Search Results (139)

Many people with Parkinson’s disease (PwPD) lack optimal care due to limited access to neurologists and a reliance on subjective rating scales for treatment decisions. The Ceraxis Insight platform was designed to provide quantitative measures of the cardinal motor symptoms of Parkinson’s disease (PD) through self-administered assessments performed using a tablet paired with a sensor-embedded stylus. The aim of this study was to assess the validity of the Ceraxis Insight outcome metrics against clinical gold-standard measures of PD motor symptoms. Nineteen PwPD completed a clinical examination and the nine Ceraxis Insight assessment modules. Quantitative performance metrics were calculated from the platform’s IMU, force transducer, and touchscreen inputs. Mixed-effect models and correlation analyses determined that multiple quantitative metrics from the Ceraxis Insight modules significantly predicted (p < 0.05) and were significantly correlated (correlation coefficients > 0.70) with the MDS-UPDRS III total score, bradykinesia, tremor, rigidity, and postural instability and gait difficulty sub-scores. Logistic regression models determined that multiple Ceraxis Insight metrics discriminated between ON- and OFF-deep brain stimulation (DBS) conditions, with Area Under the Receiver Operating Characteristic Curve (AUC) values exceeding 0.70. The Ceraxis Insight platform provides a validated, objective assessment of PD motor symptoms that may be performed within clinical or remote settings for data-driven evaluation and treatment. Full article

Variants in the glucocerebrosidase gene (GBA1) are the predominant genetic risk factor for Parkinson’s disease (PD), often accelerating disease progression. While biological sex modulates PD progression, the longitudinal association between rasagiline (a monoamine oxidase-B [MAO-B] inhibitor) and motor outcomes in GBA1-associated Parkinson’s disease (GBA1-PD) remains unclear. This retrospective cohort study (2019–2026) analyzed 259 patients with PD (106 females, 153 males) with a median follow-up of 1.56 years to evaluate the association between rasagiline use and motor decline, emphasizing sex-stratified outcomes. Motor progression was evaluated using the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS-III). Rates of change were calculated using sex-stratified Generalized Estimating Equations models, with adjustment for age at diagnosis to evaluate treatment effects and sex-specific associations. Among 259 patients, rasagiline use was associated with a significantly slower annual rate of motor decline (Slope Difference: −0.95; p = 0.03). In the GBA1-PD subgroup, females using rasagiline exhibited a clinically relevant slower rate of progression (approximately 1 point/year on the MDS-UPDRS-III) compared with non-users, although not statistically significant (p = 0.08); no association was observed in males. These findings suggest a potential sex-specific association of rasagiline with motor progression in GBA1-PD. Results highlight the importance of sex-stratified analyses to support personalized therapeutic approaches for PD genetic variants. Full article

Pupil response may be a useful biomarker in Parkinson’s disease (PD) due to links with autonomic function and cognitive load. However, research has focused on static tasks, missing functional demands during real-world activities like walking. Methods: We recruited 38 people with PD and 16 healthy controls who walked for 2 min under single- and dual-task conditions while wearing mobile eye-tracking glasses (Tobii Pro Glasses 2, 100 Hz). Pupil response outcomes (velocity, size, difference between eyes) were extracted alongside gait characteristics from inertial sensors. Known groups validity compared PD and controls; convergent/divergent validity examined relationships with cognitive, visual, clinical, and gait measures. Results: People with PD had significantly altered pupil constriction/dilation velocity (p = 0.01), a larger difference between their left and right pupils (p = 0.04), and a larger mean and minimum pupil size (p ≤ 0.01) compared to controls during walking. Pupil response correlated with cognitive function (JLO, CLOX1, TMTB), visual acuity, disease severity (MDS-UPDRS-III), and gait characteristics in both groups. No dual-task effects were observed. Conclusions: Pupil response during walking demonstrates known groups and convergent validity, indicating potential as a clinical biomarker for PD. Following this initial study, more research is required to further validate pupil response in PD (e.g., analytical validation and testing within real-world ecologically valid environments). Full article

