Search Results (109)

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder that impairs mobility. Treadmill training (TT) is a common rehabilitation strategy for improving gait parameters in individuals with PD. This systematic review evaluated the effectiveness of TT in improving motor function, walking ability, and overall functional mobility in PD patients. Methods: We compared TT to other forms of gait and motor rehabilitation, including conventional and robotic gait training. Trials that compared a treadmill training group with a non-intervention group were excluded from this review. We searched multiple databases for RCTs involving Parkinson’s patients until January 2025. The primary outcomes were motor function (UPDRS-III) and walking ability (6 MWT and TUG test). Results: We identified 285 articles; 199 were excluded after screening. We assessed the full text of 86 articles for eligibility, and 13 RCTs met the inclusion criteria. Some of them were included in the meta-analysis. The TT group showed a significant improvement in UPDRS-III scores [mean difference (MD): −1.36 (95% CI: −2.60 to −0.11)] and greater improvement in TUG performance [MD, −1.75 (95% CI: −2.69 to −0.81)]. No significant difference in walking capacity as assessed through the 6 MWT was observed [MD: 26.03 (95% CI: −6.72 to 58.77). Conclusions: The current study suggests that TT is effective in improving the motor symptoms and functional mobility associated with PD. Further studies are needed to develop protocols that consider the patients’ clinical characteristics, disease stage, exercise tolerance, and respiratory function. Full article

Background/Objectives: The study aims to identify key cognitive and non-cognitive variables (e.g., clinical, neuroimaging, and genetic data) predicting cognitive decline in Parkinson’s disease (PD) patients using machine learning applied to a sample (N = 618) from the Parkinson’s Progression Markers Initiative database. Traditional research has mainly employed explanatory approaches to explore variable relationships, rather than maximizing predictive accuracy for future cognitive decline. In the present study, we implemented a predictive framework that integrates a broad range of baseline cognitive, clinical, genetic, and imaging data to accurately forecast changes in cognitive functioning in PD patients. Methods: An artificial neural network was trained on baseline data to predict general cognitive status three years later. Model performance was evaluated using 5-fold stratified cross-validation. We investigated model interpretability using explainable artificial intelligence techniques, including Shapley Additive Explanations (SHAP) values, Group-Wise Feature Masking, and Brute-Force Combinatorial Masking, to identify the most influential predictors of cognitive decline. Results: The model achieved a recall of 0.91 for identifying patients who developed cognitive decline, with an overall classification accuracy of 0.79. All applied explainability techniques consistently highlighted baseline MoCA scores, memory performance, the motor examination score (MDS-UPDRS Part III), and anxiety as the most predictive features. Conclusions: From a clinical perspective, the findings can support the early detection of PD patients who are more prone to developing cognitive decline, thereby helping to prevent cognitive impairments by designing specific treatments. This can improve the quality of life for patients and caregivers, supporting patient autonomy. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder commonly marked by upper limb tremors that interfere with daily activities. Wearable devices, such as smartwatches, represent a promising solution for continuous and objective monitoring in PD. This study aimed to develop and validate a tremor-detection algorithm using smartwatch sensors. Data were collected from 21 individuals with PD and 27 healthy controls using both a commercial inertial measurement unit (G-Sensor, BTS Bioengineering, Italy) and a smartwatch (Apple Watch Series 3). Participants performed standardized arm movements while sensor signals were synchronized and processed to extract relevant features. Statistical analyses assessed discriminant and concurrent validity, reliability, and accuracy. The algorithm demonstrated moderate to strong correlations between smartwatch and commercial IMU data, effectively distinguishing individuals with PD from healthy controls showing associations with clinical measures, such as the MDS-UPDRS III. Reliability analysis demonstrated agreement between repeated measurements, although a proportional bias was noted. Power spectral density (PSD) analysis of accelerometer and gyroscope data along the x-axis successfully detected the presence of tremors. These findings support the use of smartwatches as a tool for detecting tremors in PD. However, further studies involving larger and more clinically impaired samples are needed to confirm the robustness and generalizability of these results. Full article

