Journal of Parkinson's disease最新文献

BackgroundParkinson's disease (PD) is the second most prevalent neurodegenerative disorder with broad manifestations of motor and non-motor symptoms. While significant progress has been made in assessing motor dysfunction through wearable sensors, less attention has been directed towards bulbar issues like swallowing difficulties.ObjectiveWe introduce a digital health solution leveraging advanced acousto-mechanic (ADAM) sensors capable of comprehensively evaluating motor and bulbar dysfunction in PD that additionally offers artificial intelligence-driven haptic biofeedback to enhance swallowing frequency.MethodsThe swallow detection algorithm developed with data from n = 58 healthy subjects yielded an F1 score of 0.89 for swallow event detection.ResultsIn a pilot study with PD patients (n = 20) experiencing mild (60%) or moderate (40%) dysphagia, the use of ADAM sensors with biofeedback significantly increased swallow frequency by 45%, from 0.77 to 1.10 swallows per minute (p < 0.0001). The sensors demonstrated high sensitivity (89%) and a strong correlation with visual observations by speech language pathologists (r = 0.92, p < 0.05), with 100% agreement on respiratory-swallow phase patterning. Feedback from patients and caregivers underscored the utility and comfort of the technology.ConclusionsThis tailored digital health solution not only monitors PD symptoms but also holds potential as an assistive device, marking a significant step in improving the quality of life for PD patients.

BackgroundCircular RNAs (circRNAs) constitute a distinctive subclass of RNAs that are known for their regulatory roles in fundamental cellular processes. Due to their increased stability and ubiquitous expression, circular RNAs have been widely studied as potential molecular targets in various diseases, including neurodegenerative diseases. While several studies have found differentially expressed circRNAs associated with Parkinson's disease (PD), none has looked specifically into PD progression.ObjectiveTo elucidate the role of circRNAs in the progression of PD by identifying dysregulated circRNAs associated with PD progression and to pinpoint potential downstream miRNAs and associated differentially expressed gene targets.MethodsIn this study, we have utilized large-scale, longitudinal, and deep RNA-seq data from two independent cohorts, namely the Parkinson's Progression Marker Initiative (PPMI) and the Parkinson's Disease Biomarker Program (PDBP), to characterize circRNA expression in patients of early PD stage.ResultsWe identified six circRNAs significantly differentially expressed in whole blood samples obtained from PD patients over time. Additionally, we were able to map a competing endogenous RNA (ceRNA) network with potential downstream miRNA-mRNA targets and, with the help of co-expression analysis, to identify genes associated with PD progression. Our findings provide compelling evidence for a dysregulated circRNA interactome as an indicator of PD progression, with changes in the expression of these circRNAs and downstream gene targets being significantly associated with changes in UPDRS III scores in PD patients.ConclusionsOur results strongly indicate the association of circular RNAs with PD progression and emphasize its significance as a critical molecular marker.

BackgroundThe patient experience of Parkinson's disease (PD) is heterogeneous, with limited prognostic tools to predict individual outcomes, leading to significant uncertainty for people with PD. Under-recognition of both psychosocial and biological drivers of fear and uncertainty in Parkinson's disease (PD) by clinicians may further contribute to patient distress.ObjectiveThe objective of the present study is to investigate fear and uncertainty in people with PD.MethodsIn-depth interviews were conducted with twenty people with PD (11 semi-structured, 9 guided/prompted). Thematic analysis organized the fears/uncertainties by topic as well as by contextual factors such as the timing of the fear (e.g., active or anticipatory; at the time of diagnosis or developed subsequent to diagnosis) and the lexicon used to describe it.ResultsParticipants expressed a wide range of fears and uncertainties about their future and quality of life with PD, which shifted with disease progression. Most fears were anticipatory rather than in response to current concerns. Participants reported substantial psychosocial influence from media personalities or family/friends with PD. Most participants reported that they had not disclosed their fears to their healthcare providers.ConclusionsClinicians caring for people with PD should be aware of a range of often-unspoken fears and uncertainties, which may carry a substantial psychosocial burden. Open acknowledgement and normalization by clinicians may help patients feel less isolated in their disease.

