Journal of Parkinson's disease最新文献

Complementary and alternative therapies (CAT) is an umbrella term applied to a diverse set of approaches, with high interest among persons with Parkinson's disease. However, scientific community regards evidence-based medicine as the only acceptable, creating a black and white dichotomy, which is neither epistemologically correct nor workable in daily practice. CAT are heterogeneous, and the label is dynamic as new scientific insights might accrue. Medicine encompasses a wide range of interventions that can be positioned alongside a spectrum of credibility, with many shades of grey between the extremes. We define credibility along three dimensions: the underlying rationale, the scientific rigor, and patient perceptions. By no means this implies we encourage adoption of weakly grounded therapies, or favor exotic treatments over evidence-based approaches. Credibility serves as basis for a nuanced debate in clinical practice, with attention to adverse effects, interactions, and costs. The degree of credibility also informs the need for further research. This offers a practical road forward for open-minded, yet rational decisions by persons with Parkinson's disease, clinicians, funding bodies and relevant stakeholders.

BackgroundParkinson's disease (PD) is a common neurodegenerative disease lacking treatments that modify progressive neuron loss. Terazosin (TZ) increases activity of the glycolytic enzyme phosphoglycerate kinase 1 and could potentially benefit impaired brain bioenergetics in PD. Preclinical data are encouraging, but we lack human data on relationships between TZ dose and measures of TZ target engagement in women and men.ObjectiveThis study evaluated the dose-dependent effects of TZ on brain and systemic bioenergetics and safety and tolerability in neurologically healthy older adults.MethodsWe administered TZ (1, 5, and 10 mg/day) to 18 neurologically healthy 60-85-year-old people. We measured plasma and cerebrospinal fluid TZ concentrations and changes in levels of whole blood ATP, brain ATP with ³¹P magnetic resonance spectroscopy, cerebral metabolic activity with ¹⁸F-FDG PET imaging, and plasma metabolomics. We also assayed tolerability and safety.ResultsTZ crossed the blood-brain barrier, and 5 mg/day increased whole blood ATP and decreased brain ¹⁸F-FDG uptake. TZ 1 mg/day lacked significant effects, and 10 mg/day did not produce additional metabolic benefit compared to 5 mg/day. These effects were similar for both sexes. Mild dizziness occurred in 3 females and 1 male.ConclusionsThese findings in humans align with results from preclinical cell, animal, and epidemiological studies. Our data show that TZ increases markers of energy metabolism with a biphasic dose-response and suggest that 5 mg/day TZ may provide maximal benefit while minimizing adverse consequences of higher doses. These results lay groundwork for clinical trials in people with PD.

Previous studies have shown differences in the microbiota of patients with Parkinson's disease (PD) compared to healthy controls (HC). To deduce a possible causality, it is highly relevant to examine changes in the prodromal phase. This study investigated the microbiome in stool samples of individuals with isolated REM sleep behavior disorder (iRBD, n = 32) compared to clinical PD (n = 23) and HC (n = 34) and showed significant changes of beta-diversity in PD and iRBD patients compared to HC (p = 0.025; p = 0.003), with an increase in proinflammatory species in iRBD and PD and decrease in SCFA-producing bacteria in PD.