Background/Objectives: Rigidity has been defined as an increase in muscle tone that is independent of the velocity of the stretch in Parkinson’s disease (PD). However, there is an ongoing debate about this non-velocity-dependent nature of rigidity in PD. To investigate the behaviour of axial muscle tone at different examination velocities using isokinetic dynamometry, and to determine whether trunk muscle resistance is velocity-dependent in people with PD compared with healthy controls (HCs). Methods: A cross-sectional study was conducted with HC and people with PD (I–III stages of Hoehn and Yahr and assessed by the UPDRS, Section III: motor aspects) by a senior neurologist. The trunk extension–flexion component of an isokinetic dynamometer measured axial muscle tone over a range of 50° (S: 30-50-80). The continuous passive mode with three angular speeds (30°/s, 45°/s and 60°/s) was used to assess muscle tone. Peak torque (N), work (J) and work recorded in the first and in the last third of the explored trunk range of motion were calculated (J) were registered. All these outcomes were performed within 1–3 h of the administration of anti-Parkinsonian medication (ON phase) in the PD sample. Results: People with PD (N = 36) and healthy controls (N = 20) completed the study. Our results showed largely similar behaviour in work and peak torque registered in both groups, by which, resistance measures, like peak torque, weakly increased with mobilisation speed from 30°/s to 45°/s, without reaching statistical significance, but increased from 45°/s to 60°/s, only in the flexors. No clear increase was observed in the work. Furthermore, greater torque measures in PD than controls were only observed for peak torque at 30°/s. Conclusions: Peak torque of trunk flexors–extensors tends to increase as the angular speed increases in both PD and controls. This may suggest that the (relatively slow) tested speeds were likely evaluating the non-neural component of muscle tone. This has implications for the clinical assessment of axial rigidity in PD. Full article

Background/Objectives: Advanced age in Parkinson’s disease (PD) is linked to worse motor function, more severe symptoms, and impaired activities of daily living (ADLs). Lee Silverman Voice Treatment (LSVT)^® BIG may be suitable for older patients, as it can be adapted to individual abilities. This study evaluated whether age affects the effectiveness of LSVT^® BIG on gait speed, motor symptoms, ADLs, and quality of life (QoL) in PD. Methods: In this retrospective, single-center cohort study, 22 patients with PD were divided into an older group (≥65 years; n = 16) and a younger group (<65 years; n = 6). All participants completed 16 one-hour, face-to-face LSVT^® BIG sessions. Gait speed was assessed with the 10-m walk test; motor symptoms with Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III; ADLs with MDS-UPDRS Part II; and QoL with the Parkinson’s Disease Questionnaire-39 Summary Index. Two-way mixed-design analysis of variance with aligned rank transformation was used for statistical analysis. Results: Significant improvements were observed for all outcomes (gait speed, motor symptoms, ADLs, and QoL) after the intervention. A significant effect of age group was found for gait speed, with younger patients walking faster overall. No significant interaction between timepoint and group was observed for any measure. Conclusions: LSVT^® BIG appears to improve gait speed, motor symptoms, ADLs, and QoL in patients with PD, regardless of age, suggesting it is an effective intervention for both older and younger patients. Full article

