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Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. Methods: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. Results: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. Conclusion: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD. [ABSTRACT FROM AUTHOR]

Objective: The objective was to determine the prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease patients in movement disorders outpatient clinics. Methods: We enrolled all consecutive PD patients who visited our movement disorders outpatient clinics between January and December 2023; and agreed to participate in the study. In addition to the evaluation of demographic and clinical features, clinical scales, including the MDS-UPDRS, NMSS, and FOOGQ, were performed. Results: Overall, we enrolled 163 PD subjects with a mean age of 63.9 ± 10.4 (F/M = 27/136). The disease duration was 3.5 (20) y [median (range)]. The median score of the NMSS was 41 points. The NMSs burden levels were severe in 25.2%, and very severe in 25.2% of the subjects. The subitems with the highest scores were sleep/fatigue, mood/cognition, urinary, and miscellaneous. The analyses within the patient group with newly diagnosed PD also revealed high NMSS scores. Comparisons of the NMSS between distinct PD stages revealed greater NMSS scores in the severe stage than in the mild stage (p = 0.001). Correlation analyses between the clinical scores and the NMSS scores revealed positive correlations between the NMSS scores and the scores on all the clinical scales including the MDS-UPDRS 1–4, and FOGQ. Conclusion: We reported the first data regarding the NMS burden in PD patients from Turkey. We found a high prevalence and severity of various domains of NMSs, most of which were sleep/fatigue, mood/cognition, urinary, and miscellaneous. More than half of the patients had severe to very severe NMS burden. Although NMSs were more common severe-stage disease, they were also prevalent in the subgroup with newly diagnosed patients. [ABSTRACT FROM AUTHOR]

Objective: Multiple system atrophy (MSA) is commonly associated with rapid eye movement sleep behavior disorder (RBD). Research on the prevalence of RBD in MSA and its effects on MSA patients has yielded inconsistent results. Currently, there is only one meta-analysis discussing the prevalence of RBD in MSA, but no meta-analysis discussing the impact of RBD on MSA. Methods: A systematic review and meta-analysis was conducted by searching studies related to MSA and RBD in PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate prevalence of RBD, odds ratio (OR), weighted mean differences (WMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic. Results: The prevalence of polysomnography confirmed-RBD in MSA was 79.9% (95% CI, 68.8-89.3%) in a pooled sample of 598 subjects. Patients with MSA who had RBD were notably younger at examination than those without RBD (WMD -3.26 years, 95% CI -4.99 to -1.53), and the age of disease onset in MSA patients with RBD was significantly lower than in those without RBD (WMD -3.27, 95% CI -5.06 to -1.48). Additionally, RBD was more common among male patients with MSA compared to female patients (OR 2.11, 95% CI 1.31 to 3.39). MSA patients with RBD also exhibited significantly higher Unified Multiple System Atrophy Rating Scale (UMSARS) I and IV scores than those without RBD (WMD 2.99, 95% CI 0.10 to 4.88, and WMD 0.23, 95% CI 0.03 to 0.43). Conclusion: The prevalence of polysomnography-confirmed RBD in MSA is 79.9%. The prevalence in Asian population was lower than in Europe and America, which might be related to an underestimation in Asian populations. Additionally, patients with MSA and RBD tend to be younger at examination, have an earlier age of onset, and exhibit more severe disease manifestations compared to MSA patients without RBD. [ABSTRACT FROM AUTHOR]