BackgroundMitochondrial dysfunction, particularly complex I (CI) deficiency, is considered an integral feature of Parkinson's disease (PD). However, recent findings indicate that widespread neuronal CI deficiency in the brain is only present in a subpopulation of 20-30% of cases. This stratification may be relevant for selecting participants for clinical trials, emphasizing the need for clinically applicable biomarkers. We previously reported CI deficiency in skeletal muscle biopsies of a subpopulation of persons with PD (PwPs), suggesting potential for mitochondrial stratification using extra-neural tissues. Platelets are another tissue previously reported to exhibit mitochondrial respiratory defects in PD. However, studies have generally involved small sample sizes and reported variable results.ObjectiveTo determine whether platelets exhibit impaired mitochondrial respiratory chain complex activity in PwPs, or in a subpopulation of PwPs.MethodsUsing spectrophotometric activity assays, we assessed CI and complex IV (CIV) activities in platelet samples from 61 PwPs and 31 neurologically healthy controls from a well-characterized prospective cohort. The correlation between activities measured in platelets and skeletal muscle was also explored in 51 of the same individuals.ResultsPlatelet CI and CIV activities showed no difference between PwPs and controls at the group level, nor evidence of a subgroup with deficiency of either complex. There was no correlation between complex activities in platelet samples and skeletal muscle biopsies from the same individuals.ConclusionsBased on these results, we propose that platelet CI or CIV activities are not sensitive markers of mitochondrial dysfunction in PD.

Parkinson's disease (PD) is marked by motor symptoms and often accompanied by mild cognitive impairment (PD-MCI), affecting up to 50% of patients and preceding PD dementia (PDD). Genetic factors may influence this progression, yet the underlying mechanisms remain unclear. This study investigated genetic factors influencing the progression from PD-MCI to PDD using polygenic risk scores (PRS). A genome-wide association study (GWAS) was conducted using data from the LANDSCAPE study. Multivariable Cox regression, Kaplan-Meier survival analysis, and concordance statistics assessed the relationship between PRS and PDD progression. No significant association was found between PD PRS and the risk of developing PDD.

BackgroundThis study presents post-hoc analyses of the LEAP study focusing on disease progression in patients with early Parkinson's disease (PD) who either have a glucocerebrosidase gene (GBA1) mutation (GBA1mut) or do not have a mutation (GBA1wt) over a period of up to five years.ObjectiveTo investigate the difference in disease progression between GBA1mut and GBA1wt over 80 weeks and five years.MethodsThe study analyzed the difference in disease progression between GBA1mut and GBA1wt using the UPDRS and its subscales, Levy A and B scores, and the difference in levodopa equivalent daily dose (LEDD) over 80 weeks and five years, with mixed-effects regression models.ResultsThe GBA1 mutation carrier status was determined in 394 patients, with 52 being GBA1mut and 342 being GBA1wt. From baseline to 80 weeks, the change in total UPDRS score was similar for GBA1mut and GBA1wt (difference 1.7 points in favor of GBA1mut, p = 0.38). From baseline to five years, GBA1mut had 5.9 points (p = 0.04) more worsening of total UPDRS compared to GBA1wt and GBA1mut had 1.0 point (p = 0.02) more deterioration in UPDRS subscale IV, related to therapy complications, compared to GBA1wt. There were no significant between-group differences in changes in UPDRS subscales, Levy A and B scores, and LEDD.ConclusionsThese findings suggest that over the long term, PD patients with a GBA1 mutation experience faster disease progression compared to those without a GBA1 mutation, although this difference in progression was not apparent within the initial 80 weeks of the trial.

BackgroundAtypical parkinsonian syndromes are highly prevalent in the French West Indies (FWI), making up 70% of degenerative parkinsonisms and including "Caribbean Atypical Parkinsonism". Environmental neurotoxins from Annonaceae plants are implicated. Despite close ties, parkinsonism data for French Guiana remain limited.ObjectiveThis study aimed to compare atypical parkinsonism frequencies between French Guiana and FWI, assess clinical characteristics in French Guiana, and evaluate potential environmental toxin exposure.MethodsDegenerative parkinsonism patients were recruited from a community-based population in French Guiana and compared with a FWI cohort.ResultsAmong 372 patients (67 from French Guiana, 305 from FWI), atypical parkinsonian syndromes accounted for 41.8% in French Guiana, lower than in FWI (66.2%, p < 0.001). In French Guiana, these syndromes were more common in males (sex-ratio: 3 vs. 1.22 in FWI, p = 0.044; adjusted p-value = 0.281) and often involved cerebellar symptoms (p < 0.001). Cases not fitting classical subtypes were classified as "other atypical parkinsonian syndromes" (35.7% in French Guiana, 41.6% in FWI), with a supranuclear palsy-like phenotype often presenting with additional rapid eye movement (REM) sleep behavior disorder, hallucinations, or orthostatic hypotension. Annonaceae consumption was higher in FWI (93%) than in French Guiana (79.2%, p < 0.001), while alcohol use was more common in French Guiana (p = 0.005).ConclusionsAtypical parkinsonism in French Guiana resembles that in FWI but is less common, with an intermediate prevalence between Caucasian and Caribbean populations. Shared environmental factors, such as Annonaceae exposure, may contribute to this presentation, supporting the term "Caribbean Atypical Parkinsonism" for both regions.

