Parkinsonism & Related Disorders

BackgroundThe availability of deep brain stimulation (DBS), a highly efficacious treatment for several movement disorders, remains low in developing countries, with scarce data available on utilization and outcomes. ObjectivesWe characterized the DBS cohort and outcomes at a Malaysian quaternary medical centre. MethodsA retrospective chart review was done on DBS-related surgery at the University of Malaya, including clinico-demographic, genetics, and outcomes data focusing on post-operative medication reduction and complications. Results149 Parkinsons disease (PD) patients underwent DBS targeting the subthalamic nucleus. Six had globus pallidus internus DBS (primarily for dystonia). Only 16.1% of cases were government-funded. Of the 133 PD patients operated in the past decade (2013-2022), 25 (18.8%) had disease duration <5 years. At 6-12 months post-DBS, median levodopa-equivalent daily dosage (LEDD) reduction was 440.5 [418.9] mg/day, corresponding to a reduction of [&ge;]50% and [&ge;]30% in 42.2% and 69.8% of patients, respectively. LEDD reductions were larger in the early-onset and short-duration subgroups. Three patients (1.9% of 155) had symptomatic intracranial hemorrhage, resulting in stroke in two. Pathogenic monogenic or GBA1 variants were detected in 12/61 (19.7%) of patients tested, mostly comprising the "severe" GBA1 variant p.L483P (14.8%). ConclusionThis is the largest report on DBS from Southeast Asia. The procedures were effective, and complication rates on par with international norms. Our study found a high frequency of GBA1-PD; and included a substantial number of patients with short-duration PD, who had good outcomes. It also highlights the inequity of access to device-aided therapy.

BackgroundLevodopa-induced dyskinesia (LID) is a common motor complication of levodopa therapy in patients with Parkinsons disease (PD). Doxycycline is a widely used and inexpensive tetracycline with anti-inflammatory properties. ObjectiveEvaluate the efficacy and safety of doxycycline in patients with PD and LID. MethodsThis was an open-label, single-center, phase 2 proof-of-concept study in patients with PD with mild functional impact of dyskinesia, which used levodopa three times daily, in a movement disorders clinic in Brazil. Participants were treated with doxycycline 200 mg/day for 12 weeks, with evaluations in baseline, week 4, and week 12 of treatment. The primary outcome measure was the change from baseline in the Unified Dyskinesia Rating Scale (UDysRS) total score at week 12, evaluated by two blinded raters. Key secondary outcomes measures were OFF time and ON time with troublesome dyskinesia in the PD home diary. ResultsEight patients with PD were treated and evaluated. Doxycycline 200 mg/day reduced the UDysRS total score in week 12, compared with baseline (Friedmans X2 = 9.6, p = 0.008). Further, doxycycline reduced the ON time with troublesome dyskinesia (Friedmans X2 = 10.8, p = 0.004) without worsening parkinsonism. There were no severe adverse events, and dyspepsia was the commonest event. ConclusionsDoxycycline was effective in reducing LID and safe after a 12-week treatment. Further well-designed placebo-controlled clinical trials with a longer duration and a larger number of participants are needed.

