Journal of Parkinson's disease最新文献

Background: Preclinical evidence suggests calcineurin inhibitors (CNIs) combat α-synuclein-induced neuronal dysfunction and motor impairments. However, whether CNIs prevent or treat Parkinson's disease (PD) in humans has never been investigated.

Objective: We seek to ascertain if prescription of CNIs is linked to a decreased prevalence of PD in a varied patient population and to glimpse into the mechanism(s) and target site through which CNIs might decrease PD prevalence.

Methods: We analyzed electronic health records (EHRs) from patients prescribed the brain penetrant CNI tacrolimus (TAC), the peripherally restricted CNI cyclosporine (CySp), or the non-CNI sirolimus (SIR). For comparison, EHRs from a diverse population from the same network served as a general population-like control. After propensity-score matching, prevalence, odds, and hazards of PD diagnoses among these cohorts were compared.

Results: Patients prescribed CNIs have decreased odds of PD diagnosis compared to the general population-like control, while patients prescribed SIR do not. Notably, patients prescribed TAC have a decreased prevalence of PD compared to patients prescribed SIR or CySp.

Conclusions: Our results suggest CNIs, especially those acting within the brain, may prevent PD. The reduced prevalence of PD in patients prescribed TAC, compared to patients prescribed SIR, suggests that mechanisms of calcineurin inhibition- other than immunosuppression, which is common to both drugs- are driving the reduction. Therefore, CNIs may provide a promising therapeutic approach for PD.

Pregnancy in women with early-onset Parkinson's disease (PD) is likely to have a higher frequency given the trend toward increasing maternal age, thus resulting in a greater overlap time between childbearing age and PD risk. Deep brain stimulation (DBS) therapy is nowadays offered to PD patients at earlier stage of the disease, when women can still be pre-menopausal. However, few data are available about DBS safety during pregnancy. From a review of the available literature, only one article was published on this topic so far. Therefore, we have developed a clinical consensus on the safety of DBS during pregnancy in PD patients.

Background: Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion.

Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies.

Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking.

Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038).

Conclusions: Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Orthostatic hypotension (OH) is the most common manifestation of cardiovascular autonomic dysfunction in Parkinson's disease. In this viewpoint, we discuss five practical questions regarding OH in Parkinson's disease: 1) How common is the problem? 2) Why should people with Parkinson's disease and providers care about OH? 3) What are the symptoms of OH? 4) How to confirm a diagnosis of OH? And 5) How to treat OH? OH is an important non-motor symptom of Parkinson's disease for which we have available treatments to significantly mitigate morbidity and possibly positively impact the disease course.

In the UK, guidance exists to aid clinicians and patients deciding when treatment for Parkinson's disease (PD) should be initiated and which therapies to consider. National Institute for Health and Care Excellence (NICE) guidance recommends that before starting PD treatment clinicians should discuss the following: the patient's individual clinical circumstances; lifestyle; preferences; needs and goals; as well as the potential benefits and harms of the different drug classes. Individualization of medicines and management in PD significantly improves patients' outcomes and quality of life. This article aims to provide simple and practical guidance to help clinicians address common, but often overlooked, co-morbidities. A multi-disciplinary group of PD experts discussed areas where clinical care can be improved by addressing commonly found co-morbidities in people with Parkinson's (PwP) based on clinical experience and existing literature, in a roundtable meeting organized and funded by Bial Pharma UK Ltd. The experts identified four core areas (bone health, cardiovascular risk, anticholinergic burden, and sleep quality) that, if further standardized may improve treatment outcomes for PwP patients. Focusing on anticholinergic burden, cardiac risk, sleep, and bone health could offer a significant contribution to personalizing regimes for PwP and improving overall patient outcomes. Within this opinion-based paper, the experts offer a list of guiding factors to help practitioners in the management of PwP.

Parkinson's disease (PD) unfolds with pathological processes and neurodegeneration well before the emergence of noticeable motor symptoms, providing a window for early identification. The extended prodromal phase allows the use of risk stratification measures and prodromal markers to pinpoint individuals likely to develop PD. Importantly, a growing body of evidence emphasizes the heterogeneity within prodromal and clinically diagnosed PD. The disease likely comprises distinct subtypes exhibiting diverse clinical manifestations, pathophysiological mechanisms, and patterns of α-synuclein progression in the central and peripheral nervous systems. There is a pressing need to refine the definition and early identification of these prodromal subtypes. This requires a comprehensive strategy that integrates genetic, pathological, imaging, and multi-omics markers, alongside careful observation of subtle motor and non-motor symptoms. Such multi-dimensional classification of early PD subtypes will improve our understanding of underlying disease pathophysiology, improve predictions of clinical endpoints, progression trajectory and medication response, contribute to drug discovery and personalized medicine by identifying subtype-specific disease mechanisms, and facilitate drug trials by reducing confounding effects of heterogeneity. Here we explore different subtyping methodologies in prodromal and clinical PD, focusing on clinical, imaging, genetic and molecular subtyping approaches. We also emphasize the need for refined, theoretical a priori disease models. These will be prerequisite to understanding the biological underpinnings of biological subtypes, which have been defined by large scale data-driven approaches and multi-omics fingerprints.

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: 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.