Background and purpose: Balance and gait problems pose a significant burden in Parkinson’s disease (PD), and they are often poorly treated with levodopa. We intended to summarize evidence of mid- and long-term impact of various physiotherapeutic interventions (≥3 months post-intervention) on dynamic balance, gait, and general motor function in patients with PD. Method: A systematic search was conducted across the PubMed, Cochrane Library, and Scopus databases to identify controlled clinical trials on sustained effects of various exercise interventions in PD on the outcomes of interest (lasting ≥ 3 months after completion of the exercise program). We conducted meta-analyses on commonly used clinical measures of dynamic balance and gait ability, as well as on UPDRS-III scores using the Comprehensive Meta-Analysis Software (CMA). Results: A total of 26 studies were included in meta-analyses, with a total of 1261 participants in the experimental and 989 participants in the control groups. Positive cumulative effects at the post-exercise follow-up (3 to 23 months) were shown in favor of the intervention group regarding balance (SMD = 0.512, 95% CI [0.240, 0.785], p < 0.001, I² = 87%), gait (SMD = 0.614, 95% CI [0.301, 0.926], p < 0.001, I² = 75%), and general motor function (SMD = 0.922, 95% CI [0.559, 1.285], p < 0.001, I² = 87%). Heterogeneity among studies was high for all three outcomes, apparently reflecting diversity with regard to patient characteristics, type, and duration of intervention, as well as the method of outcome assessment. The certainty of evidence was consequently judged as ‘’low’’ to ‘’moderate,’’ according to the GRADE system. Subgroup analyses revealed that balance can sustainably improve mostly through multimodal rather than targeted balance-oriented exercise but also through dual-task exercise, tai chi, and Pilates. Gait showed improvement at follow-up mainly through multimodal exercise, aerobic exercise, dual-task exercise, and Pilates, with benefits confined to early- and mid-stage disease. Sustained UPDRS-III improvement could be achieved through multimodal exercise, which showed a large overall effect but also through aerobic, resistance, and dual-task training, tai chi and qigong. Conclusions: Exercise interventions can improve balance and gait, as well as preserve the overall motor function in patients with PD, also in the mid- and long-term post-intervention periods. Full article

Introduction: Malnutrition and sarcopenia are commonly observed in African patients with Parkinson’s disease (PD); however, limited data exist regarding the nutritional status and body composition of PD patients in sub-Saharan Africa. This study aims to describe the clinical, nutritional, and anthropometric characteristics of PD patients from Sogakope, in the Volta Region of Ghana. Methods: A total of 20 PD patients were recruited. All participants underwent comprehensive clinical and nutritional assessments. Motor symptoms were evaluated with the Unified Parkinson’s Disease Rating Scale (UPDRS). Dealing with non-motor symptoms, constipation was diagnosed according to the Roma III Criteria while dysphagia was assessed using the Swallowing Disturbance Questionnaire. The presence and impact of sialorrhea was determined using the Sialorrhea Clinical Scale. Nutritional assessment was performed with the Mini Nutritional Assessment short form (MNA-sf). Body composition parameters were measured using Bioelectrical Impedance Analysis (BIA), and muscle strength was evaluated with the Handgrip Strength Test. Correlations were assessed by Pearson or Spearman correlation analysis, as appropriate. Partial correlation analysis controlling for significant clinical variables was also performed. Results: Daily caloric intake was significantly lower compared to Western populations and was associated with a reduced body mass index (BMI) and body fat percentage. Constipation (80%) and sarcopenia (45%) were highly prevalent, whereas dysphagia was reported in only 15% of participants. Over 75% of patients were at risk of malnutrition. A significant inverse correlation was found between thigh circumference and disease duration (r = −0.517; p = 0.02). Additionally, protein intake (g/kg/day) was inversely correlated with motor symptom severity, as measured by the UPDRS Part III in the ON state (r = −0.544; p = 0.02). Conclusions: This study demonstrates a high prevalence of nutritional deficiencies, sarcopenia, and altered body composition in Ghanaian PD patients. These nutritional impairments are significantly associated with disease duration and motor symptom severity. The findings highlight the urgent need for early nutritional screening and intervention as part of a multidisciplinary approach to Parkinson’s disease management in resource-limited settings. Full article

