Journal of Parkinson's disease最新文献

BackgroundCare for persons with Parkinson's disease (PD) is to a great extent carried out by care partners. It is important to understand their needs to ease their burden and help with their important role.ObjectiveTo present (1) what is known about needs in caregiving for someone with PD from both qualitative and quantitative papers; and (2) to identify research gaps in the existing literature to guide future research.MethodsA systematic search was conducted, searching PubMed, CINAHL, PsychINFO, and MEDLINE for both qualitative and quantitative studies examining care partner needs in Parkinson's disease published from the start of the databases up to 13 November 2024. The best-fit framework synthesis method was employed for qualitative data extraction and analysis. The Critical Appraisal Skills Programme (CASP) and the Newcastle-Ottawa Scale (NOS) were used for quality assessment of studies.ResultsForty-eight qualitative studies, ten quantitative studies, and three mixed methods studies met the eligibility criteria. All studies were of observational, cross-sectional design. A total of nine themes (the need for information, the need to be heard, PD healthcare, emotional support, daily living, financial support, skills, care partner physical well-being, and respite care) were identified from qualitative data and all quantitative data could fit this framework. Quantitative data on the frequency of needs and when they arise over the course of PD were scarce. Only one quantitative study made use of a validated measurement instrument to measure care partner needs, the Family Needs Questionnaire.ConclusionsCare partner needs in PD are wide-ranging. A significant gap identified is the absence of quantitative data to determine the prevalence, timing, and factor contributing to the needs revealed by the qualitative research.

Parkinson's disease (PD) is a heterogeneous condition that presents variable clinical, neuropathological, and biomarker features. Disease progression can also vary significantly. It is essential to consider this heterogeneity when considering the medicines that people with Parkinson's (PwP) want. Potential PD medicines may be classed as disease modifying (DMT) or symptomatic (ST). The ultimate hope of PwP is that, sooner rather than later, the core of the PD pharmacopeia will provide personalised cocktails of drugs that not only deliver motor and non-motor symptom relief, but also slow, stop and then reverse disease progression. Generally, PwP are less interested in the scientific details, they are more focused on maintaining or improving quality of life. For those people at risk of PD, diagnosis in the pre-motor stage may herald the introduction of new medicines that arrest the progress of the disease before symptoms are manifest. One way to understand the medicines that PwP want is to ask which symptoms are the most bothersome, and target them accordingly. In practice, medicines that present optimal efficacy and convenience, at an affordable price, will be more likely to be accepted. Interactions between researchers and PwP should be encouraged in order to deepen the understanding of each other's needs and motivations. Finally, it is important to remember that PwP are individuals with emotions and concerns. As such, moderation in the communication of prognosis and of the potential of new medicines is essential, so that PwP can maintain hope rather than being misled by hype.

Although the need for better medications for the treatment of psychiatric symptoms in people with Parkinson's disease (PWP) is not disputed, the approach and targets for these medications needs further attention. Psychiatric symptoms occur at higher prevalence in PWP-many start in the prodromal phase of the disease-and have complex associations and interactions with the motor symptoms and their treatments, begging the question of whether they may be mechanistically connected. In this manuscript, we review the current evidence for pharmacologic treatments of psychiatric symptoms in PWP and explore the potential next steps needed to develop new medications for psychiatric symptoms in PD.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, and its prevalence has doubled in the past 25 years. New formulations of levodopa have recently been marketed that improved the ability to treat PD, but in the European Union, no new active substance for PD has been marketed since 2015, whilst two new agents have been marketed elsewhere. In spite of being the most treatable neurodegenerative disorder, several unmet medical needs still exists in PD, and efforts both from researchers, drug developers and regulators are needed to facilitate further developments in the field. There are several reasons that may account for the lack of new treatments for PD. Regulatory agencies provide scientific advice and have developed several programs to foster drug development. This manuscript discusses the main obstacles identified in the development process, the present status of approvals in European Union and the United States, and the presently available mechanisms to optimize drug development and marketing.

While significant progress has been made in treating Parkinson's disease (PD) symptoms, disease-modifying therapies (DMTs) have consistently failed. To address the underlying molecular mechanisms of PD, two biology-based criteria have been proposed: the "Synucleinopathy-Neurodegeneration-Genetics" (SynNeurGe) and "neuronal α-synuclein disease" (NSD) frameworks. Both frameworks emphasize the importance of biological markers over clinical symptoms. They recognize α-synuclein aggregation and genetic mutations (such as SNCA) as key diagnostic elements, with α-synuclein seed amplification assays (SAA) in cerebrospinal fluid (CSF) used to detect early disease stages. Dopaminergic neurodegeneration, measured by DAT imaging, is also central to both frameworks. These shared features aim to improve early diagnosis and precision medicine for PD. However, SynNeurGe provides a broader, more flexible framework that integrates α-synuclein pathology (S), neurodegeneration (N), and genetics (G), linked to clinical features (C). It aims to accommodate the complexity of PD and related Lewy body diseases, facilitating research on targeted DMTs. In contrast, NSD focuses specifically on PD and Lewy body dementia, introducing a staging system (NSD-ISS) based on biological markers and clinical impairment, helping track disease progression from preclinical to symptomatic stages. Despite their differences, both approaches highlight the need for more specific biomarkers and prospective studies to improve early intervention and personalized treatment. Harmonizing SynNeurGe and NSD concepts will be key in creating a universally accepted framework for precise PD diagnosis and therapy development.

This article reflects on two proposals to classify and stage Parkinson's disease (PD) and related conditions based on the presence of aggregated alpha-synuclein (ASN) detected by alpha-synuclein aggregation assay (SAA). The authors highlight the significant shortcomings of the proposals: detection of ASN by SAA is not specific of PD or other well-established clinical conditions; they do not allow prediction of clinical course and prognosis; and they are not suitable as an endpoint for clinical trials. To move forward with proposals reflecting so many uncertainties and unknowns will just sow confusion and misunderstanding within the PD community.

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.