BackgroundPhysical activity (PA) is beneficial for people with Parkinson's (PwP); however, many are classed as sedentary. PDConnect is an online multicomponent intervention combining 1:1 physiotherapy and group-based PA combined with education, behavior change and self-management strategies, promoting PA and self-management among PwP.ObjectiveTo assess feasibility and acceptability of PDConnect.MethodsMixed methods study involving 31 PwP randomly allocated to: (i) usual care: physiotherapy once a week for six weeks, and (ii) PDConnect: physiotherapy once a week for six weeks, followed by 12 weekly sessions of group-based PA, followed by three monthly Teams calls to support engagement. Outcomes included intervention feasibility and acceptability (primary) assessed via survey and interviews; PA, motor, non-motor symptoms, and health and well-being (secondary) assessed at baseline, and at six, 18, and 30 weeks. Fidelity was accessed by post hoc video analysis.ResultsOnline delivery of PDConnect was feasible and safe. Participant retention was 74%. Response rate of self-reported measures was 97%. 95% of participants returned completed activity diaries. Attendance was high, with all participants recommending PDConnect. PDConnect participants reported improved flexibility, muscle strength, and endurance as well as increased PA confidence, PA levels and knowledge of Parkinson's disease. Half of PDConnect participants reported that they were much improved compared to 10% of usual care participants. Small to large effect sizes in PA (d = 0.03) and UPDRS (d = 0.96) ES) were reported, which warrant further exploration in an appropriately powered study.ConclusionsPDConnect is feasible and acceptable among PwP. A future large-scale trial is required to determine the effectiveness of PDConnect.

BackgroundThe motor reserve estimates (MRes) derived from a residual approach correlate with motor severity in Parkinson's disease (PD), leaving the independent effect of motor reserve on clinical outcomes unclear.ObjectiveInvestigate the independent influence of motor reserve on the long-term outcome.MethodsUsing the Parkinson's Progression Markers Initiative (PPMI) and Pusan National University Hospital (PNUH) datasets, we investigated the association of MRes with progression of motor severity as well as risk of phenoconversion to Hoehn & Yahr (H&Y) stage 3. Two MRes types were calculated: (1) original MRes, negative conversion of standardized residuals from a generalized linear model (GLM) between putaminal dopamine transporter (DAT) levels and motor severity, and (2) modified MRes, standardized residuals from the GLM between original MRes and motor scores.ResultsOriginal MRes correlated with baseline motor scores, while modified MRes did not. Modified MRes in both cohorts were associated with a rapid increase in motor severity (linear mixed effect model, interaction between MRes and disease duration; PPMI, Movement Disorder Society sponsored Unified Parkinson Disease Rating Scale part III [MDS-UPDRS III], estimate 2.248 × 10^-3, p < 0.001; PNUH, UPDRS III, estimate 0.027, p = 0.014) In both cohorts, Kaplan-Meier plots showed high modified MRes indicated higher risk of progression to H&Y stage 3. Mediation models using original MRes agreed that high MRes were associated with an accelerated increase in motor scores.ConclusionsIndependent of baseline motor severity, MRes were associated with rapid motor deterioration and high risk of progression to H&Y stage 3.