Background: Parkinson’s disease is a progressive neurodegenerative disease characterized by clinical motor signs and non-motor symptoms that severely impact quality of life. There is an urgent need for therapies that might slow, halt or even reverse the progression of existing symptoms or delay the onset of new symptoms. Photobiomodulation is a therapy that has shown potential to alleviate some symptoms of Parkinson’s disease in animal studies and in small clinical trials. Objective: To assess long-term effectiveness of photobiomodulation therapy in a cohort of Parkinson’s disease individuals after five years of continuing therapy. Methods: Eight participants of the initial 12 in a previously published study agreed to be reassessed after five years. Seven of these participants had continued home-based, self-applied photobiomodulation therapy three times per week for five years. One participant had discontinued treatment after one year. Participants were assessed for a range of clinical motor signs, including MDS-UPDRS-III, measures of mobility and balance. Cognition was assessed objectively, and quality of life and sleep quality were assessed using self-reported questionnaires. A Wilcoxon Signed Ranks test was used to evaluate change in outcome measures between baseline (before treatment) and after five years, with the alpha value set to 0.05. Results: Of the seven participants who had continued photobiomodulation therapy, one had a preliminary diagnosis of multisystem atrophy and was excluded from the group analysis. For the remaining six participants, there was a significant improvement in walk speed, stride length, timed up-and-go tests, tests of dynamic balance, and cognition compared to baseline and nonsignificant improvements in all other measures, apart from MDS-UPDRS-III, which was unchanged and one measure of static balance (single leg stance, standing on the unaffected leg with eyes open) which declined. Five of six participants either improved or showed no decline in MDS-UPDRS-III score and most participants showed improvement or no decline in all other outcome measures. No adverse effects of the photobiomodulation therapy were reported. Conclusions: This study provides a signal that photobiomodulation therapy might safely reduce important clinical motor signs and non-motor symptoms in some Parkinson’s disease patients, with improvements maintained over several years. Home-based photobiomodulation therapy has the potential to complement standard therapies to manage symptoms and potentially delay Parkinson’s symptom progression. Trial registration: Australian New Zealand Clinical Trials Registry, registration number ACTRN12618000038291p, registered on 12/01/2018. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion The cardinal motor symptoms of Parkinson's disease (PD) include rigidity, bradykinesia, and rest tremor. Rigidity and bradykinesia correlate with contralateral nigrostriatal degeneration and striatal dopamine deficit, but association between striatal dopamine function and rest tremor has remained unclear.The aim of this study was to investigate the possible link between dopamine function and rest tremor using Parkinson's Progression Markers Initiative dataset, the largest prospective neuroimaging cohort of patients with PD.Clinical, [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane ([123I]FP‐CIT) single photon emission computed tomography (SPECT), and structural magnetic resonance imaging data from 354 early PD patients and 166 healthy controls were included in this study. We employed a novel approach allowing nonlinear registration of individual scans accurately to a standard space and voxelwise analyses of the association between motor symptoms and striatal dopamine transporter (DAT) binding.Severity of both rigidity and bradykinesia was negatively associated with contralateral striatal DAT binding (PFWE < 0.05 [FWE, family‐wise error corrected]). However, rest tremor amplitude was positively associated with increased ipsilateral DAT binding (PFWE < 0.05). The association between rest tremor and binding remained the same controlling for Hoehn & Yahr stage, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III score, bradykinesia–rigidity score, or motor phenotype. The association between rest tremor and binding was independent of bradykinesia‐rigidity and replicated using 2‐year follow‐up data (PFWE < 0.05).In agreement with the existing literature, we did not find a consistent association between rest tremor and contralateral dopamine defect. However, our results demonstrate a link between rest tremor and increased or less decreased ipsilateral DAT binding. Our findings provide novel information about the association between dopaminergic function and parkinsonian rest tremor. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: Sleep-related breathing disorder (SRBD) is a prevalent non-motor symptom in multiple system atrophy (MSA). However, the reported prevalence of SRBD in MSA from different studies has shown inconsistency. Additionally, only one study has examined the impact of SRBD on both motor and nonmotor symptoms in MSA. Methods: Cross-sectional study of 66 patients with probable MSA from China. SRBD was ascertained with polysomnography (PSG). All the MSA individuals were assessed using the Epworth Sleepiness Scale (ESS), Unified Multiple-System Atrophy Rating Scale (UMSARS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), the Mini-mental State Examination (MMSE), Non-Motor Symptoms Scale (NMSS), and Pittsburgh Sleep Quality Index (PSQI). Moreover, a meta-analysis was conducted by searching studies related to MSA and SRBD in PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate prevalence of SBRD with 95% confidence intervals (CI). Results: Our study included 66 patients with MSA, 52 of whom had a diagnosis of SRBD (78.8%). There were no significant differences between the MSA with SRBD and without SRBD groups on the age, sex, disease onset, disease duration, UMSARS I, II, and IV, the NMSS, the HAMA, HAMD, the ESS the FSS, the MMSE, and the PSQI scales. However, MSA patients with SRBD having a significant higher obstructive apnea index and percentage of snoring during sleep than MSA patients without SRBD [10.0 (4.1-10.6) vs. 0.1 (0-0.3), and 8.3 (5.1-12.2) vs. 4.2 (0-7.5)]. Also, between the two groups, the mean and minimum oxygen concentrations during sleep were lower in MSA patients with SRBD than in those without SRBD [93.7 (93-95) vs. 95.5 (95.8-97), p = 0.001] and [83.9 (81.2-89.0) vs. 90.3 (89.8-93.3), p = 0.000]. The primary search strategy identified 701 articles, with 10 meeting the inclusion criteria. The overall prevalence of SRBD in a combined sample of 295 MSA patients was found to be 60.5% (95% CI, 43.2-76.5%). Further analysis revealed that the prevalence of SRBD in MSA patients in Asia was 79.2% (95% CI, 54.7-96.3%), which was higher than that in Europe (41.6, 95% CI, 32-51.5%). Conclusion: The study found a prevalence of 78.8% of SRBD in MSA patients, with a notably higher prevalence in Asia compared to Europe. The majority of SRBD cases in MSA were attributed to obstructive apnea. Furthermore, the presence of SRBD did not show a significant impact on the motor and nonmotor symptoms of MSA patients. [ABSTRACT FROM AUTHOR]

