Journal of Parkinson's disease最新文献

BackgroundFreezing of gait (FoG) is a debilitating symptom in Parkinson's disease (PD), yet its pathophysiological mechanisms remain poorly understood. Several studies have investigated the FoG neuroimaging correlates, with heterogeneous results.ObjectiveThis study investigated in a large PD cohort whether the disparate neuroimaging findings may converge to a common brain network.MethodsT1-weighted MRI scans of 500 PD patients (90 with FoG [PD-FoG] and 410 without FoG [PD-nFoG]) were acquired from the Parkinson's Progression Markers Initiative. A voxel-based morphometry (VBM) analysis was conducted to identify clusters of decreased grey matter (GM) in PD-FoG patients. Subsequently, VBM coordinates of significant clusters were used as seed regions to generate connectivity network maps using a large functional normative connectome, and these maps were overlapped to identify regions connected with most VBM clusters.ResultsPD-FoG patients showed GM atrophy in cerebellar lobes, hippocampus, putamen, insula, inferior temporal gyrus and lateral orbitofrontal gyrus compared with PD-nFoG patients. Network analysis revealed that these regions colocalized within a specific brain network focused on midbrain, substantia nigra, subthalamic nucleus, globus pallidus, inferior putamen and dorsal medial cerebellum. These findings were confirmed by using coordinates from previous VBM studies for the network analysis, validating our results.ConclusionsThis study revealed a brain network underlying FoG in PD, reducing the heterogeneity of previous neuroimaging evidence on FoG. These results may represent a significant step forward in the understanding of FoG and may be relevant for optimized targeted neuro-modulatory treatments to reduce FoG in PD patients.

BackgroundParkinson's disease (PD) patients on dopaminergic drugs may experience non-motor fluctuations (NMFs) which are often heterogeneous and respond variably to treatments.ObjectiveWe evaluated if personality was associated to NMFs and could modulate the NMFs responsiveness to dopaminergic medication and deep brain stimulation of the sub-thalamic nucleus (STN-DBS).MethodsFrom the PREDISTIM cohort, personality dimensions of 235 PD patients were assessed by the Temperament and Character Inventory (TCI) before STN-DBS (V0). NMFs were evaluated using the NMFs Severity Scale at V0 and one year after STN-DBS (V1). Linear regression models were performed between TCI dimensions and NMFs at V0; and logistic regression models were done between TCI dimensions and 1) groups of dopa-sensitive patients (responders to ON medication at V0) versus non-dopa-sensitive ones, and 2) responders versus non-responders to STN-DBS at V1. Odds ratios (OR) were also calculated.ResultsSignificant associations were found between two TCI personality dimensions ("Harm Avoidance" and "Self-Directedness") and severity of NMFs in OFF medication at V0: PD patients with higher Harm Avoidance and lower Self-Directedness scores having more NMFs. TCI personality dimensions were not associated with the dopa-sensitivity while Novelty Seeking was significantly associated with the STN-DBS-responder group for the psychiatric (OR = 1.09 [1.02-1.17]) and for the dysautonomic NMFs (OR = 1.11 [1.04-1.18]).ConclusionsCertain personality dimensions (Harm Avoidance and Self-Directedness) are associated with NMFs severity at baseline, and PD patients with high Novelty Seeking seem to be better candidates for NMFs improvement after STN-DBS.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene associate with familial and sporadic Parkinson's disease (PD). While various LRRK2 allelic variants have been studied, characteristics of R1441C carriers remain underexplored. We compared PD patients carrying the R1441C mutation (90% Israeli Arabs) to those carrying the G2019S (70% Ashkenazi Jews) and R1441G (42% Basque) variants. R1441C carriers exhibited a distinct clinical phenotype characterized by severe motor and non-motor symptoms and worse scores on the Montreal Cognitive Assessment. These findings highlight the importance of ethnic diversity and genetic stratification in PD research. These results need confirmation in larger, more diverse samples.