Background: Metabolic syndrome and Parkinson’s disease have common pathophysiological denominators. This study aimed to investigate how metabolic syndrome contributes to Parkinson’s disease progression, as well as the genetic traits shared by PD and MetS. Methods: Four hundred and twenty-three newly diagnosed drug-naïve PD patients were analyzed from the Parkinson’s Progression Markers Initiative (PPMI) database. We compared longitudinal changes in the total and subscale scores of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) between PD patients with and without metabolic syndrome over a five-year follow-up. We assessed the frequency of PD-associated genetic variants in both groups. Results: At baseline, Parkinson’s patients with MetS were typically men (p < 0.01) and older (p = 0.04), with a higher Hoehn and Yahr score (p = 0.01) compared with their counterparts without MetS. They showed higher Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total scores at baseline and in follow-up years 2, 3, 4, and 5 (all p-values < 0.05) as analyzed by the Generalized Estimating Equation model. These differences were primarily driven by elevated motor scores (MDS-UPDRS Part III) (p < 0.01). MetS was associated with a higher frequency of the ZNF646.KAT8.BCKDK_rs14235 variant and a lower frequency of the NUCKS1_rs823118 and CTSB_rs1293298 variants. Conclusions: PD patients with MetS had worse motor symptomatology. Both conditions appear to share genetic susceptibility, involving genes related to lipid metabolism (BCKDK), autophagy and inflammation (CTSB), and chromatin regulation (NUCKS1). Full article

Background/Objective: Parkinson’s disease (PD) is characterized by motor and cognitive impairments that significantly affect quality of life. Robotic-assisted therapies, such as the AMADEO^® system, have shown potential in rehabilitating upper limb function but are underexplored in PD. This study aimed to assess the effects of Robotic-Assisted Therapy (RAT) compared to Conventional Physical Therapy (CPT) on cognitive, motor, and functional outcomes in PD patients. Methods: A single-blind, randomized controlled trial was conducted with PD patients allocated to RAT or CPT. Participants were assessed at baseline (T0) and post-intervention (T1) using measures including MoCA, FAB, UPDRS-III, 9-Hole Peg Test, FMA-UE, FIM, and PDQ-39. Statistical analyses included ANCOVA and regression models. Results: RAT led to significant improvements in global cognition (MoCA, p < 0.001) and executive functioning (FAB, p = 0.0002) compared to CPT. Motor function improved, particularly in wrist and hand control (FMA-UE), whereas changes in fine motor dexterity (9-Hole Peg Test) were less consistent and did not reach robust significance. No significant improvements were observed in broader quality of life domains, depressive symptoms, or memory-related cognitive measures. However, quality of life improved significantly in the stigma subdomain of the PDQ-39 (p = 0.0075). Regression analyses showed that baseline motor impairment predicted cognitive outcomes. Conclusions: RAT demonstrated superior cognitive and motor benefits in PD patients compared to CPT. These results support the integration of robotic rehabilitation into PD management. Further studies with larger sample sizes and long-term follow-up are needed to validate these findings and assess their sustainability. Full article

Background: Parkinson Disease (PD) is a progressive neurodegenerative disorder. Current therapeutic trials investigate treatments that can potentially modify the disease course. Testing their efficiency requires outcome assessments that are relevant to patients’ daily lives, which include gait and balance. Home-based examinations may enhance patient compliance and, in addition, produce more reliable results by assessing patients more regularly in their familiar surroundings. Objective: The objective of this pilot study was to assess the feasibility of a home-based outcome assessment designed to video record the Timed up and Go (vTUG) test via a study-specific smartphone app for patients with PD. Methods: 28 patients were recruited and asked to perform at home each week a set of three consecutive vTUG tests, over a period of 12 weeks using an app. The videos were subjected to a manual review to ascertain the durations of the individual vTUG phases, as well as to identify any errors or deviations in the setup that might have influenced the result. To evaluate the usability and user-friendliness of the vTUG and app, the System Usability Scale (SUS) and User Experience Questionnaire (UEQ) were administered to patients at the study end. Results: 19 patients completed the 12-week study, 17 of which recorded 10 videos or more. A total of 706 vTUGs with complete timings were recorded. Random Forest Regression yielded “time to walk up” as the most important segment of the vTUG for predicting the total time. Variance of vTUG total time was significantly higher between weeks than it was between the three consecutive vTUGs at one time point [F(254,23) = 6.50, p < 0.001]. The correlation between vTUG total time and UPDRS III total score was weak (r = 0.24). The correlation between vTUG and a derived gait subscore (UPDRS III items 9–13) was moderate (r = 0.59). A linear mixed-effects model revealed a significant effect of patient-reported motion status on vTUG total time. Including additional variables such as UPDRS III gait subscore, footwear and chairs used further improved the model fit. Conclusions: Assessment of gait and balance by home-based vTUG is feasible. Factors influencing the read-out were identified and could be better controlled for future use and longitudinal trials. Full article

