine movements (AUC = 0.78, 0.92). A significant difference in axial symptoms between HY4 subgroups was observed only in the sitting-to-supine movement.
Conclusions
Our findings indicate that axial symptoms and upper limb rigidity are key factors contributing to non-independence in daytime bed-mobility tasks among PwPD. Targeting these factors in rehabilitation may help mitigate the decline in bed-mobility independence in PwPD.
Background and Purpose Exercise is a critical non-pharmacological intervention for Parkinson’s disease (PD); however, comparative evidence on the efficacy of different exercise modalities is limited. This study aimed to compare the effects of tai chi, strength training, yoga, and home-based exercises on motor in patients with Parkinson’s disease (PD).
Subject and Methods In this multicenter, open-label, randomized clinical trial, 99 patients with PD were allocated to one of four exercise interventions: tai chi, strength training, yoga, or home-based exercises. Each intervention consisted of 12 weeks of supervised sessions, followed by 12 weeks of independent practice. The primary outcomes included the MDS-UPDRS Part III and timed up-and-go (TUG) test parameters. The secondary outcomes assessed included physical activity (SPPB and 6 MWT), balance (Mini-BEST), and freezing of gait (NFOGQ).
Results Home exercise and tai chi demonstrated significant improvements in the MDS-UPDRS Part III scores over 24 weeks. 6 minutes walking test was improved by home exercises, tai chi, and MiniBest was enhanced by strength exercises and yoga. The total duration and forward movement of TUG and turning duration measuring by wearable sensor were markedly improved in yoga group.
Conclusion Our results support that various in adherence and outcomes of exercise have been observed in real-world setting even though effectiveness of exercise is well established. These findings highlighted the importance of tailoring exercise regimens considering individual patients in PD management
Objectives A lack of standardized methods for evaluating postural abnormalities hinders treatment progress. The role of pelvic lateral shift (PLS) in patients with Parkinson’s disease (PwP) exhibiting lateral trunk flexion (LTF) remains unclear. We hypothesized that PLS is related to LTF and investigated its characteristics and relationship to LTF angle.
Methods PwP attending outpatient rehabilitation (March 2018–March 2023) were assessed using still images. PLS direction, its relationship with LTF angle, and LTF angle by PLS side were analysed.
Results Among 158 patients, PLS was contralateral in 80 (50.6%), ipsilateral in 43 (27.2%), and absent in 35 (22.2%). In contralateral PLS, but not ipsilateral, PLS angle correlated with LTF angle (r=0.48, p<0.001). LTF angle was greater in contralateral (8.5±9.6°) than ipsilateral shift (2.8±4.2°, p<0.001).
Conclusions Because of the positive relationship between LTF angle and contralateral shift angle, evaluation criteria that include PLS are needed for PwP with LTF.
Purpose
To investigate shoulder function and muscle alterations in patients with Parkinson’s disease (PD) and to determine their association with spinopelvic parameters and clinical status.
Methods
This prospective cohort study included 62 PD patients (divided into PIGD [n=30] and non-PIGD [n=32] groups) and 35 controls. The American Shoulder and Elbow Surgeons score (ASES), range of motion (ROM), and shoulder muscle stiffness were assessed for each group. Data on clinical demographics, PD disease severity, and shoulder parameters were extracted and analyzed.
Results
The PIGD group had significantly lower ASES total and sub-scores (all p < 0.05) compared to the controls. Both PIGD and non-PIGD groups demonstrated reduced abduction and forward flexion (all p < 0.05) compared to controls. The PIGD group also had decreased external rotation compared to the non-PIGD group and controls (all p < 0.05). Infraspinatus muscle stiffness was higher in the PIGD group than in controls (p = 0.012). Correlation analysis revealed that shoulder condition was significantly associated with PD disease severity and PIGD score, while muscle stiffness was linked to spinopelvic alignment and PIGD score. Various clinical factors, including PD disease severity, PIGD score, tremor score, and spinopelvic alignment, significantly correlated with shoulder ROM.
Conclusion
PD patients experienced shoulder dysfunction in various ways, including decreased ASES scores, limited ROM, and increased shoulder muscle stiffness. Our study highlighted the impact of PD motor subtype, disease severity, and spinopelvic alignment on the development of shoulder dysfunction, offering deeper insights into the pathophysiological basis of shoulder disorders in PD.
Natalie E Allen, Lina Goh, Colleen G Canning, Catherine Sherrington, Lindy Clemson, Jacqueline CT Close, Stephen R Lord, Simon J G Lewis, Simone Edwards, Susan Harkness, Roslyn Savage, Lyndell Webster, Genevieve Zelma, Serene S Paul
J Mov Disord. 2025;18(2):149-159. Published online March 14, 2025
Objective Mobility limitations and falls are common in people with Parkinson’s disease (PwP). Compared with exercise alone, a tailored, multidomain intervention has the potential to be more effective in improving mobility safety and preventing falls. This study aimed to explore the feasibility and potential effectiveness of a multidomain fall prevention intervention (Integrate) designed for PwP who experience frequent falls.