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations, leading to mitochondrial dysfunction, are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control. [ABSTRACT FROM AUTHOR]

Background/Objectives: A family history of Parkinson's disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients' PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity. [ABSTRACT FROM AUTHOR]

Abstract Background Parkinson’s disease is a progressive neurodegenerative disease characterized by clinical motor signs and non-motor symptoms that severely impact quality of life. There is an urgent need for therapies that might slow, halt or even reverse the progression of existing symptoms or delay the onset of new symptoms. Photobiomodulation is a therapy that has shown potential to alleviate some symptoms of Parkinson’s disease in animal studies and in small clinical trials. Objective To assess long-term effectiveness of photobiomodulation therapy in a cohort of Parkinson’s disease individuals after five years of continuing therapy. Methods Eight participants of the initial 12 in a previously published study agreed to be reassessed after five years. Seven of these participants had continued home-based, self-applied photobiomodulation therapy three times per week for five years. One participant had discontinued treatment after one year. Participants were assessed for a range of clinical motor signs, including MDS-UPDRS-III, measures of mobility and balance. Cognition was assessed objectively, and quality of life and sleep quality were assessed using self-reported questionnaires. A Wilcoxon Signed Ranks test was used to evaluate change in outcome measures between baseline (before treatment) and after five years, with the alpha value set to 0.05. Results Of the seven participants who had continued photobiomodulation therapy, one had a preliminary diagnosis of multisystem atrophy and was excluded from the group analysis. For the remaining six participants, there was a significant improvement in walk speed, stride length, timed up-and-go tests, tests of dynamic balance, and cognition compared to baseline and nonsignificant improvements in all other measures, apart from MDS-UPDRS-III, which was unchanged and one measure of static balance (single leg stance, standing on the unaffected leg with eyes open) which declined. Five of six participants either improved or showed no decline in MDS-UPDRS-III score and most participants showed improvement or no decline in all other outcome measures. No adverse effects of the photobiomodulation therapy were reported. Conclusions This study provides a signal that photobiomodulation therapy might safely reduce important clinical motor signs and non-motor symptoms in some Parkinson’s disease patients, with improvements maintained over several years. Home-based photobiomodulation therapy has the potential to complement standard therapies to manage symptoms and potentially delay Parkinson’s symptom progression. Trial registration Australian New Zealand Clinical Trials Registry, registration number ACTRN12618000038291p, registered on 12/01/2018.