Objective: We aimed to analyze the real-world use of COMT inhibitors associated with levodopa in patients with Parkinson’s disease (PD) who present early fluctuations and to explore whether early COMT inhibition optimizes treatment outcomes. Methods: REONPARK is an ongoing 2-year prospective observational study. We included patients diagnosed with PD who presented signs of end-of-dose motor fluctuations for <2 years and started COMT inhibitors according to clinical practice. Outcomes included the clinician and patient global impression of change (CGI-C, PGI-C), the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Parkinson’s Disease Questionnaire-8 (PDQ-8), Non-Motor Symptoms Scale (NMSS), 19-Symptom Wearing-off Questionnaire (WOQ-19), and safety. We present a pre-planned interim analysis (cut-off date 3 July 2023) of patients who completed the first 3 months of follow-up. Results: Seventy patients were analyzed (mean levodopa dose at inclusion 484.8 mg; duration of motor fluctuations 0.6 years). In all cases, COMT inhibition was initiated with opicapone, and 81% maintained a stable levodopa dose at 3 months. After 3 months of treatment with opicapone, 73.5% and 62.8% of patients improved on CGI-C and PGI-C, respectively. MDS-UPDRS scores improved significantly with a mean change from baseline of −3.3 ± 7.7 (p < 0.001) for Part III and −1.3 ± 1.7 (p < 0.001) for Part IV. The mean OFF time decreased from 3.7 ± 2.6 h at baseline to 2.2 ± 2.3 h, and 20.6% of patients no longer experienced OFF periods. Patients experiencing no impact of fluctuations increased from 10% to 45.6%. Conclusions: In PD patients with early fluctuations, three months of opicapone reduced the OFF time and improved functional outcomes, suggesting potential benefits in the early stages. Full article

Background and Objectives: Robotic exoskeletons show potential in PD gait rehabilitation. But the optimal assistive force and its equivalence to clinical gold standard assessments are unclear. This study aims to explore the clinical equivalence of the lower limb exoskeleton in evaluating PD patients’ gait disorders and find the best assistive force for clinical use. Methods: In this prospective controlled trial, 60 PD patients (Hoehn and Yahr stages 2–4) and 60 age-matched controls underwent quantitative gait analysis using a portable exoskeleton (Relink-ANK-1BM) at four assistive force levels (0 N, 40 N, 80 N, 120 N). Data from 57 patients and 57 controls were analyzed with GraphPad Prism 10. Different statistical tests were used based on data distribution. Results: ROC analysis showed that exoskeleton-measured velocity had the strongest power to distinguish PD patients from controls (AUC = 0.9198, p < 0.001). Other parameters also had high reliability and validity. There was a strong positive correlation between UPDRS-III lower extremity sub-score changes and gait velocity changes in PD patients (r = 0.8564, p < 0.001). The 80 N assistive force led to the best gait rehabilitation, with a 58% increase in gait velocity compared to unassisted walking (p < 0.001). Conclusions: 80 N is the optimal assistive threshold for PD gait rehabilitation. The wearable lower limb exoskeleton can be an objective alternative biomarker to UPDRS-III, enabling personalized home-based rehabilitation. Full article

Background/Objectives: Parkinson’s disease (PD) and hypertension are often coexistent conditions that interact in entwined ways at various levels. Cardiovascular autonomic dysfunction (CAD), a non-motor feature of PD occurring across all stages, alters blood pressure (BP) regulation. Methods: We conducted a cross-sectional study enrolling patients with PD and primary hypertension, without diabetes mellitus or other causes of secondary CAD, aiming to characterize BP profiles/patterns by ambulatory BP monitoring. We also sought associations between different CAD phenotypes and PD characteristics, disability, and cardiovascular comorbidities. Results: We included 47 patients with a median age of 71 years, PD duration of 9 years, and Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III score of 40. Diurnal and nocturnal BP values were within the reference range, but BP load was excessive. Almost one-third had neurogenic orthostatic hypotension (OH) and 80% were non-dippers. The overall burden of non-motor symptoms was significant in these phenotypes. Patients with neurogenic OH were more prone to constipation, anxiety, and urinary problems, whereas gustatory dysfunction, loss of libido, and erectile dysfunction were more frequently reported by non-dippers. No significant differences with regard to cognitive decline were identified in subjects with and without neurogenic OH. Neurogenic OH was symptomatic in 78% of the cases, whereas 56% of those with orthostatic symptoms did not have OH at repeated measurements. Conclusions: Neurogenic OH is an independent predictor of disability in patients with PD and hypertension, after adjusting for PD duration, Hoehn and Yahr stage, levodopa equivalent daily dose (LEDD), and Montreal Cognitive Assessment (MoCA) score. Full article

