Journal of Parkinson's disease最新文献

The traditional approach of using double-blind, placebo controlled, parallel group trial designs has confirmed the efficacy of a large number of agents in relieving the symptoms of Parkinson's disease (PD) but has not, to date, led to the discovery of any disease-modifying treatments for PD. There are multiple potential reasons underlying the failure to find disease modifying approaches, which may in part relate to; inadequate understanding of PD pathophysiology and therefore inappropriate target selection; the possibility that even good candidate drugs may simply fail to reach and to ultimately engage with their putative targets at the required dose; and the significant heterogeneity of the disease both in terms of its pathophysiology and its motor and non-motor symptoms. PD also has some additional challenges that may be addressed by careful consideration of trial design. This includes; its generally slow rate of disease progression necessitating long follow-up times to identify evidence of disease slowing; lack of understanding regarding the optimal stage of disease that might be most amenable to intervention; as well as lack of consensus regarding which outcome measures best capture patient relevant disease progression, and which biomarkers might consistently and objectively provide the earliest indication of disease progression. In this review we will discuss these issues and potential approaches that may help in the evolution of clinical trial design and thus ultimately provide a pathway to increase the likelihood of successful identification of disease-modifying treatments for Parkinson's disease.

BackgroundExergaming has shown benefits in Parkinson's disease (PD) rehabilitation; however, its feasibility and potential effectiveness for people with moderate to advanced PD remain unclear.ObjectiveTo assess the feasibility and potential effectiveness of a universally designed exergame program in people with moderate to advanced PD.MethodsThis evaluator-blind, parallel randomized controlled trial was conducted at four specialized PD care facilities in Japan. Fifty-six participants (Hoehn & Yahr stages III-V) were randomly assigned (1:1) to the intervention or control group. The intervention group participated in an 8-week, universally designed exergame program alongside a standardized rehabilitation program. Sessions were conducted in supervised groups and lasted 15 min, thrice a week. Acceptability was assessed with a questionnaire. Adherence was based on attendance. Safety was monitored, and session-level experience (fatigue, effort, perceived progress, enjoyment) was assessed. Predefined criteria were applied for acceptability, attendance adherence, and session-level experience. The potential effectiveness was assessed by changes in health-related quality of life (HR-QoL), motor function, cognitive function, social engagement, and loneliness.ResultsThe final analysis included 37 participants. The program was judged acceptable by 84% participants, and the attendance adherence was 99.7%. No intervention-related adverse events occurred. Acceptability, attendance adherence, and session-level experience met the prespecified criteria. Exploratory findings suggested potential effectiveness for HR-QoL and loneliness, whereas no significant changes were observed in motor or cognitive function scores.ConclusionThis pilot study supports the feasibility of our exergame program for people with moderate to advanced PD and shows its potential effectiveness for HR-QoL/loneliness.Trial RegistrationUMIN Clinical Trials Registry (UMIN-CTR), https://www.umin.ac.jp/ctr/, UMIN000054292 (registered on May 1, 2024).

BackgroundFreezing of gait (FOG) in Parkinson's disease (PD) is a major cause of disability and falls and often responds incompletely to conventional therapy. Rehabilitative interventions including cognitive strategies and sensory cueing are efficacious, but difficulties in learning impair executing these strategies. Transcranial direct current stimulation (tDCS) enhances motor task learning and might enhance the efficacy of rehabilitative interventions.ObjectiveWe assessed whether tDCS can enhance the efficacy of physiotherapy for FOG in PD.MethodsIn a randomized, double-blind, controlled study, anodal tDCS (pre-/motor cortex) or sham-tDCS were delivered combined with a standardized rehabilitative intervention in 24 PD patients with FOG for eight sessions within four weeks. Clinical assessment included walking a Parcourse, timed gait tests, FOG questionary, and clinical scales at baseline, across the interventions with a follow-up 3-months after the last intervention.ResultsNineteen PD patients with FOG completed the study. TDCS combined with physiotherapy reduced FOG, but not more than physiotherapy aloneConclusionCombining tDCS with physiotherapy did not enhance its efficacy in reducing FOG.

BackgroundBoth Mediterranean and ketogenic diets have been proposed as nutritional interventions in Parkinson's disease (PD). Combined approaches may offer maximal benefits.ObjectiveAssess the feasibility, safety and exploratory efficacy of two ketogenic interventions, using a Mediterranean diet base, in individuals with PD (PwP).MethodsIn this Phase II, random-order crossover study, PwP followed two 8-week dietary interventions, separated by an 8-week washout: 1) a high-fat, low-carbohydrate Mediterranean diet (MeDi-KD) and 2) a standard Mediterranean diet supplemented with medium chain triglycerides (MeDi-MCT).ResultsOf 52 participants randomized, 48 started the trial. Forty-one (79%) participants completed at least one, whereas only 33 (63%) completed both intervention phases. There were no intervention-related serious adverse events, nor any significant changes in plasma lipid profiles. Seventy-three percent and 92% of participants reported deviating from the MeDi-KD and MeDi-MCT no more than a few times per month, respectively. Moderate Mediterranean Diet Adherence Screener scores of 6.7 (SD: 1.6) and 7.2 (SD: 2.3) were achieved during the MeDi-KD and MeDi-MCT, respectively, out of a maximum of 14. Fifty percent of participants were in nutritional ketosis ([beta-hydroxybutyrate] ([BHB]) > 0.5 mM) at follow-up for the MeDi-KD, as compared with only 1 (3%) participant following the MeDi-MCT. MDS-UPDRS Part II and IV scores decreased by a mean of -1.4 (SD: 4.2; p = 0.039) and -1.0 (SD: 3.0; p = 0.044) points, respectively, following the MeDi-MCT.ConclusionsWhile both Mediterranean-ketogenic interventions appear safe in the short-term in PwP, their feasibility is called into question by a high study dropout rate (37%) and modest adherence. Preliminary benefits observed in patient-reported motor experiences were paradoxically limited to the MCT-supplemented MeDi, in which ketosis was not reliably achieved. Together, our findings indicate the need to refine behavioral strategies to optimize dietary awareness and adherence in future trials.Trial RegistrationThe trial was registered on ClinicalTrials.gov: NCT05469997.