BackgroundParkinsons Disease (PD) patients with postural instability and gait disorder (PIGD) subtype are at increased risk for falls compared to the tremor-dominant subtype. We aimed to establish an easy clinical balance tool to rapidly and reliably identify PIGD patients, potentially important for directing healthcare resources or research phenotyping. Methods45 consecutive patients with PD completed clinical testing including Romberg, tandem stance, single leg stance, 360{degrees} turning and 10-meter walking. MDS-UPDRS part II and III, collected as part of regular follow-up, was used to classify disease subtype. Multinominal logistic regression models were fitted to find optimal subtype predictors and compared using receiver operating characteristic (ROC) curves. ResultsUnassisted tandem stand duration and time to turn 360{degrees} were significantly different between PIGD and tremor dominant subtypes. Both tandem standing and 360{degrees} turning showed very high predictive accuracy to predict PD subtype with an area under the ROC curve (AUC) of 86.6% and 88% respectively, which increased to 91.4% by combining both measures. Optimal cut-off values for identifying PD subtypes were tandem standing less than 20s and 360{degrees} turning longer than 6.5s. ConclusionTandem stand duration and 360{degrees} turning are easy to apply clinical tests that rapidly identify PD patients with PIGD subtype with high sensitivity and specificity. These findings may be useful in the clinic to identify PD patients current falls risk or screening for research studies. Plain Language SummaryBalance problems and falls are common in late-stage Parkinsons Disease, affecting nearly 70% of patients 10 years post-diagnosis. In contrast, Parkinsons patients who complain mainly of shaking (tremor) are less liable to fall. We set out to find an easy and reliable bedside test to distinguish patients at risk of falls with early Parkinsons. This is important so that resources can be targeted to patients in need of support such as physiotherapy and fall prevention. 45 patients with Parkinsons disease participated in this study and completed a battery of balance tests completed within the time of their regular follow-up appointment. We found that tandem standing duration - a test where patient stand still in the heel-to-toe position - and time taken to complete a full circle, were highly reliable in detecting patients with balance and gait problems. Specifically, patients with balance and gait problems were unable to tandem stand for more than 20 seconds and took more than 6.5 seconds to turn a full circle. Together, these two tests that take a minute to complete in the clinic, and may help improve the care for patients with Parkinsons as a quick screening tool to identify Parkinsons disease at risk of falls.

BackgroundFreezing of Gait (FOG) is a motor symptom frequently observed in advanced Parkinsons disease. However, due to its paroxysmal nature and diverse presentation, assessing FOG in a clinical setting can be challenging. Before FOG can be fully investigated, it is critical that a reliable experimental setting is established in which FOG can be evoked in a standardised manner, but the efficacy of various gait tasks and triggers for eliciting FOG remains unclear. ObjectivesThis study aimed to conduct a systematic review of the existing literature and evaluate the available evidence for the relationship between specific motor tasks, triggers, and FOG episodes in individuals with Parkinsons disease (PwPD). MethodsWe conducted a literature search on four online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) using the keywords "Parkinsons disease," "Freezing of Gait," and "triggers." A total of 128 articles met the inclusion criteria and were included in our analysis. ResultsThe review found that a wide range of gait tasks were employed in gait assessment studies on PD patients. However, three tasks (turning, dual tasking, and straight walking) were the most frequently used. Turning (28%) appears to be the most effective trigger for eliciting FOG in PwPD, followed by walking through a doorway (14%) and dual tasking (10%). ConclusionsThis review thereby supports the use of turning especially 360 degrees as a reliable trigger for FOG in PwPD. This could be beneficial to clinicians during clinical evaluations and researchers who wish to assess FOG in a laboratory environment.

