Journal of Parkinson's disease最新文献

Exercise is an essential part of the treatment of Parkinson's disease. However, certain symptoms can make exercise difficult. In this viewpoint, we describe an under recognized symptom called running-induced dystonia (RID), which can prevent people with Parkinson's from exercising in their preferred way. We summarize the existing literature and use three case studies to outline potential mechanisms, aggravating and relieving factors and both pharmacological and non-pharmacological therapies to get rid of RID.

BackgroundImpaired gait initiation is a debilitating motor symptom in people with Parkinson's disease (PD). During self-paced (uncued) gait initiation, anticipatory postural adjustments (APAs) are often absent or attenuated, and the first steps are abnormally short. External sensory cues can significantly improve APAs.ObjectiveThe effect of external cueing on lower limb muscle activation during gait initiation, compared to self-initiated steps, was examined in people with PD and healthy older adults (HOA).MethodsGround reaction forces, center of pressure excursions, and lower-limb surface electromyographic profiles (in seven bilateral muscles) were examined in 32 individuals with PD (off-medication) and 10 age-matched HOA during the APA and first step of self-paced or acoustically cued gait initiation.ResultsAnterior (tibialis anterior, vastus lateralis, rectus femoris) and gluteus medius muscles were primarily activated during the early phases of gait initiation, while later phases predominantly involved posterior (soleus, gastrocnemius, biceps femoris) and gluteus medius activations. Cueing facilitated anterior muscles and suppressed posterior muscle activity in both groups, however, activation patterns in PD were not restored to HOA levels. Instead, the PD group had lower early activity during the APA (compared to HOA) and higher late activity.ConclusionsCueing increased anterior muscle activation during gait initiation, rather than evoking a global gain across muscles and timings, demonstrating that cueing predominantly facilitates neural circuitry critical for early APA phases. People with PD showed enhanced late phase activity, probably to compensate for ineffective APAs, and thus have a stronger need to facilitate cue-evoked improvements.

Mancini et al.'s framework for gait assessment in Parkinson's disease (PD) is a valuable contribution, enabling a harmonization of study protocols in this research field and, consequently, a substantial improvement of data interpretation across different cohorts. However, we believe that recommendations concerning data curation and software use should be provided in more detail. To ensure data interoperability and facilitate robust data aggregation from such protocols, appropriate and harmonized data formatting and metadata standards are necessary. We further advocate for the open sharing of gait analysis algorithms, to enhance reproducibility and foster collaborative development.

BackgroundPeripheral neuropathy in Parkinson's disease (PD) may not be an isolated pathological phenomenon but may interact with other non-motor symptoms.ObjectiveTo conduct a comprehensive investigation of the non-motor symptoms observed in PD patients, with a comparative analysis between patients with and without peripheral neuropathy, to explore the relationships between peripheral neuropathy and non-motor symptoms.Methods100 PD patients were recruited from the Neurology Department of Guangdong Provincial People's Hospital. Extensive clinical data were collected, and assessments were performed to evaluate both motor and non-motor symptoms in patients with and without peripheral neuropathy. Spearman's rank correlation analysis was employed to evaluate the association between peripheral neuropathy and non-motor symptoms. Multiple linear regression analysis was conducted to adjust for confounding variables to clarify the impact of peripheral neuropathy on non-motor symptoms.Results57 individuals (57%) were identified as having peripheral neuropathy. Of these, 38 individuals were diagnosed with small fiber neuropathy. After adjusting for confounding variables, higher scores on the 13-item Small Fiber Neuropathy Symptom Inventory Questionnaire were significantly correlated with heightened symptoms of depression (B = 0.498, 95% CI = 0.080-0.917, p = 0.020), anxiety (B = 0.504, 95% CI = 0.099-0.908, p = 0.015), autonomic dysfunction (B = 1.118, 95% CI = 0.828-1.409, p < 0.001), and sleep disturbances (B = 0.694, 95% CI = 0.309-1.080, p = 0.001).ConclusionsPD patients with neuropathy, particularly those with small fiber neuropathy, demonstrate more pronounced non-motor symptoms. The severity of small fiber neuropathy is correlated with the extent of depression, anxiety, autonomic dysfunction, and sleep disturbances. These findings underscore the necessity for routine screening and early detection of peripheral neuropathy in PD patients.