Parkinson's disease is the fastest growing neurodegenerative disorder worldwide, yet care delivery remains fragmented and inequitable. We propose a new construct called the Parkinson's Universe. It is a person-centered model that reimagines care as a coordinated universe. This commentary summarizes the model's elements including the patient as the sun or center of the universe, the caregiver as Mercury, the social support and multidisciplinary healthcare professionals as the other planets, mission control as care coordination, stigma as Pluto, barriers as asteroids, supportive technology as satellites, and support networks as stars. We discuss clinical and policy implications, emphasizing the urgent need to move beyond the fragmented gatekeeper system to one that is proactive, equitable, and holistic. As such, the Parkinson's Universe provides a blueprint for integrating innovation, advocacy, and multidisciplinary care. The model also has relevance across other complex chronic diseases.

Background: Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder, so it is likely that people with PD (PwPD) face increasing disability. PwPD thus experience various degrees of fear of progression (FoP), which can become dysfunctional. Objective: This study aims to examine the prevalence of and contributing factors to dysfunctional FoP in PwPD. Methods: The Fear of Progression Questionnaire-Short Form (FoP-Q-SF) was administered along with further questionnaires for non-motor symptoms; PD motor symptoms as reported by the Unified Parkinson's Disease Rating Scale Part III (UPDRS III) were obtained from patient charts. Results: 28% of the 105 PwPD (mean age 66 years, 56% Hoehn & Yahr stage I/II) were categorized as experiencing dysfunctional levels of FoP using the established cut-off score of ≥34. Our analyses revealed that the FoP-Q-SF underestimates the prevalence of dysfunctional FoP in older and non-working PwPD. Using a more appropriate cut-off, 33% of PwPD are classified as having dysfunctional levels of FoP. We found strong correlations of FoP with measures of anxiety, depression and quality of life. Disease duration was secondary to these factors. We found no associations between FoP and motor symptoms. Conclusions: Our findings confirm that dysfunctional FoP significantly impacts the psychological well-being of PwPD, affecting one in three PwPD and contributing to heightened anxiety, depression, and reduced quality of life. Future validation studies are needed to confirm the cut-off value proposed here and to enable a better integration of the concept of FoP into routine care for PwPD.

BackgroundA key challenge in trials targeting disease modification in Parkinson's disease (PD) is the lack of sensitive, precise, and patient-relevant outcome measures. Digital mobility outcomes (DMOs), captured using body-worn devices, offer a novel, objective means to assess real-world gait and mobility-domains often impaired early in PD. The Mobilise-D consortium was established to develop and validate DMOs in PD and other conditions.ObjectiveTo describe DMOs in a large, representative international cohort of individuals with PD and compare to controls and across disease stage; and to determine compliance and feasibility.MethodsAs part of the Mobilise-D Clinical Validation and Extension Studies, real-world mobility of individuals with PD (n = 601) and matched controls (n = 232) was assessed using a single wearable device for seven days. Data were processed to yield 24 technically validated DMOs, representing different domains of real-world walking and mobility performance.ResultsDMO data were available for 531 PD and 221 controls. Significant differences between the groups were observed in 20 of 24 DMOs. Compared to controls, PD participants exhibited shorter daily walking duration and lower step counts, walking at a higher cadence and in fewer walking bouts per day. Findings also varied by disease severity, with differences observed particularly between controls vs. mild (Hoehn and Yahr stage I-II) and mild vs. moderate (Hoehn and Yahr stage III) disease. Compliance rates were high.ConclusionsDistinct DMO patterns across PD severity and between PD and controls support their utility as sensitive, scalable outcome measures for future clinical trials and therapeutic development.

Parkinson's disease is a common neurodegenerative disorder, which is characterised by motor features, many of which relate to the loss of the dopaminergic nigrostriatal pathway. The use of grafted cells to replace the lost dopaminergic neurons as a therapy for Parkinson's has been explored since the 1980s, with mixed clinical outcomes. Much of the heterogeneity in outcomes has been related to the major problems with the cell source for these trials, being derived from human fetal brain tissue. It is, however, now possible to derive authentic midbrain dopamine cells from human pluripotent stem cells and several first-in-human clinical trials are now underway to explore this approach.

The present study aimed to provide an overview of the experiences of couples coping with Parkinson's disease (PD), along with a synthesis of the mechanisms involved in changes within the couple's relationship in the context of PD. These mechanisms were identified using a qualitative approach: dyadic Interpretative Phenomenological Analysis. Forty-five couples separated in three groups according to disease progression, participated. Interviews were conducted separately with each partner. After individual analysis, the salient individual and dyadic phenomena were identified at the group level. Three mechanisms emerged regardless of disease stage: having divergent views on PD, being united and cohesive, avoiding discussing the disease. Other mechanisms were more specific to some stages. Even with few consequences on independence, PD can significantly impact the couple's dynamics. In most cases, strategies for adjusting to PD and/or the changes it causes in the couple's relationship lead to tension and negative emotions. Better support for both partners is needed to promote better adjustment strategies from the early stage of PD.