Journal of Parkinson's disease最新文献

Background: Stigma is a relevant aspect of Parkinson's disease (PD). Specific stigma tools are needed to address the complex construct of stigma in PD comprehensively.

Objective: To test the dimensionality and psychometric properties of the newly developed Parkinson's Disease Stigma Questionnaire (PDStigmaQuest).

Methods: In this multi-center, cross-sectional study including PD patients and healthy controls, the dimensionality of the PDStigmaQuest was examined through exploratory factor analysis. Acceptability and psychometric properties were investigated. PDStigmaQuest scores of patients and healthy controls were compared.

Results: In total, 201 PD patients and 101 healthy controls were included in the final analysis. Results suggested high data quality of the PDStigmaQuest (0.0001% missing data for patients). The exploratory factor analysis produced four factors: felt stigma, hiding, enacted stigma: rejection, and enacted stigma: patronization, explaining 47.9% of variance. An optional work domain for employed patients was included. Moderate floor effects and skewness, but no ceiling effects were found. Cronbach's alpha of 0.85 indicated high internal consistency. Calculated item-total correlations met standard criteria. Test-retest reliability was high (rs = 0.83). PDStigmaQuest scores correlated significantly with other stigma measures (rs = 0.56-0.69) and were significantly higher in patients than in healthy controls and higher in patients with depressive symptoms than in those without.

Conclusions: The patient-reported 18-item PDStigmaQuest showed strong psychometric properties of validity and reliability. Our results suggest that the PDStigmaQuest can be used to assess and evaluate stigma comprehensively in PD, which will improve our understanding of the construct of PD stigma.

 Inflammation and immune dysregulation have been linked to the pathogenesis and progression of Parkinson's disease (PD), and represent an attractive target for therapeutic intervention, given the potential for repurposing of existing anti-inflammatory and immunomodulatory agents. Despite the fact that initial studies of drugs with secondary anti-inflammatory effects did not yield positive results, agents specifically targeting immune and inflammatory pathways may hold more promise. This article will briefly review the evidence base for targeting the immune system and neuroinflammation in PD, and discuss in detail the recently completed and currently active trials of primary anti-inflammatory/immunomodulatory drugs in PD.

Increasing evidence suggests a potential role for infectious pathogens in the etiology of synucleinopathies, a group of age-related neurodegenerative disorders including Parkinson's disease (PD), multiple system atrophy and dementia with Lewy bodies. In this review, we discuss the link between infections and synucleinopathies from a historical perspective, present emerging evidence that supports this link, and address current research challenges with a focus on neuroinflammation. Infectious pathogens can elicit a neuroinflammatory response and modulate genetic risk in PD and related synucleinopathies. The mechanisms of how infections might be linked with synucleinopathies as well as the overlap between the immune cellular pathways affected by virulent pathogens and disease-related genetic risk factors are discussed. Here, an important role for α-synuclein in the immune response against infections is emerging. Critical methodological and knowledge gaps are addressed, and we provide new future perspectives on how to address these gaps. Understanding how infections and neuroinflammation influence synucleinopathies will be essential for the development of early diagnostic tools and novel therapies.

Background: Whether body weight changes are associated with Parkinson's disease (PD) mortality remains uncertain.

Objective: To investigate the association between changes in body mass index (BMI) and all-cause mortality in patients with PD.

Methods: This nationwide cohort study enrolled 20,703 individuals with new-onset PD (ICD-10 code: G20 and a rare intractable disease registration code: V124) who underwent health screening program by the Korean National Health Insurance Service within two years from pre- and post-PD diagnosis. We identified nine BMI change groups based on three BMI status: underweight (BMI <  18.5 kg/m2), normal or overweight (18.5 kg/m2≤BMI <  25 kg/m2), and obese (BMI≥25 kg/m2).

Results: Of 20,703 individuals, 3,789 (18.0%) died during the follow-up period. Excessive weight loss to underweight in the obese group (hazard ratio [HR] = 3.36, 95% CI:1.60-7.08), weight loss in the normal to overweight group (HR = 2.04, 95% CI:1.75-2.39), sustained underweight status (HR = 2.05, 95% CI:1.67-2.52), and weight gain from underweight to normal or overweight (HR = 1.52, 95% CI:1.15-2.02) were associated with increased mortality. Sustained obese status (HR = 0.80, 95% CI:0.74-0.87) and weight gain in the normal to overweight group (HR = 0.82, 95% CI:0.71-0.95) were associated with reduced mortality.

Conclusions: We found that BMI change at diagnosis was associated with mortality in patients with PD. Specifically, being underweight either before or after diagnosis as well as experiencing weight loss, were associated with increased mortality. These findings provide valuable insights for weight management planning in PD, highlighting the importance of individualized approach that consider pre-diagnosis BMI.

Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has emerged as a potent treatment for alleviating motor symptoms in Parkinson's disease (PD). Despite its effectiveness, the impact of high frequency STN-DBS on cerebellar oscillations remains unclear, posing an intriguing challenge for neural modulation. Given the direct and indirect connections between the STN and cerebellum, we investigated whether STN-DBS affects cerebellar oscillations.

Objective: To observe the effects of STN-DBS on cerebellar oscillations in patients with PD.

Methods: We recruited 15 PD patients receiving STN-DBS. Electroencephalographic (EEG) signals were recorded from cerebellar regions during resting-state conditions in both the OFF-DBS and STN-DBS conditions. Our analyses centered on spectral features, particularly theta and beta oscillations, guided by prior research and correlation tests to investigate the relationship between oscillatory changes and motor symptom severity.

Results: In the mid-cerebellar (Cbz) region, we observed a significant increase in the relative power in all frequency bands, including theta and beta oscillations during STN-DBS, showing the global effect of DBS. Importantly, the correlation results indicated significant associations between mid-cerebellar (Cbz) beta power during the OFF condition and motor severity, which were not evident during STN-DBS. Interestingly, correlations between beta power and motor severity were not observed at the mid-occipital (Oz) and mid-frontal (Cz) regions. Notably, signal similarity analyses demonstrated no evidence of volume conduction effects between the mid-cerebellar (Cbz) and nearby mid-occipital (Oz) regions.

Conclusions: While these findings provide valuable insights into the complex interplay between STN-DBS and neural oscillations, further research is essential to decipher their precise functional significance and clinical implications. Understanding these intricacies may contribute to the optimization of DBS therapies for PD.

Background: Pain fluctuations are a characteristic phenomenon in advanced Parkinson's disease (PD), but their temporal association with motor and non-motor symptom (NMS) fluctuations remains largely enigmatic. Moreover, data on their importance for disease severity perception and health-related quality-of-life (hr-QoL) is limited.

Objective: To dissect pain fluctuations with respect to pain type and frequency patterns, and their association with motor and non-motor fluctuations.

Methods: Prospective observational cohort study in advanced PD assessing symptom fluctuations by simultaneous hourly ratings using the PD Home diary (Off, On, Dyskinetic state), a pain diary (assessing 9 pain types) and a non-motor diary (10 key NMS) based on validated instruments.

Results: Forty-seven out of 55 eligible participants with fluctuating PD (51% men, median age 65, median disease duration 10 years) had sufficient datasets (>95% of hours) from 2 consecutive days. Pain was reported in 35% of waking hours with clear circadian rhythm peaking in early morning Off periods and clustering during motor Off state (49% of Off state hours with pain). Main NMS co-fluctuating with pain were "Fatigue" and "Inner Restlessness". Simultaneous assessment of global disease severity by participants revealed that pain was associated with worse disease severity only in motor On and Dyskinetic state but not in Off state, which translated into significant correlations of daily pain times with hr-QoL only during motor On and Dyskinetic state.

Conclusions: Aside from treating motor Off periods, specific recognition of pain particularly during motor On and Dyskinetic state comprises an important aspect for disease management in advanced PD.

Background: Enhancing the interactions between study participants, clinicians, and investigators is imperative for advancing Parkinson's disease (PD) research. The Canadian Open Parkinson Network (C-OPN) stands as a nationwide endeavor, connecting the PD community with ten accredited universities and movement disorders research centers spanning, at the time of this analysis, British Columbia, Alberta, Ontario, and Quebec.

Objective: Our aim is to showcase C-OPN as a paradigm for bolstering national collaboration to accelerate PD research and to provide an initial overview of already collected data sets.

Methods: The C-OPN database comprises de-identified data concerning demographics, symptoms and signs, treatment approaches, and standardized assessments. Additionally, it collects venous blood-derived biomaterials, such as for analyses of DNA, peripheral blood mononuclear cells (PBMC), and serum. Accessible to researchers, C-OPN resources are available through web-based data management systems for multi-center studies, including REDCap.

Results: As of November 2023, the C-OPN had enrolled 1,505 PD participants. The male-to-female ratio was 1.77:1, with 83% (n = 1098) residing in urban areas and 82% (n = 1084) having pursued post-secondary education. The average age at diagnosis was 60.2±10.3 years. Herein, our analysis of the C-OPN PD cohort encompasses environmental factors, motor and non-motor symptoms, disease management, and regional differences among provinces. As of April 2024, 32 research projects have utilized C-OPN resources.

Conclusions: C-OPN represents a national platform promoting multidisciplinary and multisite research that focuses on PD to promote innovation, exploration of care models, and collaboration among Canadian scientists.