BackgroundThe association between body mass index (BMI), metabolic conditions, and incident Parkinson's disease (PD) is quite complex.ObjectiveTo investigate the relationship between these variables, particularly the impact of metabolically healthy overweight/obese on the risk of PD, in the general population.MethodsA total of 402,059 participants from the UK Biobank were categorized into four phenotypes according to the presence of overweight/obesity and/or metabolically abnormal status: overweight/obesity was defined as BMI ≥25 kg/m²; metabolically abnormal status was defined as having one or more metabolic risk factors including elevated blood pressure, fasting glucose, or triglyceride level, or reduced high-density lipoprotein cholesterol level. Cox proportional hazard regression analyses using four different models were performed to compare the risk of developing PD among the four BMI-metabolic status phenotypes.ResultsDuring the median follow-up of 13.5 years, 2283 (0.6%) patients were newly diagnosed with PD. Cox regression models demonstrated that individuals with overweight/obesity and those with metabolic abnormalities were at a higher risk of developing PD than their counterparts. Compared with the metabolically healthy non-overweight group (reference group), the two metabolically abnormal groups (either overweight/obese or non-overweight) showed a higher incidence of PD. The metabolically healthy overweight/obese group exhibited a comparable risk of developing PD to the metabolically healthy non-overweight group.ConclusionsThis study demonstrated that metabolically abnormal conditions are more relevant to incident PD than overweight/obesity. In particular, a metabolically healthy overweight/obese status does not increase the risk of developing PD compared with a metabolically healthy non-overweight status.

BackgroundSleep disturbances are prevalent and debilitating non-motor symptoms in patients with Parkinson's disease (PD).ObjectiveThis study aimed to explore sleep architecture and the prevalence of polysomnographic (PSG) sleep findings in PD, examining the associations between sleep parameters and other clinical characteristics.MethodsThe study included 97 PD patients (age: 67.1 ± 7.9) and 42 non-PD controls (age: 64.7 ± 9.7). Participants underwent clinical assessment and video-PSG. Sleep parameters, apnea-hypopnea index (AHI), periodic limb movements index (PLMI), and REM sleep without atonia (RSWA) were obtained. General linear models were used to explore interactions between disease duration and sleep variables in predicting PD symptoms.ResultsNearly 94% of PD patients showed at least one video-PSG-assessed sleep finding, including AHI-defined obstructive sleep apnea (OSA), periodic limb movements, and RSWA. Sleep alterations correlated with disease severity, with reduced sleep duration and efficiency, higher sleep latency, and higher AHI being associated with worse PD severity. Sleep efficiency was more strongly associated with motor symptoms and disease severity at longer disease duration, while AHI exhibited a stronger relationship with motor symptoms at shorter disease duration. Finally, PD patients showed significant alterations in sleep macrostructure compared to controls, including reduced sleep duration (d = 0.75) and efficiency (d = 1.15) and decreased percentage of stage 3 non-REM sleep (d = 0.37).ConclusionsThe study showed a high prevalence of video-PSG-defined sleep findings in PD, with interactions between disease duration, sleep efficiency, and AHI. The present results support personalized management of sleep disturbances in PD to potentially improve symptoms and reduce the burden of illness.