BackgroundType 2 diabetes mellitus (DM) can influence the phenotype and progression of Parkinson's disease (PD), as both conditions share inflammation as a common pathogenic mechanism.ObjectiveTo explore peripheral inflammatory indices that reflect the impact of DM on PD.MethodsWe analyzed 52 drug-naïve PD patients with DM and 182 without DM, along with age- and sex-matched healthy control (HC) with and without DM in a 1:1 ratio. Clinical features were evaluated, including the Hoehn and Yahr (H&Y) scale and the Unified Parkinson's Disease Rating Scale (UPDRS). Peripheral inflammatory markers included the count of leukocyte subpopulations, high-density lipoprotein-cholesterol (HDL-C), and markers derived from these including neutrophil-to-HDL-C ratio (NHR), monocyte-to-HDL-C ratio (MHR), and lymphocyte-to-HDL-C ratio (LHR).ResultsThere were no significant differences in age, sex, or disease duration between PD with DM and PD without DM group. The PD with DM group showed more symmetric motor features (p = 0.007) compared to the PD without DM group. NHR, MHR, and LHR were elevated in the PD with DM group compared to the other groups. Notably, MHR was highest in the PD with DM group, followed by the HC with DM group and the PD without DM group, and HC without DM group (9.73 vs. 8.30 vs. 7.63 vs. 6.46, p < 0.001). MHR positively correlated with clinical scales, including H&Y and UPDRS, across all PD patients (p < 0.05 for all).ConclusionsOur study suggests that MHR effectively reflects the peripheral inflammatory status related to both PD and diabetes.

Diagnosing α-synucleinopathies and assessing target engagement in trials is hindered by the lack of reliable biomarkers. Here, we introduce a first-in-kind quantitative, highly sensitive, and disease-specific diagnostic assay, named Seeding Amplification ImmunoAssay (SAIA), developed and validated to detect synucleinopathy-linked disorders. To this end, we used wide range of specimens, including 38 brain homogenates (BH) and 559 cerebrospinal fluid (CSF) samples from subjects with diverse synucleinopathy disorders, non-synucleinopathy diseases, idiopathic REM sleep behavior disorder (iRBD), and controls. SAIA generated robust results detecting disease-related α-synuclein seeds in BH samples at attogram levels, as referenced to preformed fibrils of α-synuclein. Furthermore, we conducted side-by-side comparisons between SAIA and a traditional Seeding Amplification Assay (SAA), which revealed high concordance. Further, SAIA distinguished synucleinopathies from non-synucleinopathies and controls with sensitivities and specificities ranging between 80-100% and area under the curve values exceeding 0.9. SAIA also accurately identified 24/24 (100%) iRBD cases, considered a prodromal state of PD, with 100% sensitivity and 80% specificity. Further optimization of SAIA through timepoint analyses revealed that shorter incubation times enhanced the assay's specificity for distinguishing MSA from PD highlighting the potential for improved differentiation between specific synucleinopathies. In conclusion, SAIA represents a novel, high-throughput method to screen, diagnose, and monitor synucleinopathy disorders in living subjects, offering significant improvements over existing methods through its quantitative output, shorter incubation time, and simplified workflow, features that enhance its suitability for clinical trial applications.

The Parkinson pandemic continues to spread. Almost 12 million individuals now have the disease, nearly double the estimate from just six years ago. Its human-made nature is also increasingly clear as more studies tie environmental toxicants to the disease. Chief among these are certain pesticides, the dry-cleaning chemicals trichloroethylene and perchloroethylene, and air pollution. An etiological role for these toxicants-inhaled or ingested-is also consistent with the emerging brain- and body-first models of Parkinson's disease.To address the pandemic will require a "PLAN" that (1) Prevents the disease; (2) Learns why it starts; (3) Amplifies the voices of persons with the disease and their caregivers; and (4) Navigates the frontier of new treatments. Reducing or eliminating toxicants will help slow its rise. Learning why the disease begins will require investigating exposures, interactions of the environment with genes, and modifiers. Amplifying the voices of those affected can raise awareness, improve care, and change the disease's course. Vastly expanding the scale and scope of research funding will accelerate efforts to prevent the disease and find more effective therapies. If successfully implemented, such a plan will translate to bold "0-10-100" goals by 2035. The goals include a 0% rise in the global incidence of Parkinson's, a 10-fold increase in research funding and in the proportion devoted toward prevention, and 100% of individuals having access to levodopa and receiving appropriate care. The results will lay the foundation for even greater ambitions, including the fall of Parkinson's disease.