BackgroundEffective, measurable, and non-invasive treatments for motor symptoms, gait and balance difficulties, and associated non-motor burden in Parkinsons disease (PD) remain limited. We aimed to assess the usability, safety/tolerability, and clinical efficacy of CUE1+, a wearable cueing and vibrotactile stimulation non-invasive device, in people with PD. MethodsThis 12-week, double-blind, randomised controlled trial was conducted at two UK sites in adults with idiopathic PD. Participants were randomly assigned (1:1) to receive either an active CUE1+ device or a sham device, worn on the sternum for 8 hours daily. Participants, investigators, and assessors were blinded to treatment allocation. The primary outcomes were usability and safety/tolerability of CUE1+. Secondary outcomes, including Movement Disorder Society-sponsored revision of the Unified PD Rating Scale (MDS-UPDRS) Part III, were assessed in the ON-medication state at baseline and week 13. FindingsFifty participants were randomised to sham stimulation (Group A; n=25) or active CUE1+ stimulation (Group B; n=25). Median age was 70.0 years (IQR 65.0-75.5) in Group A and 68.0 years (62.0-75.0) in Group B. Group A included 14 (56%) men; Group B, 13 (52%) men. Four participants (8.0%) discontinued: three (6.3%) from Group A, one (2.0%) from Group B. Compliance to allocated intervention was equally excellent in both groups. Mild, transient skin irritation occurred in two participants (4.2%). MDS-UPDRS Part III scores improved by -4.5 points (95%CI: -8.7, -0.4; p=0.043), in Group A and -15.6 points (95%CI: - 20.3, -10.9; p<0.0001) in Group B, with a between-group difference of 11.08 points (95%CI: 4.85-17.31; p=0.002). InterpretationCUE1+ is a safe and well-tolerated non-invasive device that improves motor and non-motor outcomes in PD. These findings suggest a potential therapeutic benefit and support further evaluation in large-scale RCTs and consideration for integration into health care pathways. FundingUKRI Knowledge Transfer Partnership, 2021-2022, round 4 and Charco Neurotech Ltd.

The number of people living with Parkinsons disease (PD) is expected to rise in the coming years. This study analyzed health care utilization patterns of Medicare beneficiaries with a PD diagnosis (ICD-10 code G20) who were enrolled in 2019. Utilization analysis included PD-related specialists and primary care physicians, therapy services, and mental health services. We found 685,116 (1.2%) Medicare beneficiaries had PD (56.3% male, 77.9% over age 70, 85.3% White, and 16.0% rural residents). Few Medicare beneficiaries with PD sought care from a movement disorder specialist (MDS) (9.1%); another 50.9% visited a general neurologist. Results reveal low utilization rates for therapy and even lower rates for mental health services. Overall healthcare utilization varied significantly by demographic group with women, people of color, and rural residents being less likely to access specialist care. Our findings emphasize the need for further research on population-specific barriers to accessing PD-related health care.

BackgroundIn addition to motor deficits, Parkinsons disease (PD) may cause perceptual impairments. The role of perceptual impairments in sensorimotor function is unclear, and has typically been studied in single-joint motions. Research Question: We hypothesized that perception of whole-body motion is impaired in PD and contributes to balance impairments. We tested 1) whether directional acuity to whole body perturbations during standing was worse in people with PD compared to neurotypical older adults (NOA), and 2) whether balance ability, as assessed by the MiniBESTest, was associated with poor directional acuity in either group. MethodsParticipants were exposed to pairs of support-surface translation perturbations in a two-alternative forced choice testing paradigm developed previously in a young healthy population. The first perturbation of each pair was directly backward and the second deviated to the left or right (1{degrees}-44{degrees}). Participants judged and reported whether the perturbations in each pair were in the "same" or "different" direction. This information was used to calculate directional acuity thresholds corresponding to "just-noticeable differences" in perturbation direction. Linear mixed models determined associations between directional thresholds and clinical variables including MDS UPDRS-III score, age, and MiniBESTest score. Results: 20 PD (64{+/-}7 y, 12 male, [&gt;=]12 hours since last intake of antiparkinsonian medications) and 12 NOA (64{+/-}8, 6 male) were assessed. Directional thresholds were higher (worse) among PD participants (17.6{+/-}5.9{degrees} vs. 12.8{+/-}3.3{degrees}, P<0.01). Linear mixed models further showed that higher thresholds were associated with MDS UPDRS-III score (P<0.01), and were associated with poorer balance ability among PD participants (P<0.01), but not among NOA participants (P=0.40). Significance: Perception of whole-body motion is impaired in PD and may contribute to impaired balance and falls.