Methods The home-based intervention was delivered over a span of 6 months by occupational therapists and physiotherapists. The personalized intervention included home fall hazard reduction, exercise, and safer mobility behavior training. The participants received 8 to 12 home visits and were supported by care-partners (when necessary) to participate in the intervention.
Results Twenty-nine people (recruitment rate: 49%; drop-out rate: 10%) with moderate to advanced Parkinson’s disease, a history of recurrent falls, and mild to moderate cognitive impairment participated in the study, with 26 people completing the study. A moderate-to-high adherence to the intervention was observed, and there were no adverse events related to the intervention. Twenty-one (81%) participants met or exceeded their safer mobility goal based on the Goal Attainment Scale. The participants exhibited a median 1.0-point clinically meaningful improvement according to the Short Physical Performance Battery. An exploratory analysis revealed that fall rates were reduced by almost 50% in the 6-month follow-up period (incidence rate ratio: 0.51; 95% confidence interval 0.28–0.92).
Conclusion A multidomain occupational therapy and physiotherapy intervention for PwP experiencing recurrent falls was feasible and appeared to improve mobility safety. A randomized trial powered to detect the effects of the intervention on falls and mobility is warranted.
Objective We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson’s disease.
Methods Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs.
Results During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson’s disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a nonlinear increasing (J-shaped) trend.
Conclusion Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.
Objective The outcomes of motor and nonmotor features of Parkinson’s disease (PD) following deep brain stimulation (DBS) vary among its subtypes. We tested whether preoperative motor subtyping using the modified tremor/postural instability and gait difficulty ratio (T/P ratio) could indicate the short-term motor, nonmotor and quality of life (QOL) outcomes of subthalamic nucleus (STN) DBS.
Methods In this prospective study, 39 consecutive STN DBS patients were assessed in the drug-OFF state before surgery and subtyped according to the T/P ratio. Patients were reassessed 6 months after surgery in the stimulation ON-drug-OFF state, and the percentage changes in motor, nonmotor and QOL scores (Parkinson’s Disease Quality of Life Questionnaire [PDQ-39]) were calculated.
Results The modified T/P ratio was moderately and positively correlated with the percentage change in the Unified Parkinson’s Disease Rating Scale III score in the OFF state, the sum of cardinal motor signs, the Non-Motor Symptom Scale score, and QOL (PDQ-39).
Conclusion Preoperative PD motor subtyping can be used as an indicator of the short-term outcomes of STN DBS in PD patients.
Objective Camptocormia contributes to vertical gait instability and, at times, may also lead to forward instability in experimental settings in Parkinson’s disease (PD) patients. However, these aspects, along with compensatory mechanisms, remain largely unexplored. This study comprehensively investigated gait instability and compensatory strategies in PD patients with camptocormia (PD+CC).
Methods Ten PD+CC patients, 30 without camptocormia (PD-CC), and 27 healthy controls (HCs) participated. Self-paced gait tasks were analyzed using three-dimensional motion capture systems to assess gait stability as well as spatiotemporal and kinematic parameters. Unique cases with pronounced forward gait stability or instability were first identified, followed by group comparisons. Correlation analysis was performed to examine associations between trunk flexion angles (lower/upper) and gait parameters. The significance level was set at 0.05.
Results Excluding one unique case, the PD+CC group presented a significantly lower vertical center of mass (COM) position (p=0.019) increased mediolateral COM velocity (p=0.004) and step width (p=0.013), compared to the PD-CC group. Both PD groups presented greater anterior‒posterior margins of stability than did the HCs (p<0.001). Significant correlations were found between lower/upper trunk flexion angles and a lower vertical COM position (r=-0.690/-0.332), as well as increased mediolateral COM velocity (r=0.374/0.446) and step width (r=0.580/0.474).
Conclusion Most PD+CC patients presented vertical gait instability, increased fall risk, and adopted compensatory strategies involving greater lateral COM shift and a wider base of support, with these trends intensifying as trunk flexion angles increased. These findings may guide targeted interventions for gait instability in PD+CC patients.
Objective This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance.
Methods We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations.
Results A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes.
Conclusion Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.
Non-motor fluctuations (NMFs) in Parkinson’s disease (PD) significantly affect patients’ well-being. Despite being identified over two decades ago, NMFs remain largely underrecognized, undertreated, and poorly understood. While they are often temporally associated with motor fluctuations (MFs) and can share common risk factors and pathophysiologic mechanisms, NMFs and MFs are currently considered distinct entities. The prevalence and severity of NMFs, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMFs on PD patients’ quality of life underscores the importance of further investigations via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMFs, ultimately enhancing clinicians’ diagnostic and treatment options in routine clinical practice.
