Parkinson's Disease最新文献

Parkinson's disease is the second most common neurodegenerative disorder worldwide, as well as being the fastest-growing neurological disorder. Furthermore, PD corresponds to a significant burden on those diagnosed, their caregivers and healthcare systems, highlighting the critical need for early and accurate diagnosis. Effective diagnosis is essential not only for timely intervention but also for the development of disease-modifying treatments, which are currently unavailable for PD management. Historically, PD diagnosis and characterisation was heavily reliant on clinical presentation, which are only present after significant neurodegeneration has already occurred. Because of this, there is a consensus amongst the scientific community to transition away from clinical features and instead redefine PD diagnosis and staging based on biological presentation. This review discusses historical developments in clinical diagnostic criteria for PD as well as the role the recently developed frameworks such as SynNeurGe and the Neuronal alpha-Synuclein Disease-Integrated Staging System (NSD-ISS) will play in the further advancements of diagnostic practices. Furthermore, substantial research efforts into the pathobiology of PD have led to the development of novel in vivo assessments capable of detecting critical biomarkers of PD. Specialised imaging modalities, particularly nuclear imaging and magnetic resonance imaging, and biomarkers of α-synuclein pathology demonstrate high sensitivity and specificity for not only early diagnosis but also differential diagnosis between other parkinsonisms. Beyond diagnostic reforms, it is also important to identify markers that could serve as indicators of clinical course to aid in tailoring personalised treatment strategies. Therefore, this review also summarises key pathobiological hallmarks of PD beyond α-synuclein pathology, namely, dopaminergic denervation, copathologies and underlying indicators of neurodegeneration, such as iron deposition and neuroinflammation. Furthermore, strategies to assess such pathologies and their potential utility in the current paradigm shift towards biological characterisation are discussed.

Objectives: The Constipation Scoring System (CSS) is a validated tool for assessing constipation severity and has been previously applied in Parkinson's disease (PD) populations. However, comparative data on post-treatment CSS outcomes between individuals with and without PD remain lacking. This study aimed to compare post-treatment constipation severity between PD and non-PD patients in real-world clinical settings, with particular focus on neurology and gastroenterology outpatient clinics.

Methods: This retrospective chart review included 67 patients with PD from a neurology clinic and 50 non-PD patients with constipation from a gastroenterology clinic. Baseline characteristics were retrieved from electronic medical records. Follow-up assessments were conducted through direct or telephone interviews to evaluate constipation severity using the CSS. Additional data were collected on patients' self-reported intake of water, coffee, carbohydrates, and fiber, as well as exercise habits.

Results: Post-treatment CSS scores did not differ significantly between groups (PD: 6.07 ± 3.57 vs. non-PD: 5.24 ± 2.84; p = 0.172), with most participants classified as having mild constipation. No significant differences were observed in daily water, coffee, or fiber intake, or in exercise habits. However, non-PD patients reported significantly higher carbohydrate intake compared to PD patients (p = 0.003). PD patients more frequently reported long-standing constipation symptoms (≥ 6 years) than non-PD patients (p < 0.001). Patterns of laxative use also differed: while sennosides were most commonly used in both groups, non-PD patients more frequently used lactulose and mucilin, whereas PD patients more commonly used Unison enemas (p = 0.020) and milk of magnesia (p = 0.070).

Conclusion: Although constipation severity and treatment outcomes were comparable between PD and non-PD patients, PD patients more often experienced long-standing symptoms and demonstrated distinct patterns of laxative use. Prospective studies are warranted to evaluate standardized treatment protocols to better clarify treatment outcomes and inform clinical practice.

Background: Reduced social engagement is associated with increased risk of incident Parkinson's disease (PD). Online peer support provides opportunities to develop new social connections. A digital social forum was recently embedded within PREDICT-PD, an online UK cohort study that stratifies participants for risk of future PD, to explore the feasibility of digital social engagement as an intervention to modify PD risk.

Objective: This study reports on the content of messages exchanged on the forum to better understand how this was used and experienced.

Methods: 364 public posts from 218 distinct users were analysed using thematic analysis.

Results: Members created a sense of community through disclosing personal information and reaching out to others. Experiences were shared in relation to symptom appraisal, emotional impacts and routes to diagnosis. Practical advice, resources and information were exchanged to aid symptom management and proactive lifestyle changes. Users discussed their aspirations for timely diagnosis and treatment within healthcare, further research funding to aid prevention and treatment, and greater awareness of PD within society. Technical issues with the forum were reported, and accessibility was viewed as a potential barrier.