Functionality is considered the third health indicator, complementing the traditional mortality and morbidity metrics. However, functionality is rarely assessed systematically in Parkinsons disease (PD) clinical practice and research, where symptom-based scales predominate. Identifying declines across various dimensions of functionality in PD is essential for patient education, disease management, and guiding new intervention strategies. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a comprehensive assessment tool developed by the World Health Organization (WHO) based on the International Classification of Functioning, Disability and Health (ICF) to standardize the measurement of functionality and disability impacts across diverse health conditions and cultural contexts. This study aimed to characterize functionality across PD severity stages using the WHODAS 2.0, independent of age, sex, socioeconomic status (SEC), and education. A total of 352 patients were divided into four clinically severity PD stage groups according to the Hoehn & Yahr (H&Y) scale. The age, sex, SEC and education levels were controlled to guarantee paired groups. All participants were evaluated remotely using the Telephone - Montreal Cognitive Assessment (T-MoCA), Beck Depression Inventory (BDI), Movement Disorder Society - Unified Parkinsons Disease Rating Scale, Part I (MDS-UPDRS I) and Part II (MDS-UPDRS II) and WHODAS 2.0. The most affected functionality dimensions were Mobility, Activities of Daily Life related to the Household, and Participation. The nonparametric Kruskal-Wallis test revealed a significant effect of the group for all functionality dimensions. Notably, Mobility, Activities of Daily Life related to the Household, and Self-Care showed a gradual decline starting from stage 1 of H&Y. In contrast, Cognition, Getting Along and Participation exhibited progressive impairment only from stage 2 of H&Y. This study is the first to describe functionality in PD using WHODAS 2.0 across severity stages controlling for key demographic factors. Findings highlight that WHODAS captures functional limitations not identified by symptom-focused scales such as MDS-UPDRS. Incorporating WHODAS into routine assessment may improve patient-centered care by informing interventions targeting functional limitations from early disease stages. HighlightsWHODAS 2.0 captures functionality domains not assessed by MDS-UPDRS. Functional decline in mobility, self-care, and household tasks starts at early PD stages. Participation, cognition, and interpersonal relationships decline from stage 2 onwards. Functionality decline is independent of age, sex, education, and socioeconomic status. WHODAS provides a biopsychosocial assessment essential for person-centered PD care.

IntroductionReliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinsons disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity. MethodsSixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinsons Disease Rating Scale - motor (UPDRS-III). ResultsThe speed of the key release was significantly slower in the PD compared to control cohorts (p <0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = 0.14, p = 0.43). ConclusionsThis validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that thirty seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.

ObjectiveAlthough Levodopa-carbidopa intestinal gel (LCIG) treatment has shown to be efficacious in motor and some non-motor symptoms (NMS), not all the patients with advanced Parkinsons disease (PD) are ideal candidates. To improve their selection analysis knowledge of prognostic factors is of great importance. We aimed to develop a novel machine learning model to predict the clinical outcomes of patients with advanced PD at 2 years under the LCIG therapy. MethodsThis was a longitudinal 24-month, observational study of 59 patients with advanced PD of a Greek multicenter registry under LCIG treatment from September 2019 to September 2021. Motor status was assessed with the Unified Parkinsons Disease Rating Scale (UPDRS) part III (off) and IV. NMS were assessed by the NMS Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS), the quality of life by PDQ-39 and severity by Hoehn &Yahr (HY). Multivariate linear regression, ARIMA, SARIMA, and Long Short-Term Memory-recurrent neural network (LSTM-RNN) models were used. ResultsDyskinesia duration and quality of life were significantly improved with LCIG (19% and 10% greater improvement for men than women, respectively). Multivariate linear regression models showed that UPDRS-III was decreased by 1.5 and 4.39 units per one unit of increase of the PDQ-39, UPDRS-IV indexes, respectively. Among all the time series models, the LSTM-RNN model predicts these clinical characteristics with highest accuracy (mean square error =0.0069) ConclusionsThe LSTM-RNN model predicts with highest accuracy sex dependent clinical outcomes of patients with advanced PD after two years of LCIG therapy.