Background and Objectives: Virtual reality (VR)-based interventions provide immersive and interactive environments that can enhance motor learning and deliver real-time feedback, offering potential advantages over conventional therapies. This systematic review evaluated the impact of non-immersive and immersive VR exergaming interventions versus conventional therapy on balance in Parkinson’s disease (PD) through a detailed analysis of randomized controlled trials (RCTs). Materials and Methods: A comprehensive search was conducted across the PubMed, Lilacs, IBECS, CENTRAL, Web of Science (WOS), EBSCOHost, and SciELO databases. Article selection and duplicate removal were managed using Rayyan QCRI. The quality of the evidence was assessed using the GRADE system. Results: From an initial screening of 100 studies, 58 underwent title and abstract screening. After full-text evaluation, 11 RCTs met the inclusion criteria, involving 518 participants with PD (average age: 67.3 years; 67.95% men). The balance outcomes were primarily measured using the Berg balance scale (BBS), employed in most studies (n = 9). The pooled analysis demonstrated a significant improvement in the balance scores for the experimental groups compared to the controls, with a standardized mean difference (SMD) of 0.58 [95% CI: 0.07, 1.09, p = 0.03]. However, the heterogeneity was substantial (I² = 77%). The analysis of the six-minute walking test (6 MWT), as another outcome of four articles, revealed a mean difference of 32.99 m [95% CI: −8.02, 74.00], but the effect was not statistically significant (p = 0.11). The heterogeneity for this outcome was moderate (I² = 41%), indicating some variability across studies. Alternative tools, such as the Tinetti Performance-Oriented Mobility Assessment (POMA) scale, the UPDRS III, and the sensory organization test (SOT), were also evaluated where possible. Conclusions: VR-based interventions offer promise for improving balance in Parkinson’s disease, enhancing rehabilitation engagement. Their integration into clinical practice could complement conventional therapy. However, further research is needed to optimize protocols, standardize parameters, and maximize their impact on mobility, independence, and quality of life. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder that manifests through motor and non-motor symptoms. Understanding the alterations in brain connectivity associated with PD remains a challenge that is crucial for enhancing diagnosis and clinical management. Methods: This study utilized Magnetoencephalography (MEG) to investigate brain connectivity in PD patients compared to healthy controls (HCs) by applying eigenvector centrality (EC) measures across different frequency bands. Results: Our findings revealed significant differences in EC between PD patients and HCs in the alpha (8–12 Hz) and beta (13–30 Hz) frequency bands. To go into further detail, in the alpha frequency band, PD patients in the frontal lobe showed higher EC values compared to HCs. Additionally, we found statistically significant correlations between EC measures and clinical impairment scores (UPDRS-III). Conclusions: The proposed results suggest that MEG-derived EC measures can reveal important alterations in brain connectivity in PD, potentially serving as biomarkers for disease severity. Full article

Background: This study aimed to explore the potential associations between voice metrics of patients with PD and their motor symptoms. Methods: Motor and vocal data including the Unified Parkinson’s Disease Rating Scale part III (UPDRS-III), Harmonic–Noise Ratio (HNR), jitter, shimmer, and smoothed cepstral peak prominence (CPPS) were analyzed through exploratory correlations followed by univariate linear regression analyses. We employed these four voice metrics as independent variables and the total and sub-scores of the UPDRS-III as dependent variables. Results: Thirteen subjects were included, 76% males and 24% females, with a mean age of 62.9 ± 10.1 years, and a median Hoehn and Yahr stage of 2.3 ± 0.7. The regression analysis showed that CPPS is associated with posture (UPDRS-III posture scores: β = −0.196; F = 10.0; p = 0.01; R² = 0.50) and UPDRS-III postural stability scores (β = −0.130; F = 5.57; p = 0.04; R² = 0.35). Additionally, the associations between CPPS and rapid alternating movement (β = −0.297; p = 0.07), rigidity (β= −0.36; p = 0.11), and body bradykinesia (β = −0.16; p = 0.13) showed a trend towards significance. Conclusion: These findings highlight the potential role of CPPS as a predictor of postural impairments secondary to PD, emphasizing the need for further investigation. Full article