Conclusions: The online forum provided a peer support environment for people with similar health experiences to connect, exchange information and emotional support, and engage in discussions around political and social issues unique to PD. This highlights the potential of leveraging online peer support to promote social engagement in prodromal PD. Further research is needed to examine the effect on PD risk and develop accessible technologies.

This study explores the healthcare experiences of Australians with Parkinson's disease, focusing on healthcare access, symptom management and support networks. Despite the body of research on the experiences of PwPD, there is limited understanding of the specific challenges faced by Australians in accessing and navigating healthcare services. A national survey was conducted, and free-text responses to an optional open-ended question were analysed using thematic analysis to identify key themes in healthcare experiences and barriers. Seven themes were identified: Navigating Healthcare, Diagnostic Experiences, Symptom Experience and Management, Optimism and Resilience, Knowledge and Understanding of Parkinson's Disease, Necessitated Self-Advocacy, and Community-Driven Support. Participants reported difficulties in obtaining timely diagnoses, navigating healthcare services and accessing specialised care. Information gaps and inadequate patient-provider communication were also noted. Peer support networks were highlighted as crucial for coping and resilience, with a notable shift away from traditional familial support structures. Findings underscore systemic challenges in healthcare access and communication for Australian PwPD and suggest that enhancing peer support networks and improving care pathways could strengthen disease management and support.

Background: Parkinson's disease (PD) is characterized by motor symptoms but also includes nonmotor impairments such as sensory disturbances. Temporal discrimination (TD) deficits have been repeatedly demonstrated, while proprioceptive dysfunction is also common in PD. The exact significance of these alterations, and whether they represent related aspects of a common pathophysiological process, remains elusive.

Methods: We investigated somatosensory and kinesthetic TD as well as proprioceptive accuracy in 20 PD patients and compared 20 age- and sex-matched healthy controls (HCs). Somatosensory TD threshold (STDT) was assessed using paired cutaneous electrical stimuli and TD motor thresholds (TDMTs) by electrically induced wrist flexions. Proprioception was measured with two tasks requiring wrist flexion to predefined angles (LED task) or to reproduce angular ranges (ARROW task), without visual feedback. Clinical assessment comprised MDS-UPDRS III, Hoehn and Yahr stage, levodopa dosage, and disease duration.

Results: PD patients exhibited significantly elevated thresholds compared to HC for both STDT (120.3 ± 42.3 ms vs. 80.8 ± 17.1 ms, p = 0.001) and TDMT (107.1 ± 43.7 ms vs. 77.0 ± 16.3 ms, p = 0.011). Proprioceptive errors were also higher in PD for the LED (6.7° ± 2.2° vs. 3.2° ± 1.9°, p < 0.001) and ARROW tasks (14.2° ± 3.4° vs. 2.1° ± 0.8°,p < 0.001). No significant correlations were observed between TD, proprioceptive measures, or clinical severity indices.

Conclusions: PD patients show pronounced impairments in both TD and proprioceptive accuracy, confirming sensory processing deficits beyond motor dysfunction. The absence of correlations suggests distinct mechanisms, highlighting the need for further neurophysiological research.

Background: Online exercise groups for people with Parkinson's disease (PwP) are increasing in popularity, but little is known about PwP's experiences with them.

Objective: To explore the views and experiences of PwP who have utilised Parkinson's disease-specific online exercise groups.

Methods: A qualitative study utilising semistructured interviews and thematic analysis in a purposive sample of PwP who had participated in an online exercise group.

Results: Nine participants (5 females) with a mean age of 69.5 (63-78) years and a mean disease duration of 9.1 (3-20) years participated. Analysis revealed three overarching themes: 'Considerations of online exercise groups for PwP', which highlighted the pros and cons of attending online exercise classes; 'Online exercise class qualities', including the importance of a tailored approach, clearly communicated aims and the importance of a well-informed instructor; and 'Accessibility', which included considerations of convenience of access, costs and technological access.

Conclusion: Online exercise groups may play an important role in future Parkinson's disease management by offering greater access to exercise. They may also perpetuate inequalities for PwP and lack the social engagement many PwP seek. Hybrid group exercise, a combination of online and face-to-face classes, could provide this. Providers must develop classes that are tailored to PwP and delivered by well-informed instructors.

Background: Fatigue is a common and disabling nonmotor symptom of Parkinson's disease (PD), which significantly impacts gait and overall mobility. In spite of its clinical significance, the biomechanical consequences of different fatigue induction protocols on gait performance in PD are not yet well understood.

Objective: To systematically review fatigue induction protocols in gait studies of individuals with PD and to examine how different types of fatigue (local, general, and cognitive) and assessment methods influence gait outcomes.

