The study of pathophysiology of Parkinson´s disease (PD) has been traditionally performed with functional magnetic resonance imaging (fMRI), however only a few studies have been set in longitudinal cohorts. In the present literature review, we aim to summarize the most recent progress in functional fMRI studies in prospective cohorts and more specifically in combination with other biomarkers, in order to track the disease progression of PD. This review focusses in the potential application of the multimodal longitudinal functional approaches based in the current evidence for the purpose to understand disease progression and monitoring future therapeutic interventions.
Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging and promising technology for treating movement disorders, such as essential tremor and tremor-dominant Parkinson’s disease. It utilises advanced ultrasound transducer emitters to condense sound waves at a precisely defined point able to target various brain areas, such as the pallidothalamic tract, thalamus, and pallidum that ameliorates some of the symptoms of Parkinson’s disease and other movement disorders like dystonic and action induced tremors. we review the current status of preclinical and clinical trials clinical use, treatment outcomes and indications of Magnetic resonance-guided focused ultrasound (MRgFUS)
Introduction Exercises have been proposed as adjuvants for the treatment of Parkinson's disease (PD); however, responses to exercise interventions have shown inconsistent results. We investigated clinical factors associated with improvements in motor deficits after exercise.
Methods 85 PD patients were enrolled from five tertiary hospitals and classified into four exercise groups: home exercises, strength training, Tai Chi, and yoga. Clinical measurements of the motor and non-motor features of PD were assessed at baseline and 12 weeks after the exercise intervention. We employed principal component analysis (PCA) to reduce variables into ten factors and then examined associations of baseline characteristics with percentage improvement in the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) using the Bayesian regression model.
Results In the multivariate Bayesian regression model including ten PCA-driven factors, the percentage improvement of the MDS-UPDRS III was associated with factors including prominent motor deficits (posterior interval; mean ± SD, – 3.9 ± 1.7) and non-motor symptoms such as depression, anxiety, and subjective memory impairment (2.5 ± 1.5). Another factor related to functional impairments in gait and postural control was associated with less improvement after the exercise intervention (3.3 ± 1.7). In the subgroup analyses, motor features were associated with improvement in the home exercise and strength training groups, whereas mood disturbance, fatigue, and subjective cognitive impairment were related to changes in the home exercise and Tai Chi groups.
Conclusions Our results suggest that individual phenotypes of PD patients may be associated with clinical improvement following exercise.
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.
Objective Exercise is a critical nonpharmacological 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 function in patients with PD.
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 Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and timed up-and-go (TUG) test parameters. The assessed secondary outcomes included physical activity (measured via short physical performance battery and the 6-minute walking test [6MWT]), balance (measured via the Mini-BEST), and freezing of gait (measured via the New Freezing of Gait Questionnaire).
Results Home exercise and tai chi demonstrated significant improvements in the MDS-UPDRS Part III scores over 24 weeks. The 6MWT was improved by home exercises and tai chi; additionally, the Mini-BEST test scores were enhanced by strength exercises and yoga. The total duration and forward movement of the TUG test, as well as the turning duration measured via the wearable sensor, were markedly improved in the yoga group.
Conclusion Our results support the notion that various types of adherence to and outcomes of exercise can be observed in real-world settings, even though the effectiveness of exercise is well established. These findings highlight the importance of tailoring exercise regimens by considering individual patients in PD management.
Objective 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 with the LTF angle.
Methods PwP attending outpatient rehabilitation (March 2018–March 2023) were assessed via still images. The PLS direction, its relationship with the LTF angle, and the LTF angle on the PLS side were analyzed.
Results Among 158 patients, PLS was contralateral in 80 (50.6%), ipsilateral in 43 (27.2%), and absent in 35 (22.2%). In the contralateral PLS, but not in the ipsilateral PLS, the PLS angle was correlated with the LTF angle (r=0.48, p<0.001). The LTF angle was greater in the contralateral shift (8.5°±9.6°) than in the ipsilateral shift (2.8°±4.2°, p<0.001).
Conclusion Based on the positive relationship between the LTF angle and contralateral shift angle, evaluation criteria that include PLS are needed for PwP with LTF.
Objective To investigate shoulder function and muscle alterations in patients with Parkinson’s disease (PD) and determine their associations with spinopelvic parameters and clinical status.
Methods This prospective cohort study included 62 PD patients, divided into postural instability and gait difficulty (PIGD) (n=30) and non-PIGD (n=32) groups, as well as 35 controls. The American Shoulder and Elbow Surgeons (ASES) score, shoulder range of motion (ROM), and shoulder muscle stiffness were assessed for each group. Clinical demographics, PD severity, and shoulder-related parameters were extracted and analyzed.
Results Compared with the control group, the PIGD group had significantly lower total and subscored ASESs (all p<0.05). Compared with the controls, both the PIGD and non-PIGD groups demonstrated reduced abduction and forward flexion (all p<0.05). Compared with the non-PIGD group and the control group, the PIGD group also presented decreased external rotation (all p<0.05). Infraspinatus muscle stiffness was greater in the PIGD group than in the control group (p=0.012). Correlation analysis revealed that shoulder condition was significantly associated with PD severity and the PIGD score, whereas muscle stiffness was linked to spinopelvic alignment and the PIGD score. Various clinical factors, including PD severity, the PIGD score, the tremor score, and spinopelvic alignment, were significantly correlated with shoulder ROM.
Conclusion PD patients experience 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.
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Shed Syndecans (1–3), ELA-32, BDNF, NLR, and hs-CRP in Parkinson’s Disease: Appropriate Diagnostic and Prognostic Biomarkers When Combined in a Unique Panel Carmela Rita Balistreri, Daniele Magro, Letizia Scola, Paolo Aridon, Paolo Ragonese, Felipe Augusto Dos Santos Mendes, Giuseppe Schirò, Marco D’Amelio International Journal of Molecular Sciences.2025; 26(10): 4503. CrossRef
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.
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Teneligliptin, a DPP4 Inhibitor Protects Dopaminergic Neurons in PD Models via Inhibiting of Oxidative Stress and Ferroptosis Linting Huang, Jiakai Pi, Liqin Gu, Zirou Liao, Wenya Wang European Journal of Pharmacology.2025; : 177782. CrossRef
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; 12: 100330. CrossRef
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