Background: Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by dopamine depletion and severe motor impairments. Preladenant, an adenosine A2 receptor antagonist, is an investigational treatment for PD. This systematic review and meta-analysis aimed to critically evaluate the efficacy of Preladenant in improving motor symptoms in patients with PD. Methods: A comprehensive literature search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to March 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing Preladenant with placebo in PD patients were included. The primary outcome was the change in daily ON time without troublesome dyskinesia. Secondary outcomes included the change in daily OFF time and adverse events. The risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Four RCTs with a total of 2097 PD patients were included. Pooled analysis showed that Preladenant could generally increase daily ON time (pooled effect 0.15 and 95 % CI: −0.19–0.48) and reduce daily OFF time (pooled effect −0.04 and 95 % CI: −0.43–0.36) compared to placebo, however it was not significant. The included studies had moderate to high heterogeneity. No significant differences in adverse events were observed between Preladenant and placebo. Conclusion: This meta-analysis suggests that Preladenant may improve motor fluctuations in PD patients by increasing ON time and reducing OFF time. However, the high heterogeneity among studies warrants further large-scale, high-quality RCTs to confirm these findings and establish the long-term safety and efficacy of Preladenant in PD management.

Abstract Background Repetitive Transcranial Magnetic Stimulation (rTMS) and EEG-guided neurofeedback techniques can reduce motor symptoms in Parkinson’s disease (PD). However, the effects of their combination are unknown. Our objective was to determine the immediate and short-term effects on motor and non-motor symptoms, and neurophysiological measures, of rTMS and EEG-guided neurofeedback, alone or combined, compared to no intervention, in people with PD. Methods A randomized, single-blinded controlled trial with 4 arms was conducted. Group A received eight bilateral, high-frequency (10 Hz) rTMS sessions over the Primary Motor Cortices; Group B received eight 30-minute EEG-guided neurofeedback sessions focused on reducing average bilateral alpha and beta bands; Group C received a combination of A and B; Group D did not receive any therapy. The primary outcome measure was the UPDRS-III at post-intervention and two weeks later. Secondary outcomes were functional mobility, limits of stability, depression, health-related quality-of-life and cortical silent periods. Treatment effects were obtained by longitudinal analysis of covariance mixed-effects models. Results Forty people with PD participated (27 males, age = 63 ± 8.26 years, baseline UPDRS-III = 15.63 ± 6.99 points, H&Y = 1–3). Group C showed the largest effect on motor symptoms, health-related quality-of-life and cortical silent periods, followed by Group A and Group B. Negligible differences between Groups A-C and Group D for functional mobility or limits of stability were found. Conclusions The combination of rTMS and EEG-guided neurofeedback diminished overall motor symptoms and increased quality-of-life, but this was not reflected by changes in functional mobility, postural stability or depression levels. Trial registration NCT04017481.

Abstract To investigate the association between COVID-19 and Parkinson’s disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (β = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility.

Background Objective Methods Results Conclusion Invasive deep brain stimulation (DBS) has been shown to be effective in treating patients with Parkinson's disease (PD), yet its clinical use is limited to patients at the advanced stage of the disease. Transcranial temporal interference stimulation (tTIS) may be a novel nonneurosurgical and safer alternative, yet its therapeutic potential remains unexplored.This pilot study aims to examine the feasibility and safety of tTIS targeting the right globus pallidus internus (GPi) for motor symptoms in patients with PD.Twelve participants with mild PD completed this randomized, double‐blind, and sham‐controlled experiment. Each of them received either 20‐minute or sham tTIS of the right GPi. Before and immediately after the stimulation, participants completed the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS‐III) in the “medication‐on” state to assess the motor symptoms. The blinding efficacy and side effects were also assessed.tTIS was well tolerated by participants, with only mild, transient adverse effects reported. tTIS significantly reduced MDS‐UPDRS‐III scores by 6.64 points (14.7%), particularly in bradykinesia (23.5%) and tremor (15.3%). The left side showed more significant alleviation in motor symptoms, particularly bradykinesia, compared to the right side. Participants with severer bradykinesia and tremor before stimulation experienced greater improvement after tTIS.This pilot study suggests that the tTIS, as a novel noninvasive DBS approach, is feasible and safe for alleviating motor symptoms in mild PD, especially bradykinesia and tremor. Future larger‐scale and more definitive studies are needed to confirm the benefits. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Parkinson's Disease is a neurodegenerative disorder manifesting itself as a hypokinetic movement impairment with postural instability and gait disturbance. In case of failure and/or limited response, deep brain stimulation has been established as an alternative and effective treatment modality. However, a subset of PD patients with gait impairment represents a therapeutic challenge. A systematic review (2000–2023) was performed using PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases to determine the efficacy, stimulation waveform/parameters, spine level, and outcome measures of spinal cord stimulation using different waveforms in PD patients with and without chronic pain. Spinal cord stimulation responsiveness was assessed within the pre-defined follow-up period in three groups (short-term follow-up = 0–3 months; intermediate follow-up = 3–12 months; and long-term follow-up = more than 12 months). In addition, we briefly outline alternative neurostimulation therapies and the most recent developments in closed-loop spinal cord stimulation relevant to PD. In summary, 18 publications and 70 patients from uncontrolled observational trials were included, with low-quality evidence and conflicting findings. First and foremost, the currently available data do not support the use of spinal cord stimulation to treat PD-related gait disorders but have confirmed its usefulness for PD-associated chronic pain. [ABSTRACT FROM AUTHOR]

