Journal of Parkinson's disease最新文献

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.

The subtyping of Parkinson's Disease (PD) into brain-first and body-first PD has a powerful neuropathological, neuroimaging and clinical basis, supported by most relevant subsequent studies that have examined its validity. Here, we put forward the idea that the previous classification into early and late onset PD may be related to this categorization. The mean age of motor onset in brain-first PD may be up to 10 years earlier than body-first PD. Early onset PD has features related to brain-first PD, including relative clinical and nigrostriatal neurodegeneration asymmetry and a relatively restricted motor phenotype. In fact, PD as described by James Parkinson, could represent both early onset and brain-first PD, accounting for the famous phrase "senses and intellect uninjured". We suggest here that, at the population level, age of onset could be used as a proxy for brain-first vs body-first PD, notwithstanding the lack of a direct one-to-one correlation and of a clear dichotomy in early vs. late onset PD, which rather represents a continuum. This would enable large scale population studies into the underlying genetic and epidemiological basis of these presumed separate nosological entities. Along these lines, there are some indications of a divergent exposure and genetic basis in early vs. delayed onset PD, and body-first vs. body-first PD respectively. Thus, studies of the etiopathological basis of PD could examine data sets with clinical data limited to age of onset, keeping in mind that within the overall concept of sporadic PD there may be two qualitatively different disease processes.

Sleep problems are among the most frequently reported non-motor symptoms of Parkinson's disease (PD), with a broad range of disorders: insomnia, REM sleep behavior disorder, restless legs syndrome, excessive daytime sleepiness, and sleep-related breathing disorders. These disturbances evolve in complexity across PD severity stages, significantly impact the patients' quality of life and may exacerbate motor and other non-motor symptoms. Neurodegenerative processes, impaired function of neurotransmitters, medication side effects, circadian rhythm dysfunction are among the most proposed mechanisms that may explain the frequent occurrence of sleep disorders in PD. However, there are still many unanswered questions related to the pathophysiological mechanisms of sleep disorders in PD that may offer the clue to better therapeutical options. Although the prevalence of sleep disturbances is very high, the treatment options are still limited. The current review focuses on main sleep disturbances encountered in PD, pathophysiological insights, current therapeutical options and future perspectives for a better and more personalized management of these disorders in PD.

A definitive diagnostic test for Parkinson's disease (PD) remains elusive, so identification of potential biomarkers can facilitate diagnosis and early intervention. Two dogs were trained to distinguish between dry skin swabs obtained from people with Parkinson's (PwP) and control participants. After 38-53 weeks of training on 205 samples, the dogs were tested in a double-blind trial using 60 control and 40 target (drug-naïve PwP) samples. They each showed high sensitivity (70% and 80%) and specificity (90% and 98%). This supports previous findings that dogs can be trained to reliably detect the odor of PD.

BackgroundEarly onset Parkinson's disease (EOPD), defined as Parkinson's disease (PD) diagnosed before age 50, often presents unique challenges compared to late-onset PD, particularly with regard to non-motor symptoms. Psychosis in EOPD is associated with increased functional impairment and may lead to a higher mortality risk.ObjectiveOur study is aimed to determine the prevalence of psychosis in EOPD patients and its impact on all-cause mortality, along with examining the effects of antipsychotic medications and Selective Serotonin Reuptake Inhibitors (SSRIs) on mortality in EOPD patients.MethodsOur retrospective cohort included EOPD patients diagnosed between 1990 and 2022 at Mayo Clinic, Rochester, Minnesota. Psychosis was defined using the National Institute of Neurological Disorders and Stroke/the National Institute of Mental Health (NINDS/NIMH) Work Group criteria. Cox proportional hazards models were used to analyze the association of psychosis and medications with mortality.ResultsOf 829 patients with EOPD, 158 (19.1%) developed psychosis at a median of 12.1 years after PD motor symptom onset. Psychosis was significantly associated with increased mortality in unadjusted (HR = 4.31, 95% CI: 2.59-7.18, p < 0.001) and adjusted (HR = 3.55, 95% CI: 2.10-6.01, p < 0.001) models. No significant difference in mortality risk was observed between patients treated with antipsychotics or SSRIs versus those who were not.ConclusionsPsychosis is a possible complication in EOPD and is associated with a significant increase in all-cause mortality. The use of antipsychotics and SSRIs did not significantly alter the mortality risk in these patients. Further research is needed to understand the mechanisms driving this association and to develop tailored interventions.