People from Black backgrounds are underrepresented in Parkinson's research, despite evidence of higher disease burden and risk of dementia. Greater understanding of the factors influencing participation in Parkinson's research can improve recruitment, quality and generalizability of both observational research studies and clinical trials. Through focus groups with 17 people with Parkinson's and carers from Black communities, we identified distrust in the research process, stigma of Parkinson's diagnosis, and accessibility as key barriers to research participation. Participants made recommendations including: raising awareness of Parkinson's and related research, involving community ambassadors, improving communication throughout the research process, and providing practical support.

Alpha-synuclein is a normal protein, but misfolded forms in the cerebrospinal fluid can be detected using the alpha-synuclein seed amplification assay (αSyn-SAA), a potential biomarker for Parkinson's disease (PD). Some experts consider this assay a 'game changer' for redefining and reclassifying PD. In this article, we, three individuals with PD, share our perspective on the suitability of αSyn-SAA as the basis for a new classification and staging system for PD. We also discuss other biomarkers and their relevance to those with PD, drawing on our research and the scientific background of two authors. We aim to clarify complex media reports and study findings for the PD community. We argue that while αSyn-SAA can identify the presence of pathology, it cannot explain the underlying cause for such pathology or predict the progression of PD. Given the varied biological pathways leading to PD, using αSyn-SAA as a unified biological definition for a new classification system is premature. Further research is needed before it can serve as the foundation for defining and staging Parkinson's disease. Although αSyn-SAA has its place, like the DAT scan, it should be seen as a tool for confirming diagnoses rather than defining them.

BackgroundParkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. While abnormal protein aggregation has been classically implicated in PD, increasing evidence suggests that lipid dysregulation may also contribute to neuronal vulnerability. Recent studies have begun to link abnormal phosphatidylserine (PS) metabolism to mitochondrial impairment and dopaminergic neuron loss in PD, yet the underlying cellular mechanisms remain poorly defined.ObjectiveThis study aimed to determine how impaired PS synthesis in cortex glia affects mitochondrial function, oxidative stress, and dopaminergic neuron survival, using a Drosophila model of glia-specific Phosphatidylserine synthase (Pss) knockdown.MethodsTo dissect the glial contribution to PS-related neurodegeneration, we employed a Drosophila model in which the Pss gene was selectively knocked down in cortex glia using the GAL4-UAS system. We evaluated PD-like phenotypes by assessing the number of dopaminergic neurons in the PPL1 and PPL2 clusters, as well as locomotor activity and lifespan, following glia-specific knockdown of Pss gene.ResultsCortex glia-specific knockdown of Pss impaired locomotion and reduced lifespan in flies, indicating a systemic decline in neuronal and mitochondrial function. Pss knockdown reduced mitochondrial transcription factor A (Tfam) expression, disrupted mitochondrial gene expression, and elevated ROS levels. Western blot analysis also revealed reduced AKT phosphorylation without changes in total AKT. These results ultimately lead to loss of dopaminergic neurons.ConclusionsThese findings establish a mechanistic link among abnormal PS metabolism, impaired AKT signaling, mitochondrial dysfunction, and dopaminergic neuron loss. Our study provides novel evidence that glia-driven abnormalities in PS metabolism may cause PD-like neurodegeneration, offering mechanistic insights and potential therapeutic targets.

Gender differences in progressive supranuclear palsy (PSP) may become relevant for clinical trials, treatment decisions and patient counseling. To study gender associated differences we conducted a retrospective data analysis of 191 male and 157 female PSP patients from a large multicenter observational cohort in Germany. While no differences in motor skills, disease severity, daily living abilities, global cognitive status and depressive symptoms were observed between genders, male patients showed significantly higher apathy scores, a finding also noted in other neurological diseases. In this study, apart from male patients exhibiting higher levels of apathy, no significant disease-specific gender differences were observed in PSP patients.

BackgroundMultiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia, and autonomic dysfunction. Putaminal hypointensities on T2 magnetic resonance imaging (MRI) are commonly observed in the parkinsonian variant of MSA (MSA-P).ObjectiveTo report a neuropathologically confirmed case of MSA-P with an atypical MRI presentation, characterized by progressive T2 hyperintensity in the putamen, without significant iron accumulation.MethodsWe present the clinical course, imaging findings, and neuropathological results of a 57-year-old woman with MSA-P. Diagnostic evaluations included serial brain MRI, cerebrospinal fluid analysis, magnetic resonance spectroscopy, and post-mortem pathological examination.ResultsThe patient initially presented with L-dopa-responsive bradykinesia and right-dominant rigidity, followed by progressive motor decline, orthostatic hypotension, and urinary retention. Serial T2-weighted MRI revealed diffuse and progressively increasing hyperintensity in the putamen, accompanied by atrophy predominantly on the left side. Autopsy confirmed the diagnosis of MSA, revealing severe neuronal loss, marked gliosis, and abundant glial cytoplasmic inclusions in the putamen, with only mild iron deposition as shown by Prussian blue staining.ConclusionsThis case demonstrates that severe putaminal neurodegeneration in advanced MSA can be associated with progressive T2 hyperintensity on MRI, reflected by the absence of substantial iron deposition. These findings indicate that iron-independent mechanisms contribute to the pathophysiology of MSA-related putaminal damage in patients with MSA.

BackgroundDepression can negatively influence an individual's perception of their disease. Although subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), some patients do not appreciate benefits despite showing objective improvements in motor function.ObjectiveWe explored the impact of depressive symptoms on self-reported outcomes of PD severity in patients who underwent STN-DBS.MethodsAssessments took place preoperatively and 2-years after surgery. Patients completed the Hospital Anxiety and Depression Scale (HADS), Unified Parkinson's Disease Rating Scale (UPDRS) Parts 2 and 4, Gait and Falls Questionnaire, Parkinson's Disease Questionnaire-39 (PDQ-39), and the Non-motor Symptoms Scale. The UPDRS Part 3 (motor examination) was also performed. Patients were dichotomized into two groups (normal or high) based on their postoperative follow-up HADS depression score.ResultsEighteen patients (33.3%) were assigned to the high group (hHADS-D), and 36 patients (66.7%) were assigned to the normal group (nHADS-D). The UPDRS Part 3 OFF-medication score improved to a similar extent in both groups, and participants experienced a similar reduction in their levodopa equivalent daily dose following STN-DBS. Unlike the nHADS-D group, however, hHADS-D patients did not self-report improvements on any clinical outcome measure at follow-up from baseline, and instead indicated a significant worsening on the UPDRS Part 2 ON-medication and PDQ-39 cognition domain. This was not explicable by their preoperative non-motor symptom burden, nor changes in dopaminergic medications. There were no differences between groups in terms of proportion using anti-depressants, surgical complications or postoperative side effects.ConclusionsDepressive symptoms may play a significant role in subjective self-reporting, and should be carefully considered when evaluating STN-DBS effectiveness and managing patients postoperatively.

BackgroundCompensation strategies have been shown to improve functional mobility in people with Parkinson's disease (PD) who live independently. However, knowledge on its utilization in in long-term care (LTC) settings is unknown.ObjectiveThis study aimed to establish the knowledge and utilization of compensation strategies for functional mobility for individuals with PD among healthcare professionals working in LTC facilities in the Netherlands. Secondary aims included assessing subgroup differences among healthcare professionals and exploring perceived barriers to utilizing these strategies in LTC.MethodsA cross-sectional online survey design was conducted with (allied) healthcare professionals working in LTC facilities across the Netherlands.ResultsOverall knowledge and utilization of compensation strategies among 130 healthcare professionals was high, with a median of 5 out of 7 known categories, 4 out of 7 used for gait, and 3 out of 5 for transfers. Variations among professions existed, with physiotherapists and occupational therapists demonstrating higher scores than nurses and personal care assistants. Professionals specifically trained in PD care and those working in specialized PD departments demonstrated a higher level of knowledge. Main identified barriers for utilization were limited knowledge and time of the healthcare professionals, and concerns regarding limited feasibility in patients with severe cognitive impairments.ConclusionsWhile knowledge and utilization of compensation strategies for PD in LTC facilities was widespread, the findings highlight a need for tailored training programs for healthcare professionals to improve patient care. Future research should evaluate the feasibility and usefulness of such training programs.