(1) Background: Previous studies, mostly performed in European centers, have shown that in-patient multimodal intensive rehabilitation treatments lasting for two to four weeks can improve both motor and non-motor symptoms of Parkinson's disease (PD) with long-lasting effects. Here, we ascertain the effects of a similar in-patient program in a U.S. center with a retrospective study in a cohort of 153 patients in the moderately advanced stage of PD. (2) Methods: We compared indices of motor and non-motor functions before and immediately after such treatment and investigated the possible differences between men and women. We used the available records of the Beck Depression Inventory, PDQ39, PD Sleep Scale, Timed Up and Go, Vocal Volume, Voice Handicap, and total UPDRS scores. (3) Results: We found that at the end of treatment, which lasted an average of 14 days, all outcome measures significantly improved independently of sex. (4) Conclusions: These results confirm the previous findings with a similar in-patient approach in European centers. They further suggest that this in-patient treatment is a care model that is feasible in U.S. centers and can provide a more immediate benefit to the motor function and quality of life of patients with moderately advanced PD. [ABSTRACT FROM AUTHOR]

Background: The World Health Organisation (WHO) reports that morbidity and mortality due to Parkinson's disease (PD) are increasing faster than for other neurodegenerative conditions. People with Parkinson's (PwP) present with a variety of motor symptoms, such as tremor, bradykinesia, and rigidity. Freezing of gait (FoG) is a significant motor symptom that manifests as temporary episodes of inability to move one's feet, despite the intention to walk. Aims: This study examined the impact of FoG on quality of life (QoL) within an Irish cohort of PwP, from the perspectives of both PwP and their carers, using validated questionnaires that had been adapted for online use. Methods: PwP and their carers were recruited by outreach to the Irish Parkinson's Community. Anonymous online questionnaires were distributed, which combined a demographic survey with several clinically validated surveys, including Freezing of Gait Questionnaire (FoG-Q), Parkinson's Disease Questionnaire 8 (PDQ-8), and Parkinson's Disease Carer Questionnaire (PDQ-C). Results: There was a strong correlation (p < 0.001) between severity of FoG and lower QoL among PwP. Significant correlation was also found between FoG severity and several motor symptoms, such as postural instability and difficulty with balance, and non-motor symptoms, such as cognitive changes and pain/discomfort. FoG severity correlated with disease progression. Significant correlation was also found between FoG and symptoms, as assessed from the perspective of the patients' carers. Conclusions: This study shows that FoG is a significant detriment to the QoL of PwP, from the perspectives of patients and carers. This method of assessing FoG and QoL using online questionnaires has potential to enhance the reach and flexibility of this type of research. These findings will inform future studies on larger cohorts and highlight unmet clinical needs in PwP. [ABSTRACT FROM AUTHOR]