Objectives: Our aim was to evaluate the possible long-term cerebral deposition of amyloid-β in patients with PD treated with subthalamic nucleus deep brain stimulation (STN-DBS) and its possible influence on axial and cognitive variables. Methods: Consecutive PD patients treated with bilateral STN-DBS with a long-term follow-up were included. The amyloid-β deposition was evaluated postoperatively through an 18F-flutemetamol positron emission tomography (PET) study. Axial symptoms were assessed using a standardized clinical–instrumental approach. The speech was assessed by perceptual and acoustic analysis, while gait was assessed by means of the instrumented Timed Up and Go test (iTUG). Motor severity was evaluated by applying the UPDRS part III score and subscores, while cognitive functions were assessed through a complete neuropsychological assessment. Different stimulation and drug conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication conditions (single- and dual-task). Results: In total, 19 PD patients (male: 11; age: 63.52 years; on-stimulation/on-medication UPDRS-III: 17.05) with a five-year postoperative follow-up were included. The amyloid-β deposition was found in 21% of patients (4/19) with a prevalent involvement of prefrontal, limbic, and parietal areas. Compared with patients without amyloid-β deposition, PD patients with positive 18F-flutemetamol in the PET study showed a higher preoperative UPDRS-I (p = 0.037) score. Conclusions: Our results suggest that in the long term, after STN-DBS, a significant percentage of PD patients may present brain amyloid-β deposition. However, larger samples are needed to evaluate the possible role of amyloid-β deposition in the development of axial and cognitive alterations after surgery. Full article

Introduction: Randomized clinical trials should be complemented with data from real-world studies. We report our long-term experience with safinamide in a movement disorders unit. Methods: This retrospective study included patients with Parkinson’s disease (PD) treated with safinamide in our unit from February 2016 to May 2022 under routine clinical practice. Assessments included the Hoehn and Yahr (HY) stage, unified Parkinson’s disease rating scale (UPDRS) part III score, levodopa equivalent daily dose (LEDD), LEDD for dopamine agonists, and safinamide treatment discontinuation. Results: We included 180 patients with a median age of 74 years (IQR 11), and the majority (90.6%) had an HY stage of ≤2. After a median follow-up of 40 months (IQR 34), 14 patients discontinued treatment with safinamide (7.8%, 95% CI 4.7 to 12.6). Among the 166 patients who remained on safinamide, the UPDRS III score was stable (10 (IQR 9) vs. 9 (IQR 13), p = 0.455). The LEDD significantly increased from a median of 300 mg to 500 mg (p < 0.001), whereas the LEDD for dopamine agonists did not significantly increase. A subgroup of 89 patients who did not require dopamine agonists during follow-up showed stable UPDRS III score (10 (IQR 7) vs. 9 (IQR 14); p = 0.923), with a significant LEDD increase (300 mg to 400 mg, p < 0.001). Conclusions: Our results support the long-term effectiveness and tolerability of safinamide in patients with PD in clinical practice. Full article

Background and Purpose: This pilot randomized controlled trial evaluated the effects of 12 sessions of patient-specific adaptive dynamic cycling (PSADC) versus non-adaptive cycling (NA) on motor function and mobility in individuals with Parkinson’s disease (PD), using inertial measurement unit (IMU) sensors for objective assessment. Methods: Twenty-three participants with PD (13 in the PSADC group and 10 in the NA group) completed the study over a 4-week period. Motor function was measured using the Kinesia™ sensors and the MDS-UPDRS Motor III, while mobility was assessed with the TUG test using OPAL IMU sensors. Results: The PSADC group showed significant improvements in MDS-UPDRS Motor III scores (t = 5.165, p < 0.001) and dopamine-sensitive symptoms (t = 4.629, p = 0.001), whereas the NA group did not improve. Both groups showed non-significant improvements in TUG time. IMU sensors provided continuous, quantitative, and unbiased measurements of motor function and mobility, offering a more precise and objective tracking of improvements over time. Conclusions: PSADC demonstrated enhanced treatment effects on PD motor function compared to NA while also reducing variability in individual responses. The integration of IMU sensors was essential for precise monitoring, supporting the potential of a data-driven, individualized exercise approach to optimize treatment outcomes for individuals with PD. Full article