Journal of Movement Disorders最新文献

Background: Continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) represents a transformative therapy for advanced Parkinson's disease (aPD), but real-world neuropsychiatric safety data remain limited, particularly in populations typically excluded from trials. Objective: To assess the frequency, clinical patterns, and predictors of neuropsychiatric and/or cognitive worsening in a real-world CSFLI-treated cohort.

Methods: We performed a retrospective observational study of 36 consecutive aPD patients initiating CSFLI with six-month follow-up. Neuropsychiatric/cognitive worsening was defined as any clinically meaningful increase in MDS-UPDRS Part I or PDQ-8 cognitive/psychiatric subscores. Patients were classified as "worsening" versus "no worsening" and compared for baseline characteristics. Predictors were identified using univariable and exploratory multivariable analyses.

Results: Seventeen patients (47.2%) experienced neuropsychiatric/cognitive worsening within six months. Critically, patients with prior confusion or hallucinations who were managed with baseline clozapine had significantly better outcomes: confusion history 57.9% in stable group versus 11.8% in worsening group (p=0.006); clozapine use 63.2% versus 23.5% (p=0.023). Conversely, COMT inhibitor (COMT-I) use was more frequent in the worsening group (70.6% vs 21.1%, p=0.006). Motor outcomes remained stable at 6 months regardless of neuropsychiatric status.

Conclusions: In a vulnerable real-world aPD population, neuropsychiatric/cognitive worsening under CSFLI was more frequent than in pivotal trials (47% vs 7-17%) but generally mild and without motor deterioration. Importantly, proactive clozapine use enabled safe CSFLI treatment in patients with psychiatric histories traditionally considered high-risk. COMT-I emerged as a modifiable risk factor. Findings support broader CSFLI use with structured neuropsychiatric monitoring and proactive clozapine in selected patients.

Objective: In late-stage Parkinson's disease (PD), wheelchair mobility becomes essential, yet little is known about endurance and efficiency. For individuals who struggle with manual wheelchair (MW) propulsion, a cycling wheelchair (CW) may provide an alternative. This study compared endurance and efficiency between MW and CW during continuous driving, including turning tasks in late-stage PD.

Methods: Nine participants with late-stage PD performed the 6-Minute Push Test using both MW and CW. Total distance, average speed, and the Physiological Cost Index (PCI) were measured. PCI was calculated from pre- and post-driving heart rates.

Results: CW resulted in significantly greater total distance and lower PCI than MW, and similar patterns were observed in participants at Hoehn and Yahr stage V (n = 6).

Conclusion: CW use may enable more enduring and efficient mobility than MW use in late-stage PD. Further studies are needed to validate these preliminary findings.

Objective: Impact of statin use on progression and survival in Parkinson's disease (PD) remains unclear; limited evidence in Asian populations. This study aims to assess association between statin prescription, cumulative dosage, and all-cause mortality in PD.

Methods: This retrospective cohort study was conducted using a population-based sample from the Korean National Health Insurance Service (KNHIS) claims database. The study included 3,152 adults diagnosed with PD, with history of statin use and cumulative dose information obtained from claims records. Data were collected from the KNHIS database, and all eligible participants were followed longitudinally to ascertain all-cause mortality. The primary outcome was all-cause mortality, and the exposures were statin use (yes or no) and cumulative dose. The analysis was conducted using Cox proportional hazards regression, adjusted for relevant covariates.

Results: Statin use associated with lower all-cause mortality risk (hazard ratio [HR], 0.600; 95% CI, 0.521-0.691). Among statin users, higher cumulative statin dose linked to further mortality reduction (HR, 0.800; 95% CI, 0.761-0.842).

Conclusions: Statin use and higher cumulative exposure were associated with reduced all-cause mortality in patients with Parkinson's disease, and these findings suggest a potential survival benefit and warrant further investigation in diverse populations.

Background: Brain-derived neurotrophic factor (BDNF) has been suggested to support dopaminergic neuron's endurance and dopamine release. Its Val66Met polymorphism might modify Parkinson's disease (PD) evolution, although evidence in Asian populations remains limited. This study aimed to explore how the BDNF rs6265 genotypes are associated with the clinical characteristics and longitudinal progression patterns of PD patients in a Korean population.

Methods: A total of 247 patients were enrolled and followed for a mean duration of 50.9 ± 23.9 months. Baseline and/or periodic assessments captured motor severity, non-motor burden, cognition, orthostatic stress, cardiac denervation, and presynaptic dopamine transporter availability. The repeated measures were manipulated to infer any genotypic differences in the trajectories of each clinical domain.