To investigate the association between COVID-19 and Parkinson's disease (PD) via a single-center study and a Mendelian randomization (MR) study. A questionnaire-based survey was conducted among PD patients at a single center from December 7, 2022, to March 10, 2023. Logistic regression analysis was performed to identify the infection-related risk factors. Subsequently, bidirectional two-sample Mendelian randomization was employed to explore the association between COVID-19 and PD. In the cross-sectional analysis, it was found that the prevalence of COVID-19 infection in PD patients was 65.7%. Forty-eight (35.3%) PD patients experienced exacerbation of motor symptoms following COVID-19 infection. Long PD disease duration (≥ 10 years) (OR: 3.327, P = 0.045) and long time since last vaccination (> 12 m) (OR: 4.916, P = 0.035) were identified as significant risk factors related to infection. The MR analysis results supported that PD increases the COVID-19 susceptibility (β = 0.081, OR = 1.084, P = 0.006). However, the MR analysis showed that PD did not increases the COVID-19 severity and hospitalization, and no significant association of COVID-19 on PD was observed. The findings from this cross-sectional study suggest that individuals with PD may experience worsened motor symptoms following COVID-19 infection. Long disease duration (≥10 years) and long time since last vaccination (> 12 m) are identified as important risk factors for infection in these patients. Furthermore, our MR study provides evidence supporting an association between PD and COVID-19 susceptibility. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of home‐based exercise in Parkinson's disease (PD) patients. Design: A network meta‐analysis of randomized controlled trials. Methods: This study systematically searched PubMed, MEDLINE, Embase, Cochrane library and Web of Science. The quality of the literature was assessed using the Cochrane Risk of Bias 2.0 criteria. The data were pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). Results: Thirty studies involving 2264 PD patients were included. Meta‐analysis results showed that home‐based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD: −.28, 95% Crl [−.43; −.14]), improving quality of life (SMD =.15 [.03,.26]), walking speed (SMD =.30 [.04,.56]), balance ability (SMD =.18 [.04,.33]; p <.0001) and finger dexterity (SMD =.28 [.10,.46]). Mixed exercise (Mix) had better effects on improving motor symptoms and quality of life. In addition, the results of dose analysis showed that only mixed exercise exceeding 850 METs‐min per week and more than 18 weeks can significantly alleviate the overall motor symptoms of PD patients. Conclusion: Home‐based exercise was an effective form of therapy for alleviating motor symptoms. In addition, Mix appeared to be more suitable for PD patients engaging in home‐based exercise. Existing evidence suggested that significant therapeutic effects were achieved with a Mix, with a weekly exercise volume exceeding 850 METs and a duration of more than 18 weeks. Relevance to Clinical Practice: Home‐based exercise had a small effect in relieving overall motor symptoms in PD patients, improving quality of life, walking speed, balance ability and finger dexterity. In terms of exercise dosage, we recommend the exercise period is no less than 18 weeks and the dose per is no less than 850 METs‐min. No Patient or Public Contribution. [ABSTRACT FROM AUTHOR]

Background: Remote programming (RP) is an emerging technology that enables the adjustment of implantable pulse generators (IPGs) via the Internet for people with Parkinson's disease (PwPD) who have undergone deep brain stimulation (DBS). Previous studies have not comprehensively explored the effectiveness of RP in managing motor symptoms, often omitting assessments such as the rigidity and retropulsion tests during the follow-up. This study evaluates the comprehensive improvements in motor performance and the potential cost benefits of RP for PwPD with DBS. Methods: A retrospective analysis was conducted on two groups of patients--those who received RP and those who received standard programming (SP). Clinical outcomes including motor improvement, quality of life, and daily levodopa dosage were compared between the groups during a 12 (± 3)-month in-clinic follow-up. Results: A total of 44 patients were included in the study, with 18 in the RP group and 26 in the SP group. No significant differences were observed in the frequency of programming sessions or clinical outcomes between the groups (p > 0.05). However, the RP group experienced significantly lower costs per programming session than the SP group (p < 0.05), despite patients in the former group living further from our center (p < 0.05). Conclusions: Our findings suggest that RP could significantly reduce the costs of programming for PwPD with DBS, especially without compromising the effectiveness of treatment across all motor symptoms in the short term. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents. [ABSTRACT FROM AUTHOR]