Post hoc exploratory analysis of the effect of foslevodopa/foscarbidopa continuous subcutaneous infusion on nocturia in patients with Parkinson’s disease K. Ray Chaudhuri, Manon Bouchard, Eric Freire-Alvarez, Rajesh Pahwa, Lars Bergmann, Resmi Gupta, Pavnit Kukreja, Megha B. Shah, Stuart H. Isaacson Clinical Parkinsonism & Related Disorders.2025; : 100330. CrossRef
Objective Oculomotor impairment is an important diagnostic feature of progressive supranuclear palsy (PSP) and PSP subtypes. We assessed the role of video-oculography (VOG) in confirming clinically suspected slow saccades in PSP and differentiating PSP from Parkinson’s disease (PD). We also measured the correlation of both saccadic velocity and latency in PSP patients with scores on the PSP Rating Scale, Montreal Cognitive Assessment, and frontal assessment battery. We assessed the frequency of apraxia of eyelid opening (ALO) and reflex blepharospasm in PSP and PD patients.
Methods A total of 112 PSP patients with slow saccades but not gaze palsy, 50 PD patients, and 50 healthy controls (HCs) were recruited. The Movement Disorders Society task force-PSP and PD criteria were used for the diagnoses. All the subjects underwent VOG.
Results Horizontal and vertical saccadic velocities and latencies differentiated PSP patients from PD patients and HCs (p<0.001). Vertical saccadic velocity and latency accurately differentiated PSP with predominant parkinsonism (PSP-P) patients from PD patients (p<0.001 and 0.012, respectively). A couple of vertical and horizontal saccadic velocities differentiated PSP-Richardson’s syndrome (PSP-RS) patients from PSP-P patients (vertical velocity of left eye: p=0.024; horizontal velocity of right eye: p=0.030). In vertical gaze, the mean velocity cutoff showed good sensitivity and specificity in differentiating PSP patients from HCs and PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse global cognitive and frontal dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.
Conclusion VOG is useful for confirming slow saccades in PSP-RS and PSP-P patients and for differentiating PSP-P patients from PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse cognitive dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.
Objective Gait speed is regulated by varying gait parameters depending on the diverse contexts of the environment. People with Parkinson’s disease (PwPD) have difficulty adapting to gait control in their environment; however, the relationships between gait speed and spatiotemporal parameters in free-living environments have not been clarified. This study aimed to compare gait parameters according to gait speed in clinics and free-living environments.
Methods PwPD were assessed at the clinic and in a free-living environment using an accelerometer on the lower back. By fitting a bimodal Gaussian model to the gait speed distribution, gait speed was divided into lower and higher speeds. We compared the spatiotemporal gait parameters using a 2 × 2 (environment [clinic/free-living] × speed [lower/higher]) repeated-measures analysis of variance. Associations between Parkinson’s disease symptoms and gait parameters were evaluated using Bayesian Pearson’s correlation coefficients.
Results In the 41 PwPD included in this study, spatiotemporal gait parameters were significantly worse in free-living environments than in clinics and at lower speeds than at higher speeds. The fit of the walking speed distribution to the bimodal Gaussian model (adjustability of gait speed) in free-living environments was related to spatiotemporal gait parameters, severity of Parkinson’s disease, number of falls, and quality of life.
Conclusion The findings suggest that gait control, which involves adjusting gait speed according to context, differs between clinics and free-living environments in PwPD. Gait assessments for PwPD in both clinical and free-living environments should interpret gait impairments in a complementary manner.
Ilaria Guarracino, Christian Lettieri, Massimo Mondani, Stanislao D’Auria, Giovanni Sciacca, Flavia Lavezzi, Miran Skrap, Serena D’Agostini, Gian Luigi Gigli, Mariarosaria Valente, Barbara Tomasino
J Mov Disord. 2024;17(4):442-446. Published online September 23, 2024
Objective We monitored cognition in 14 Parkinson’s disease (PD) patients during deep brain stimulation (DBS) surgery when the electrode was positioned at the target subthalamic nucleus (STN) (i.e., the STN motor area).
Methods We present the DBS-real-time neuropsychological testing (DBS-RTNT) protocol and our preliminary experience with it; we also compared the intraoperative patient performance with the baseline data.
Results Compared with the baseline data, patients undergoing DBS-RTNT in the target area demonstrated a significantly decreased performance on some tasks belonging to the memory and executive function domains. Patients undergoing right hemisphere DBS-RTNT had significantly lower short-term memory and sequencing scores than did patients undergoing left hemisphere DBS-RTNT.
Conclusion PD patient cognitive performance should be monitored during DBS surgery, as STN-DBS may induce changes. These preliminary data contribute to improving our understanding of the anatomo-functional topography of the STN during DBS surgery, which will enable the identification of the best site for producing positive motor effects without causing negative cognitive and/or emotional changes in individual patients in the future. In principle, medications (i.e., patients who underwent surgery in a levodopa-off state) could have influenced our results; therefore, future studies are needed to address the possible confounding effects of levodopa use.