Background: Parkinson’s disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, accompanied by neuromelanin loss. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) enables in vivo visualization of these changes; however, its diagnostic and clinical utility remains incompletely defined. This study evaluated the feasibility, reliability, and biological sensitivity of semi-automated NM-MRI–based substantia nigra volumetry in PD. Methods: In this prospective case–control study, 50 participants (25 PD patients and 25 healthy controls) underwent 3T NM-sensitive MRI using a high-resolution T1-weighted spin-echo sequence. Semi-automated segmentation of hyperintense substantia nigra regions was performed using Mango v3.5.1, with intracranial volume normalization derived from FreeSurfer v7.3. Four participants were excluded due to motion artifacts, yielding a final cohort of 46 subjects. Clinical assessment included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III and Hoehn and Yahr (H&Y) staging. Group comparisons, receiver operating characteristic (ROC) analysis, and reliability testing using intraclass correlation coefficients (ICC) were performed. Results: Corrected substantia nigra volume was significantly reduced in PD patients compared with controls (18% reduction; p = 0.039, Mann–Whitney U test). Semi-automated measurements demonstrated excellent agreement with manual segmentation (ICC = 0.945). ROC analysis showed moderate discriminative performance for corrected volume (AUC = 0.700; sensitivity 68.4%, specificity 74.1%). No significant correlation was observed between corrected substantia nigra volume and UPDRS-III motor scores, while a trend toward lower SNc volume was observed with advancing H&Y stage. Conclusions: Semi-automated NM-MRI volumetry detects biologically meaningful substantia nigra volume loss in early-stage Parkinson’s disease with high measurement reliability. However, diagnostic performance was moderate and insufficient for standalone clinical diagnosis or motor severity prediction. These findings support the role of NM-MRI as a complementary imaging marker within multimodal diagnostic and research frameworks rather than as an independent diagnostic tool. Full article

Background: This paper presents a systematic review and meta-analysis to identify the effects of Rhythmic Auditory Stimulation (RAS) delivered via wearable devices on the gait and balance in patients with Parkinson’s disease. Method: The PICO criteria were established according to the PRISMA 2020 guidelines, and literature searches were performed across five databases covering studies published between 2015 and 2025: PubMed, Embase, Cochrane, Scopus, and Web of Science. After applying the inclusion criteria, eleven randomized controlled trials (RCTs) were selected. The quality of the studies was evaluated using the PEDro Scale and ROB-2. Statistical analyses were performed using Review Manager 5.4 based on the number of samples, means, and standard deviations to calculate the effect sizes. Result: The analysis results showed that wearable RAS significantly improved the gait speed (SMD = 0.49, p < 0.05) and balance ability (SMD = 0.40, p < 0.05), while no significant differences in the gait pattern, FOG-Q, or UPDRS-III were observed. The heterogeneity among studies was low, and the funnel plots were distributed symmetrically, indicating minimal publication bias. The average PEDro score was 7.33, suggesting moderate-to-high methodological quality. Conclusion: wearable RAS was identified as an evidence-based intervention effective in improving the gait speed and balance in patients with Parkinson’s disease. Full article

The accurate prediction of motor progression in Parkinson’s disease (PD) remains a major clinical challenge that limits personalized treatment planning and efficient clinical trial design. In this study, we developed and validated a machine-learning framework integrating a targeted panel of plasma proteins measured by Olink proximity extension assays with clinical variables to stratify patients according to their progression risk. We analyzed baseline plasma samples from 211 early-stage PD patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) cohort using four targeted Olink panels, from which 28 circulating proteins were retained after quality-control filtering. Patients were classified as rapid or slow progressors based on their annualized change in MDS-UPDRS Part III scores. Among the algorithms tested, Random Forest achieved the highest discriminative performance with an area under the receiver operating characteristic curve (AUC) of 0.751 (95% CI: 0.684–0.811), which exceeded that of clinical predictors alone (AUC 0.666). The integration of targeted proteomic and clinical features further improved model performance (AUC 0.773; p = 0.009). Nested cross-validation confirmed minimal optimistic bias (AUC 0.743). To enhance clinical interpretability, we applied SHapley Additive exPlanations (SHAP) analysis, which identified interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor A (VEGF-A) as the most influential predictors. SHAP feature rankings were highly stable across cross-validation folds (mean Spearman ρ = 0.91). The robustness of these findings was confirmed through sensitivity analyses using extreme quartile comparisons (AUC 0.823), treatment-naïve subgroup analysis (AUC 0.738), and a clinically anchored outcome definition based on the minimal clinically important difference (AUC 0.739). A decision curve analysis demonstrated a net clinical benefit across threshold probabilities of 0.25–0.70. Our results establish targeted plasma protein profiling combined with interpretable machine learning as a promising tool for PD motor progression risk stratification, with potential applications in individualized patient counseling regarding motor prognosis and the selection of candidates for disease-modifying trials. Full article