BackgroundDisability in Parkinsons disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a previously validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Bradykinesia Tapping (DBT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 seconds), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps). ObjectiveTo develop and validate a new keyboard-tapping test to assess distal motor function in PD patients. MethodsThe DBT test was validated in 45 PD patients and 24 controls, alongside the BRAIN test. Test scores were compared between groups and correlated with MDS-UPDRS-III scores. 10 additional PD patients were recruited to assess the DBT test in monitoring motor fluctuations. ResultsAll three parameters discriminated between patients and controls, with KS20 performing best, yielding 75% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.87. Combination of both the DBT and BRAIN tests improved discrimination (AUC=0.91). KS20 and AT20 correlated with MDS-UPDRS-III (Pearsons r=-0.49, p<0.001 and r=0.54, p<0.001, respectively). The DBT test detected subtle changes in motor fluctuation states, which were not reflected clearly by MDS-UPDRS-III sub-scores. ConclusionThe DBT test is a user-friendly method of assessing distal motor dysfunction in PD, possibly permitting longitudinal monitoring of PD motor complications.

Parkinsons disease (PD), a progressive neurodegenerative disorder, manifests with motor and non-motor symptoms. Despite similar incidence, clinical care for Hispanic patients with PD is poor compared to white non-Hispanic individuals. As a result, their participation in PD research also does not reflect expected values. These disparities suggest an underutilization of quality healthcare, socio-economic disadvantage, stigma, and cultural differences. Using a community health worker pilot program, we trained 298 Promotores de Salud to reach, educate, and engage the Hispanic community in healthcare. Outcomes demonstrated improved knowledge of PD among Promotores, as well as increased access and utilization of educational resources.

BackgroundParkinsons disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step towards the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population. ObjectivesThis qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting. MethodsFocus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and clinical team. Data was analyzed using inductive thematic analysis. ResultsA total of twelve PwPs and thirteen CPs participated in seven focus groups. Participants were 52% female and 28% nonwhite; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explores the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD. ConclusionPD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility of ambulation protocols and an environment that accommodated their disability. Findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes.

The Movement Disorders Society clinical diagnostic criteria for Parkinsons disease (MDS-PD) allow highly sensitive and specific diagnosis of Parkinsons disease. However, their adoption has been limited due to lack of a clinical decision support (CDS) tool to support clinicians and researchers in systematically and accurately applying the MDS-PD criteria. We have developed and performed preliminary validation of a CDS platform for PD (CDS-PD) as a modular and extensible informatics platform with comprehensive functionalities for recording relevant patient information. We have performed real-time application of diagnostic algorithm of the MDS-PD criteria. The CDS-PD platform shows high concordance with application of the MDS-PD criteria by experienced movement disorders neurologists for established PD (disease duration [&ge;]5 years). The CDS-PD platform is a step towards realizing the standardized electronic implementation of the MDS-PD criteria for PD patient care and clinical trials at point-of-care. The CDS-PD platform can be accessed after registration at weblink https://www.cdspd.org.

ImportanceIf history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS. ObservationsWe identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinsons disease patients and for those with motor fluctuations and dyskinesias. Conclusions and RelevanceDespite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.