Background and Objective: The Levodopa in EArly Parkinson's disease study showed no effect of earlier versus later levodopa initiation on Parkinson's disease (PD) progression over 80 weeks. We now report the effects over 5 years. Methods: The Levodopa in EArly Parkinson's disease study randomly assigned patients to levodopa/carbidopa 300/75 mg daily for 80 weeks (early start) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed start). Follow‐up visits were performed 3 and 5 years after baseline. We assessed the between‐group differences in terms of square root transformed total Unified Parkinson's Disease Rating Scale score at 3 and 5 years with linear regression. We compared the prevalence of dyskinesia, prevalence of wearing off, and the levodopa equivalent daily dose. Results: A total of 321 patients completed the 5‐year visit. The adjusted square root transformed total Unified Parkinson's Disease Rating Scale did not differ between treatment groups at 3 (estimated difference, 0.17; standard error, 0.13; P = 0.18) and 5 years (estimated difference, 0.24; standard error, 0.13; P = 0.07). At 5 years, 46 of 160 patients in the early‐start group and 62 of 161 patients in the delayed‐start group experienced dyskinesia (P = 0.06). The prevalence of wearing off and the levodopa equivalent daily dose were not significantly different between groups. Conclusions: We did not find a difference in disease progression or in prevalence of motor complications between patients with early PD starting treatment with a low dose of levodopa 40 weeks earlier versus 40 weeks later over the subsequent 5 years. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

As a neurologist who has followed up countless Parkinson's patients over the last 32 years of my fifty-year career; I denied diagnosing myself with Parkinson's disease (PD), although the seldom mild involuntary "twitches" that occurred in the thumb of my right hand over a two-year period, resembled Parkinson's disease tremor. However, when these involuntary contractions became persistent; considering its similarity to characteristic resting tremor in typical PD, the positive effect of dopaminergic medications, the development of levodopa-induced dyskinesias and other non-motor symptoms, it was clear that the PD diagnosis was accurate. This situation naturally caused me anxiety, and for a year and a half, I kept my diagnosis hidden from everyone except a few close relatives. However, with the encouragement of a psychiatrist friend, when I was able to share my condition with my loved ones, I felt a relative reduction in the burden I was carrying and consequently experienced emotional relief. I am still able to carry out my daily activities independently with a rather low dose of medication, and my PD symptoms do not attract noticeable attention. [ABSTRACT FROM AUTHOR]

Tai Chi is a traditional Chinese martial art characterized by maintaining postures and performing slow, fluid movements. This exercise involves actions like extending the knees and hips, shifting weight, flexing, rotating the trunk, and coordinating arm movements. All of this improves balance, motor coordination, and also mental stability. In this review, we explore the relationship between practicing Tai Chi and the improvement of physical abilities in individuals with Parkinson's Disease. We will also compare Tai Chi to other alternative methods for improving physical abilities.