Methods: In accordance with PRISMA guidelines registered under PROSPERO (CRD420251038246), five databases were systematically searched from January 2004 to March 2025. Seven studies met the inclusion criteria and were reviewed and analyzed through descriptive synthesis.

Results: Repeated sit-to-stand tasks were the most effective in inducing lower-limb fatigue and produced consistent changes in gait, including reduced stride length, slower speed, and impaired turning. General aerobic or functional tasks had inconsistent effects, and no study directly tested cognitive fatigue on gait. Fatigue assessment methods varied widely, including force decline, perceived exertion, and fatigue scales. Gait outcome measures were also heterogeneous, limiting comparability.

Conclusion: Targeted lower-limb fatigue protocols are effective in revealing gait impairments in PD. There is a clear need for standardized fatigue induction procedures and gait evaluation methods to improve consistency and comparability across research. Clinically, assessing gait under fatigue conditions may uncover subtle mobility impairments and inform more personalized rehabilitation strategies.

Background: There is a notable gap in racial and ethnic representation in Parkinson's disease (PD) research, particularly among American Indian and Alaska Native (AIAN) populations, despite a higher prevalence of PD in these groups. This study investigated research participation among AIAN individuals in terms of perceived access to research opportunities, willingness to participate, and potential concerns about participation.

Methods: Data were obtained from the online Fox Insight (FI) study. A total sample of 4412 individuals who self-reported their race as White (n = 4363) or AIAN (n = 49) were selected. The Attitudes and Beliefs Regarding Research and Genetic Testing for PD survey was administered to assess participants' attitudes and knowledge about the research process, opportunities, and preferences.

Results: A significantly smaller proportion of AIAN individuals (34.7%) reported concurrent or past participation in PD research compared with White non-AIAN participants (52.9%). Despite this lower participation rate and limited knowledge of research opportunities, a large majority of AIAN individuals (89.8%) expressed a willingness to participate in research. Additionally, both AIAN and White non-AIAN participants reported similar rates of concerns about research participation. Among AIAN individuals, the most common barriers were distance from research site, transportation, and time commitments.

Conclusion: These findings highlight that low research participation among AIAN individuals may be more associated with low engagement from the research community rather than unwillingness or relatively greater research concerns. Building stronger partnerships with tribal communities and involving community leaders to build trust may improve research representation among AIAN populations.

Objective: The main goal of this study is to explore the link between herpes simplex virus 1 (HSV-1) infection and Parkinson's disease (PD) from the genome-wide association studies (GWAS) data and find the shared molecular signature for mechanism understanding and drug repurposing from the transcriptomics data.

Methods: We used summary-level GWAS data for causal inference, exploring the association between herpes keratitis (mainly caused by HSV-1) and PD, and used transcriptomics data to study the shared molecular signature for mechanism understanding and drug repurposing.

Results: The causal inference analysis implied that HSV-1 infection is related to PD. The upregulated shared gene set between HSV-1 infection and PD is mainly enriched in neuroinflammation, while the downregulated shared gene set is mainly enriched in stem cell and cellular metabolism, and the drug repurposing targeted the shared molecular signature nalfurafine.

Conclusion: HSV-1 infection is related to PD, and these two diseases had shared molecular signature such as neuroinflammation and stem cell, which could be targeted for drug repurposing.

Oxidative stress is a major contributor to the pathogenesis of Parkinson's disease, promoting neuronal degeneration through the production of excessive reactive oxygen species. In this context, natural products such as essential oils are attracting increasing attention for their potential to protect neurons. Clove essential oil (CEO), which is extracted from the flower buds of the plant Syzygium aromaticum, is renowned for its antioxidant activity. This study aimed to investigate the chemical composition, antioxidant properties, and protective effects of CEO on SH-SY5Y cells, which are used as a cellular model of Parkinson's disease. The CEO was obtained by hydrodistillation (yield: 15%) and is primarily composed of eugenol (84.49%) and acetyl-eugenol (10.05%). Its antioxidant activity was confirmed via DPPH radical scavenging (IC₅₀ = 0.081 ± 0.001 mg/mL) and iron chelation (110.32 ± 0.67 mg EDTA equivalent/g essential oil (EO)). qRT-PCR, Western blot, and slot blot techniques demonstrated that CEO pretreatment at concentrations of 2.5, 5, and 10 μg/mL significantly reduced 6-OHDA-induced oxidative DNA damage and restored the gene and protein expression of key antioxidant enzymes (GPx1, GPx4, SOD1, and CAT). These results highlight the powerful antioxidant and neuroprotective properties of CEO, supporting its potential as a therapeutic agent for neurodegenerative disorders related to oxidative stress, such as Parkinson's disease.