BackgroundPatients in late-stage Parkinsons disease (PDLS) are caregiver dependent, have low quality of life, and higher health care costs. ObjectiveTo estimate the prevalence of PDLS patients in the current United States (US) health care system. MethodsWe downloaded the 2010-2022 data from the TriNetX Diamond claims network that consists of 92 USA health care sites. PD was identified using standard diagnosis codes, and PDLS was identified by the usage of wheelchair dependence, personal care assistance and/or presence of diagnoses of dementia. Age of PDLS identification, and survival information are obtained and stratified by demographic and the disability subgroups. ResultsWe identified 1,031,377 PD patients in the TriNetX database. Of these, 18.8% fit our definition of PDLS (n=194,297), and 10.2% met two or more late-stage criteria. Among all PDLS, the mean age of PDLS identification was 78.1 ({+/-}7.7), and 49% were already reported as deceased. PDLS patients were predominantly male (58.5%), with similar distribution across PDLS subgroups. The majority did not have race (71%) or ethnicity (69%) information, but for the available information, >90% (n=53,162) were white, 8.2% (n=5,121) Hispanic/Latino, 7.8% (n=4,557) black, and <0.01% (n=408) Asian. Of the PDLS cohort, 71.6% identified with dementia, 12.9% had personal care assistance, and 4.8% were wheelchair bound. ConclusionsLate-stage patients are a significant part of PD landscape in the current US healthcare system, and largely missed by traditional motor-based disability staging. It is imperative to include this population as a clinical, social, and research priority.

ObjectiveTo explore the utility of using patient reported emergence of new symptoms (ES) as an outcome measure during the early phase of the disease. MethodsWe analyzed data from MDS-UPDRS Part IB and Part II from the Safety, Tolerability, and Efficacy Assessment of Isradipine for PD (STEADY-PD3) study, with at least one annual follow-up over two years. We divided the sample into categories of follow-up visit (between 0 and 12-months, and 13 and 24-months) and the number of ES for each part of the scale between participants who started symptomatic treatment and those who did not (STx-yes/no). We assessed ES differences between participants STx in each follow-up visit using Mann-Whitney U test, and the Kaplan-Meier analyses. ResultsOf 331 participants observed for months 0 to 12, 288 (87%) developed ES, and 182 (55%) started STx. For Part IB, the median number of ES did not significantly differ between the STx groups (Z=-0.86, p = 0.39), while for Part 2, the number of ES was significantly higher for the STx-yes group (Z=-2.38, p=0.02). Of 148 participants who continued to be observed for months 13 to 24, 114 (77%) developed ES, and 62 (42%) started STx. For Part IB, the median number of ES did not significantly differ between the STx groups (Z=-0.33, p = 0.74), while for Part 2, the number of ES was significantly higher for the STx-yes group (Z=-2.25, p=0.02). ConclusionsAssessing ES among patient-reported experiences of daily living may provide a useful marker for tracking PD progression.

IntroductionParkinsons disease (PD) causes significant impairment due to both motor and non-motor symptoms, which severely impact patients health-related quality of life (HRQoL) and increase caregiver burden. Given the rising prevalence of PD in an aging population, particularly in Germany, the need for innovative and resource-efficient healthcare approaches is paramount. The complexity of PD symptoms and the necessity for individualised, multidisciplinary and digital health technology-based care are widely acknowledged; however, access to specialist care remains limited, particularly in rural areas. Current healthcare systems are frequently ill-equipped to deliver timely, personalised interventions. In response to these challenges, the ParkProReakt project aims to enhance PD care through a proactive, technology-enabled, multidisciplinary approach designed to improve patient HRQoL and alleviate caregiver burden. Methods and analysisA randomised controlled trial will assess the efficacy and cost-effectiveness of ParkProReakt - a proactive, multidisciplinary, digitally supported care model for community-dwelling people with Parkinsons disease (PwPD) - compared with standard care. We will recruit a total of 292 PwPD and their informal caregivers living in two diverse regions in Germany. The primary outcome measure will be patients HRQoL as measured by the PDQ-39, obtained at baseline, monthly and at completion of participation. Secondary outcomes comprise patients subjective wellbeing, incidence or change of long-term care needs, global cognition and disease progression, utilisation of health care services including hospitalisations, caregiver burden and health care costs. Statistical analysis will include t-tests for HRQoL changes, GLM for confounders, and multilevel models for centre effects. Secondary outcomes and cost-effectiveness (ICER) will be analysed similarly, using R and SPSS. Ethics and disseminationThe study protocol has been approved by the Ethics Committees of the Medical Associations of Hesse and Hamburg. The results of our study will be reported to the funding body and disseminated through scientific publications and presentations at national and international conferences. Registration detailsThis study was registered with the German Registry for Clinical Studies (DRKS) in both German and English - number: DRKS00031092. What is already known on this topicParkinsons disease imposes severe motor and non-motor challenges on patients, impacting their quality of life and caregiver well-being. The complexity of symptoms necessitates individualized, multidisciplinary, and digital health-based approaches to care. Despite a recognized need for proactive, scalable interventions in Parkinsons disease care, existing health systems have limited capacity for implementing these comprehensive, resource-efficient models effectively. What this study addsThis study introduces a novel, proactive, technology-based, patient-centered model of care for people with Parkinsons disease, integrating wearable technology and an app to improve patient health-related quality of life. It rigorously assesses this models effectiveness and cost-efficiency in Germany. How this study might affect research, practice or policyThe studys findings could inform policy on proactive digital care for aging populations, improve Parkinsons disease care accessibility, and offer a framework for chronic disease management using patient-centered, cost-effective, and multidisciplinary approaches.