BackgroundGiven the increasing global prevalence of Parkinson's disease (PD) and its complex etiopathogenesis, understanding the role of environmental factors is crucial. Prior investigations suggested a potential link between metal exposure and PD, yet conflicting results emerged.ObjectiveTo identify differences in metal concentrations in whole blood and cerebrospinal fluid (CSF) in PD patients compared to controls.MethodsThe study involved an untreated de novo PD patient cohort from a single-center (n = 102, 38% females, mean age 59.5 (SD 12.5)) and a group of controls with comparable age and sex distribution (n = 127, 35% females, mean age 57.5 (SD 12.4)). Whole blood in all participants and CSF samples in a subgroup (n = 57/55 PD/controls) were collected and concentrations of V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sn, Hg, and Pb, were determined through inductively coupled plasma mass spectrometry.ResultsPD patients exhibited higher concentrations of Hg in both blood and CSF (p = 0.003). Cr concentrations were lower in both blood (p = 0.004) and CSF (p < 0.001) of PD patients. Altered Fe metabolism was evident, with higher blood (p = 0.001) and lower CSF (p = 0.002) Fe concentrations. Other metal alterations in PD included higher Zn (p = 0.008) in blood and lower Co (p < 0.001), Mn (p = 0.006), V (p = 0.009), and Ni (p < 0.001) in CSF.ConclusionsThe findings highlight abnormalities in metal concentrations in biofluids associated with PD, particularly regarding Hg, Cr, and Fe which exhibited alterations in blood and CSF. These findings suggest metal dysregulation in PD, particularly Hg, Cr, and Fe, with potential implications for understanding PD pathogenesis.

BackgroundApathy, defined as a quantitative reduction in goal-directed activity, is a non-motor manifestation that can be present in Parkinson's disease (PD). It seems to be a risk factor for conversion to dementia (PDD) in this population. Amyloid-β deposition also predicts progression to PDD.ObjectiveWe aimed to investigate whether PD patients with apathy showed higher amyloid burden than those without, as well as how these features may influence the rate of progression to dementia.MethodsWe conducted an observational cross-sectional and longitudinal study. Forty-eight PD patients were recruited, including 20 with apathy and 28 without it according to the Starkstein Apathy Scale. They underwent clinical and cognitive evaluations and [¹⁸F]-Flutemetamol PET. The neuropsychological assessment was repeated after 3 years. The predictive value of apathy and amyloid burden for conversion was assessed via logistic regression. Longitudinal trajectories across neuropsychological tests were modeled with linear mixed-effects.ResultsPatients with apathy showed worse performance on several cognitive domains. Using disease duration and global cognition Z-score as covariates, amyloid burden was higher in apathetic vs. non-apathetic patients, mainly in the frontal and temporal cortices. Non-apathetic patients did not have regions with higher amyloid burden in comparison with apathetic patients. After 3 years' follow-up, the conversion rate to worse cognitive state was significantly higher in apathetic (47.4%) vs. non-apathetic (12.0%) patients (p < 0.05). Logistic regression showed that amyloid burden, but not apathy, predicted 3-year cognitive conversion (χ² = 9.95, p < 0.05).ConclusionsApathetic patients exhibit greater amyloid burden and higher cognitive deterioration over time than their non-apathetic counterparts.

BackgroundThe rest-activity rhythm (RAR) captures the distribution of rest and activity periods between and within days. Disturbed RAR has been observed in Parkinson's disease (PD), but the contribution of motor and non-motor symptoms to RAR disturbances remains unclear.ObjectiveTo evaluate the extent to which motor and non-motor symptoms account for variations in RAR between people with PD (PwPD).Methods464 PwPD and 105 age-matched controls of the ProPark cohort underwent assessment of motor, psychiatric, sleep, and autonomic function. Participants wore a wrist motion sensor for one week to measure RAR, i.e., relative amplitude, interdaily stability, and intradaily variability. Associations between RAR, and demographic and clinical variables were examined using backward stepwise regression models.ResultsPwPD had lower relative amplitude (p < 0.001), lower interdaily stability (p < 0.001), and higher intradaily variability (p < 0.001), than healthy controls. Motor impairment (β=-0.262, 95% CI = [-0.487,-0.125], R²=6.8%) and the presence of orthostatic hypotension (OH) (β=-0.142, 95% CI = [-0.276,-0.026], R²=1.9%) were associated with lower relative amplitude. Motor impairment (β=0.129, 95% CI = [0.005,0.238], R²=2.5%), the presence of OH (β=0.182, 95% CI = [0.079,0.307], R²=3.6%), and higher age (β=0.158, 95% CI = [0.039,0.277], R²=4.0%) were associated with higher intradaily variability, while female gender (β=-0.196, 95% CI = [-0.318,-0.088], R²=4.7%) was associated with lower intradaily variability. Female gender was linked to higher interdaily stability (β=0.205, 95% CI = [0.071,0.321], R²=4.2%).ConclusionsMore severe motor impairment and having OH are associated with RAR disturbances in PwPD. Future studies are needed to evaluate whether optimizing treatment of motor impairment and OH, both symptomatic and asymptomatic, can improve RAR and increase mobility for PwPD.