BackgroundTremor is prevalent among older adults and is suggested to be associated with the subsequent development of Parkinson's disease (PD). However, prospective evidence for the association is scarce.ObjectiveThis population-based prospective study aimed to estimate PD risk and to explore predictive factors for PD conversion in community-dwelling older people with tremor.MethodsThe study was based on the Beijing Longitudinal Study on Aging (BLSA) II. Tremor was assessed using a validated self-administered method. Participants without parkinsonism and with any tremor were followed for an average of 7.7 years. The standardized incidence ratio (SIR) was used to estimate the risk of developing PD in older people with tremor, with age- and sex-specific incidence rates of PD in the general Chinese population as a reference. Risk factors, prodromal symptoms, and tremor features were assessed to identify predictors for incident PD.ResultsSeventeen (8.4%) of 202 participants with tremor developed parkinsonism, including 9 (4.4%) diagnosed with PD. The presence of any tremor was associated with an increased risk of developing PD (SIR: 3.12, 95% confidence interval [CI]: 1.52-5.73). Sensitivity analyses yielded similar results. Probable REM sleep behavior disorder (RBD), identified using the RBD Questionnaire-Hong Kong, and self-report of new-onset rest tremor predicted PD conversion.ConclusionsTremor is associated with an elevated risk of PD in the general older population. Screening for RBD and monitoring the evolution of tremor characteristics using simple questionnaires may help identify individuals at high risk for PD among community-dwelling older adults with tremor.

BackgroundRemote monitoring solutions (RMS) have the potential to improve Parkinson's disease (PD) management by enabling continuous symptom tracking and personalized care. Understanding patient preferences for RMS features is essential for successful implementation.ObjectiveThis study aimed to investigate the preferences of people with Parkinson's disease (PwP) for RMS features and identify preference heterogeneity across distinct patient subgroups.MethodsFrom November 2023 to February 2024, a discrete choice experiment (DCE) was conducted among PwP in Finland and Italy to elicit preferences for RMS attributes, including monitoring frequency, time spent filling questionnaires, home video recordings, and clinical benefits (delay in advanced symptom onset). Latent class analysis (LCA) was used to identify subgroups with distinct preference patterns, and adoption probabilities under varying RMS scenarios were estimated.ResultsA total of 411 PwP participated, revealing significant heterogeneity in RMS preferences. While clinical benefits, particularly delaying advanced symptom onset, were the most valued attribute overall, preferences diverged across subgroups. Some participants strongly preferred home video recordings, whereas others expressed aversion to this feature. A smaller subgroup exhibited reluctance toward RMS adoption, regardless of its benefits.ConclusionsPwP generally view RMS favorably, but preferences for specific features vary substantially across subgroups. Clinical benefits are a key driver of adoption, while home video recordings elicit both strong preference and aversion, highlighting the impracticality of a one-size-fits-all approach. Tailoring RMS to diverse patient needs, addressing concerns, and enhancing usability through customization are essential for successful implementation and widespread acceptance in PD management.

BackgroundTremor is reported by people with Parkinson's disease (PwP) as being one of the most troublesome symptoms.ObjectiveTo characterize the PwP experience of tremor.MethodsAn internet-based survey of PwP living with tremor was conducted in the US, from September 2023 to March 2024.ResultsSurvey responses from 634 respondents (PwP = 599; care partner = 35) were analyzed. Most (93%) PwP had tremor in their upper extremities and of these, 59% reported ≥2 tremor subtypes (rest/postural/kinetic). Overall, 24% reported little or no effect of medication and a further 25% reported that medication only somewhat improved their tremor. At least mild functional impairment due to tremor was reported by 65% of PwP and most indicated that ≥1 daily activity (83%), sensory experience (77%), or psychosocial function (92%) was impacted. Multinomial logistic regression analyses revealed that the odds [95%CI] of reporting severe functional impairment due to tremor (vs. slight) were increased by worse tremor in the dominant hand (4.9 [1.36, 17.72]); presence of OFF-time (4.7 [1.22, 18.30]), number of body parts affected (2.0 [1.45, 2.88]) and lack of medication effect (1.6 [0.30, 8.22]). The presence of all three tremor subtypes was associated with increased odds of being "very dissatisfied" with quality of life (21.5 [2.51, 183.44]).ConclusionsResults from this survey demonstrate that tremor in PD is often more than a rest tremor and frequently impacts function and activities of daily living. Medication response is inadequate in about half of cases, highlighting that effective treatment of tremor is an important unmet need.