Parkinsons disease (PD) is characterized by the progressive dopaminergic neuron degeneration, resulting in striatal dopamine deficiency. Mitochondrial dysfunction and oxidative stress are associated with PD pathogenesis. Physical activity (PA) has been shown to ameliorate neurological impairments and to impede age-related neuronal loss. In addition, skin fibroblasts have been identified as surrogate indicators of pathogenic processes correlating with clinical measures. The PARKEX study aims to compare the effects of two different PA programs, analyzing the impact on mitochondrial function in patients skin fibroblasts as biomarkers for disease status and metabolic improvement. Early-stage PD patients (n=24, H&Y stage I to III) will be randomized into three age- and sex-matched groups. Group 1 (n=8) will undergo basic physical training (BPT) emphasizing strength and resistance. Group 2 (n=8) will undergo BPT combined with functional exercises (BPTFE), targeting the sensorimotor pathways that are most affected in PD (proprioception-balance-coordination) together with cognitive and motor training (Dual task training). Group 3 (n=8) will serve as control (sedentary group; Sed). Participants will perform three sessions per week for 12 weeks. Assessment of motor function, quality of life, sleep quality, cognitive aspects and humor will be conducted pre- and post-intervention. Patient skin fibroblasts will be collected before and after the intervention and characterized in terms of metabolic remodeling and mitochondrial bioenergetics. Ethical approval has been given to commence this study. This trial is registered at clinicaltrials.gov (NCT05963425)

ObjectiveThe aim of this study was to perform a quantitative analysis to evaluate the efficacy of cognitive behavioral therapy (CBT) on non-motor symptoms and its impact on quality of life (QOL) in Parkinsons disease (PD). MethodsWe searched for randomized controlled trials in three electronic databases. Twelve studies, including 358 patients with PD, met the inclusion criteria. We determined the pooled efficacy by standard mean differences and 95% confidence intervals, using I2 to reveal heterogeneity. ResultsThe result showed CBT had a significant effect on depression [-0.94 (95% CI, -1.25 to -0.64, P < 0.001)] and anxiety [-0.78 (95% CI, -1.05 to -0.50, P < 0.001)]. Moderate effect sizes were noted with stress [-0.60 (95% CI, -1.06 to -0.14, P = 0.01)] and sleep disorders [-0.44 (95% CI, -0.74 to -0.15, P = 0.003)]. There was no evident impact of CBT on fatigue or QOL. We found an intervention period > 8 weeks was advantageous compared with < 8 weeks, and CBT intervention was more effective than CBT developmental therapy. ConclusionWe found that CBT in patients with PD was an efficacious therapy for some non-motor symptoms in PD, but not efficacious for fatigue and QOL. These results suggest that CBT results in significant improvement in PD and should be used as a conventional clinical intervention.