Results: Genotype frequencies were 31.2% (77/247) for Val/Val and 68.8% (170/247) for Met-allele carriers. Baseline clinical characteristics and presynaptic dopamine transporter availability were comparable between genotypes; however, Val homozygotes showed more preserved myocardial innervation and poorer non-frontal cognitive performance. Longitudinal analyses demonstrated genotype-specific increases in motor and cognitive severity. Compared to Met-allele carriers, the homozygous Val group exhibited accelerated motor progression and more rapid decline in frontal domain after three years of follow-up.

Conclusions: The differences in myocardial denervation at diagnosis, cognitive profiles, and motor progression might suggest a potential modulatory role of BDNF polymorphism in PD progression in the Korean population.

Objective: This study aims to investigate the clinical relevance of occipital hypoperfusion in patients with Parkinson's disease (PD) with respect to clinical phenotype and the risk of dementia conversion.

Methods: We enrolled 349 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET). Patients with PD were classified into three groups based on posterior cortical perfusion patterns on early-phase 18F-FP-CIT PET images: PD with preserved posterior cortical perfusion (n=186), PD with parieto-temporal hypoperfusion (n=84), and PD with parieto-temporo-occipital hypoperfusion (n=79). Baseline clinical features and dementia conversion risk were compared across PD groups.

Results: Patients with preserved posterior cortical perfusion were younger than those in the other PD groups. Compared with the other groups, the parieto-temporo-occipital hypoperfusion group tended to have lower Cross-Cultural Smell Identification Test scores, a higher prevalence of rapid eye movement sleep behavior disorder, higher Unified PD Rating Scale motor scores, and more severe reductions in striatal dopamine transporter availability. The risk of dementia conversion was lower in patients with preserved posterior cortical perfusion than in those with posterior cortical hypoperfusion. However, the risk of dementia conversion did not differ between the parieto-temporal and parieto-temporo-occipital hypoperfusion groups.

Conclusion: Additional occipital hypoperfusion was not associated with an imminent risk of dementia conversion in patients with PD with posterior cortical hypoperfusion. Nonetheless, occipital involvement may serve as an indicator of the diffuse malignant subtype of PD.

Objective: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been proposed to be a downstream mediator of neuroinflammation in individuals with Parkinson's disease (PD). However, its involvement across disease stages and related synucleinopathies, such as multiple system atrophy (MSA), remains unclear. We aimed to analyze the peripheral mRNA expression of NLRP3-related genes and cytokines across individuals with isolated REM sleep behavior disorder (iRBD), early-stage PD, late-stage PD, and MSA.

Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 151 participants: 35 healthy controls (HCs), 31 patients with iRBD, 41 patients with early-stage PD, 21 patients with late-stage PD, and 23 patients with MSA. mRNA expression was measured using quantitative real-time polymerase chain reaction. Statistical comparisons were performed using analysis of variance (ANOVA) or Welch's ANOVA, and associations with clinical variables were analyzed through stepwise multiple linear regression.

Results: NLRP3 expression was significantly lower in patients with iRBD (p=0.0263) and patients with early-stage PD (p= 0.0101) than in HCs. NIMA-related kinase 7 (NEK7) expression progressively decreased across the disease spectrum (HCs vs. patients with early-stage PD, p=0.0008; vs. patients with late-stage PD, p<0.0001). In contrast, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 were elevated in patients with PD, especially those in the late stages. Levels of patients with MSA resembled those of HCs but differed from those of patients with PD. Interleukin (IL)-1β and IL-18 levels were not significantly different. In patients with early-stage PD, NLRP3 expression was negatively correlated with disease duration, the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part II score, and the cognitive score.

Conclusion: Our findings challenge the prevailing hypothesis that NLRP3 inflammasome activation directly contributes to PD pathogenesis. Instead, the observed increase in ASC and caspase-1 expression suggests the potential involvement of alternative inflammasome pathways during disease progression.

Objective: Parkinson's disease (PD) affects approximately 2% of individuals over the age of 60. With more than two billion Muslims observing Ramadan, individuals with PD encounter specific challenges, such as deteriorating motor skills, sleep disturbances, and an increased risk of falls during fasting.

Methods: Our study focused on 75 patients with idiopathic PD divided into two groups: the Ramadan Regime group, which consisted of 50 patients whose medication was adjusted to twice daily at Suhoor and Iftar, and the Nontreatment group, which included 25 patients who abstained from medication for religious reasons. Both groups were instructed to wear a Parkinson's KinetiGraph (PKG) wrist device.

Results: The study findings revealed that motor function worsened in the Nontreatment group (p<0.001) but improved in the Ramadan Regime group (p=0.007). Daytime sleepiness also significantly increased in the Nontreatment group (p<0.001).

Conclusion: Overall, the findings suggest that the Ramadan regime significantly enhances patient health and quality of life.