The clinical evaluation of motor impairment in Parkinson’s disease is commonly based on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, which relies on visual assessment and is therefore subject to inter-rater variability. Existing technology-based solutions often require wearable sensors or lack structural alignment with the item-based architecture of the clinical examination. This study presents a fully automated and contactless framework designed to quantitatively describe motor performance in tasks explicitly aligned with MDS-UPDRS Part III. The system integrates stereo vision, deep learning-based pose estimation, and acoustic analysis to derive continuous, standardized quantitative descriptors. Objective Motor Item Indices were defined for 17 of the 18 motor items, excluding rigidity, which cannot be inferred from vision-based measurements. The framework was evaluated in a cohort of healthy subjects to establish an internal reference baseline for feature normalization and index construction. Within this cohort, descriptors exhibited coherent multivariate organization and internally consistent distributions, supporting methodological feasibility at this baseline definition stage. This work represents a methodological and baseline definition phase. Clinical validation in Parkinsonian populations, correlation with neurologist-rated scores, and longitudinal assessment remain necessary to determine diagnostic, severity-related, or early-stage applicability. Full article

Introduction: Psychotic symptoms (PS) in Alzheimer’s disease (AD) are associated with unfavorable prognosis, including accelerated functional decline and reduced survival. Multiple neurotransmitter systems have been implicated in the pathophysiology of PS, with the serotonergic system emerging as particularly relevant. Materials and Methods: Between 2010 and 2020, 120 patients with prodromal AD and 26 cognitively healthy controls underwent comprehensive evaluation, including clinical history, neurological and neuropsychological assessment, neuroimaging, and lumbar puncture. All participants underwent longitudinal clinical monitoring for a minimum of five years or until the emergence of PS. In February 2024, baseline cerebrospinal fluid (CSF) serotonin (5-HT) concentrations were quantified using competitive ELISA (FineTest, Wuhan, China). Results: CSF 5-HT levels were significantly elevated (p < 0.003) in patients who subsequently developed psychosis (n = 49) compared with those who remained free of PS during the 8-year follow-up (n = 19). A threshold of 4.89 ng/mL yielded 80% sensitivity for identifying individuals at risk. Baseline Neuropsychiatric Inventory (NPI; p < 0.001) and Unified Parkinson’s Disease Rating Scale part III (UPDRS III; p < 0.009) scores also demonstrated strong discriminative capacity. Conclusions: Measurement of CSF 5-HT and detailed clinical profiling in prodromal AD may provide predictive value for psychosis onset within 8 years of diagnosis. To our knowledge, this is the first study to report CSF 5-HT findings in AD patients. Full article

