Research on the pathophysiology of Parkinson’s disease (PD) has traditionally been performed with functional magnetic resonance imaging (fMRI); however, only a few studies have been conducted 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 to track the disease progression of PD. This review focuses on the potential application of multimodal longitudinal functional approaches based on the current evidence for the purpose of understanding disease progression and monitoring future therapeutic interventions.
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.
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.
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Summary of the best evidence for non-pharmaceutical interventions for mild cognitive impairment in Parkinson’s disease Yud Dan Liu, Hui Fang Li, Ya Xian Zhai, Yun Xia Shen, Jinmei Yang, Li Mei He, Ting Shen Frontiers in Neurology.2025;[Epub] CrossRef
Objective People with Parkinson’s disease (PwPD) experience a gradual decline in bed mobility independence as the disease progresses. Identifying factors associated with nonindependence in daytime bed mobility is crucial for developing effective interventions to increase independence. We investigated factors associated with nonindependence in daytime bed mobility in PwPD.
Methods This cross-sectional study included 109 PwPD (Hoehn and Yahr [HY] stage 2–4). Patients’ bed mobility ability (turning in bed, supine-to-sitting, and sitting-to-supine) was assessed during the daytime, and they were categorized into independent and nonindependent groups. Potential factors associated with bed mobility independence, 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, were evaluated.
Results The nonindependent group presented 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 revealed that axial symptoms, upper limb rigidity, and trunk extension strength were highly discriminative for nonindependence in turning in bed (the area under the curve [AUC]=0.84). Similarly, upper limb rigidity and axial symptoms were predictive of nonindependence in supine-to-sitting and sitting-to-supine movements (AUC=0.78, 0.92). A significant difference in axial symptoms between the HY stage 4 subgroups was observed only in the sitting-to-supine movement.
Conclusion Our findings indicate that axial symptoms and upper limb rigidity are key factors contributing to nonindependence in daytime bed mobility tasks among PwPD. Targeting these factors in rehabilitation may help mitigate the decline in bed mobility independence in PwPD.
Objective Delayed ON is a condition in which Parkinson’s disease (PD) patients do not experience the effect of levodopa in time after taking the dosage. The ability of various oral levodopa regimens to overcome this problem has been poorly investigated. To evaluate the efficacy of levodopa/benserazide dispersible tablets in PD patients with delayed ON to the first morning dose.
Methods This multicenter, randomized, crossover trial involved 40 eligible PD patients with delayed ON. The participants were randomized to receive either levodopa/benserazide 100 mg dispersible or regular tablets for 4 weeks, followed by a one-week wash-out interval and an alternate drug for another 4 weeks. Participants took the investigational drug with the first morning dose of their antiparkinsonian medications. Other medications were not changed during the trial. The primary outcome was changes in time-to-ON after the first-morning dose recorded in a special diary before and after each therapy. We also evaluated changes in parkinsonism, motor fluctuations, and dyskinesia using the Unified PD Rating Scale and the Unified Dyskinesia Rating Scale. Finally, we investigated whether efficacy was affected by Helicobacter pylori status via baseline serum samples from every participant.
Results Nine patients dropped out during the trial. The time-to-ON was significantly reduced by the dispersible tablet compared with the regular tablet (-34.72 vs. -23.81 minutes, p=0.014). There were no significant changes in parkinsonian severity or dyskinesia with either drug. The dispersible formulation was beneficial for both Helicobacter pylori-positive and -negative groups.
Conclusion Levodopa/benserazide dispersible formulations can improve time-to-ON without exacerbating dyskinesia in PD patients suffering from delayed ON.
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 Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine disorder characterized by a variety of endocrine and neurological manifestations, including extrapyramidal symptoms and intellectual disability.
Methods This report presents the genetic characterization of five Iranian patients with WSS, including the first Iranian patient to undergo deep brain stimulation (DBS).
Results We highlight five Iranian patients with mutations in the DCAF17 gene presenting with variable features of WSS, with symptom onset in early adolescence. Whole exome sequencing identified four homozygous variants (c.436delC, c.982-2A>G, c.580C>T, and c.838+1G>A) within the DCAF17 gene in the probands. Patients had variable responses to common therapies, and one patient achieved significant improvement following DBS.
Conclusion We expand the clinical and genetic heterogeneity among Iranian patients and suggest the c.436delC variant as a founder mutation in the region. We highlight the importance of considering WSS in patients with both neurological and endocrine symptoms and suggest DBS as a potential treatment option.
Objective To evaluate the efficacy of istradefylline in Parkinson’s disease patients experiencing 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 40 mg/day) versus placebo.
Results Data from 2,719 patients, 56% of whom presented with baseline dyskinesia, were analyzed post hoc. The presence of baseline dyskinesia did not affect the mean decrease in “OFF” time with dyskinesia, increase in “ON” time without troublesome dyskinesia, or improvement in the Unified Parkinson’s Disease Rating Scale motor score associated with istradefylline treatment. Dyskinesia was reported in 17% of patients receiving istradefylline, with higher rates for women (21%), patients with a BMI <18.5 kg/m2 (22%), and patients receiving catechol-o-methyltransferase inhibitors plus dopamine agonists (22%) and monoamine oxidase B inhibitors (25%).
Conclusion Istradefylline treatment resulted in greater reductions in total “OFF” hours/day and increases in “ON” time without troublesome dyskinesia than did placebo, regardless of the presence or absence of preexisting dyskinesia.
Expert Commentary on “A Case Report of Palatal Tremor in Progressive Supranuclear Palsy” Shen-Yang Lim, Anthony E. Lang Parkinsonism & Related Disorders.2025; : 107873. CrossRef