Background: Placebo effects are well documented in Parkinson’s disease (PD) clinical trials and represent a major methodological challenge in interpreting neuromodulation studies. Although sham stimulation has been associated with clinical improvement, the magnitude, durability, and outcome specificity of placebo-related effects across non-invasive neuromodulation trials remain incompletely characterized. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD1272381). PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library were searched from inception through September 2025. Randomized, sham-controlled trials of non-invasive neuromodulation in adults with PD were included. Results: Seventeen randomized sham-controlled trials (n = 654 participants) involving repetitive transcranial magnetic stimulation and transcranial direct current stimulation were included. Sham stimulation was associated with small but statistically significant improvements in UPDRS Part III (motor examination) at post-intervention and follow-up, whereas no significant placebo-related improvement was observed for UPDRS Total score. Placebo effects were modest and did not increase over time. In contrast, active neuromodulation produced larger and more durable improvements in both UPDRS Total and Part III, with statistically significant effects maintained at follow-up. Conclusions: Placebo effects contribute to short-term clinical improvement in non-invasive neuromodulation trials for PD, particularly for motor examination outcomes, but do not fully account for the sustained benefits observed with active stimulation. Placebo responsiveness is outcome- and time-dependent, underscoring the importance of rigorous trial design, including careful outcome selection, assessment timing, expectancy management, and comparator structures, to accurately estimate neuromodulation efficacy and support clinical translation. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms. The home-based wearable sensor monitoring Parkinson’s KinetiGraph (PKG) evaluates clinical efficacy, caregiver satisfaction, and cost-effectiveness in the clinical management of Parkinson’s disease (PD) compared to prior usual standard care. Methods: We analyzed 50 patients with Parkinson’s disease, comparing baseline clinical outcomes, healthcare utilization, and caregiver burden without PKG to follow-up data after 12 months with PKG. We used IBM SPSS Statistics for the analysis. Statistical significance was set at p < 0.05 for hypothesis testing. We employed the Wilcoxon signed-rank test to evaluate differences between the two time points, while exploratory bivariate associations between caregiver burden (Zarit score) and various outcomes were examined using Spearman’s rank correlation. Results: Over a 12-month period following the implementation of PKG-guided care, significant improvements were observed in various clinical, functional, and economic areas for the patients. Key findings include the following: motor function improved, with UPDRS Part III scores showing a 20% median reduction (from 25 to 20); medication adjustments decreased by 40% (from 5 to 3); outpatient visits were reduced by 60% (from 5 to 2); hospital admissions decreased by 100% (from 1 to 0); caregiver burden, as measured using the Zarit caregiver burden score, declined by 37.5% (from 48 to 30); and total direct medical costs decreased by 17.9% (from AED 261,800 to AED 215,000). Conclusions: These findings indicate substantial reductions in healthcare utilization, costs, and caregiver burden following the integration of PKG monitoring into clinical practice. Full article

Background: In Parkinson’s disease (PD), a higher prevalence of polyneuropathy (PNP) is increasingly recognized, although the causal association is still under debate. In contrast, PNP in atypical parkinsonian syndromes (APS) has been insufficiently addressed, despite preliminary evidence suggesting elevated prevalence. Methods: Nerve conduction studies were performed on 13 patients with multiple system atrophy (MSA) and 9 patients with progressive supranuclear palsy (PSP) at baseline. PNP was diagnosed according to standard electrophysiological criteria after exclusion of common secondary causes. Comprehensive clinical evaluation included motor and non-motor assessments over two years of follow-up. Results: At baseline, PNP was present in 53.8% of MSA patients and 66.7% of PSP patients. MSA patients with PNP showed greater motor symptom severity (UPDRS III score; p = 0.046) and worse cognitive performance (MoCA; p = 0.044) compared to those without PNP. Over two years, a significant reduction in the tibial nerve amplitude was observed exclusively in MSA patients (p = 0.039), paralleling disease progression. Conclusions: This study provides the first longitudinal evaluation of clinical and electrophysiological PNP progression in MSA and PSP. A high comorbidity of PNP in patients with APS could contribute to motor and sensory impairments in these patients. Our findings indicate that PNP progression may reflect disease progression in MSA. Given the limited sample size, larger-scale longitudinal studies are needed to further investigate biomarker potential of PNP in APS and to clarify differences in peripheral nerve involvement between synucleinopathies and tauopathies. Full article