Background: Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression. Objective: Determine the correlation between the time of dopaminergic replacement treatment initiation and the severity of clinical symptoms in PD, including motor and non-motor symptoms. Methods: PD patients were divided between 155 people who were diagnosed de novo and 165 PDpatients receiving dopamine replacement therapy. Basic patient characteristics included gender, age, age at onset, disease duration, and the time of dopaminergic replacement treatment initiation. We used MDS-UPDRS scores to evaluate the severity of motor symptoms and we also used the scale to assess the severity of non-motor symptoms such as cognition, mood, sleep, and quality of life. Results: The mean time between symptom onset and the initiation of drug treatment was 31.0 (22.5) months. After adjusting for age, sex, age at onset, and disease duration, we found that the MDS-Unified Parkinson's Disease Rating Scale (UPDRS)-III score increased faster in the de novo group with a similar disease duration (F = 8.7, p = 0.0034) than the treatment group. The cumulative incidence of progression to H-Y score 3 in de novo PD group over disease duration was 39.7% in 50months and 92.2% in 100 months, while in treated group such cumulative incidence was 15.5% in 50 months, 51.4% in 100 months and 81.5% in 150 months. The cumulative incidence of patients in the de novo PD group was higher than that in the treated group (p = 0.001), suggesting that untreated patients were more likely to progress to the advanced stages. Symptoms onset, the time between symptomonset and treatment initiation, age, sex, and disease duration explained 28.95% of the total variation in the MDS-UPDRS-III score for motor symptoms. In drug-naïve patients, the time between symptom onset and treatment initiation explained 20.1% of the total variation in the MDS-UPDRS-III score for motor symptoms (t = 6.15, p < 0.001). Conclusions: These data in our study showed that early dopaminergic replacement treatment have played a positive role in PD patients, while dopaminergic replacement delayed treatment might be detrimental to motor symptoms and non-motor state of PD patient. Recognizing early stage symptoms of PD and early diagnosis are of great significance to treatment. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) presents with motor symptoms that hinder physical activity. This study aimed to thoroughly investigate swallowing dysfunction in patients with PD using videofluoroscopy (VF) and the Movement Disorder Society (MDS)-Unified PD Rating Scale (UPDRS) sub-scores. Methods: This study was part of an intervention project to evaluate the effectiveness of cervical percutaneous interferential current stimulation in patients with Hoehn and Yahr stages 2–4 PD. Baseline data, including swallowing-related indicators such as VF, were obtained and compared to the MDS-UPDRS sub-scores including rigidity, tremor, postural instability/gait difficulty, and limb scores. Results: Twenty-seven patients were included in this study. In the VF analysis, laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecular residue, and pharyngeal residue were observed with remarkable frequency. The multivariate analysis revealed that the mean rigidity score of UPDRS was an independent and significantly correlated factor with laryngeal penetration/aspiration during the ingestion of 10 mL of water (odds ratio 1.294, 95% confidence interval 1.035–1.617; p = 0.024). Conclusion: This study revealed a correlation between muscle rigidity and laryngeal penetration or aspiration risk. The detailed comparative analysis of various individual PD symptoms and swallowing disorders was substantial, which enabled early detection of the risk of swallowing disorder and the implementation of appropriate measures. Trial registration number: jRCTs062220013. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a rare yet debilitating neurodegenerative disorder originating from an increase in CAG repeats within the HTT gene. Despite ongoing research, a curative treatment for HD remains elusive, with current therapeutic strategies primarily targeting symptom management. Among the spectrum of HD symptoms, motor impairments are often the most obvious and disabling. To standardize treatment regimens and enhance patient care and quality of life, global evidence-based Clinical Practice Guidelines (CPGs) have been published to reduce variations in care. The integration of these guidelines into clinical information systems could significantly improve physician adherence to them, thereby optimizing patient outcomes. This study aims to develop an openEHR template specifically designed to represent recommendations for managing Huntington's motor symptoms, contributing to standardized care delivery, and enabling the seamless exchange of treatment information among different healthcare providers involved in the management of HD. We assessed the International Guidelines for the Treatment of Huntington's Disease commissioned by the European Huntington's Disease Network (EHDN) and selected the most representative variables regarding the HD motor symptoms. The openEHR template development followed the methodological guidance of the openEHR data modeling approach ('odma'). A total of 101 data items were extracted from the guideline section related to motor symptoms. After the classification and merging of these data elements, six domain concepts were organized for the motor symptom's treatment of Huntington's disease. This study successfully developed an openEHR template for managing Huntington's disease motor symptoms. These advancements have the potential to enhance treatment outcomes and transform care delivery for Huntington's disease. [ABSTRACT FROM AUTHOR]

Background and objectives. The rising prevalence of sleep issues are a consequent societal problem, notably impacting individuals with Parkinson's disease (PD). This study aims to examine the differences in sleep quality between diagnosed patients and their counterparts, while also highlighting its effects on their symptoms and quality of life. Materials and methods. This study enrolled 37 PD subjects. Sleep quality, established via the Pittsburgh Sleep Quality Index (PSQI), was compared through a case control approach against 49 control subjects. PD symptomatology assessment was ensured via: Hoehn & Yahr (H&Y); Movement Disorder Society-Unified Parkinson's disease rating scale (MDS-UPDRS I-IV); Non-motor Symptom Scale (NMSS); Beck Depression Inventory (BDI); Montreal Cognitive Assessment (MOCA); Scale for Outcomes in Parkinson's disease - Psychosocial Functioning (SCOPA-PS); 39-Item Parkinson's Disease Questionnaire (PDQ-39). Results. Compared to their homologues, PD subjects were prone to worse subjective sleep quality (18.9% vs. 8.2%), sleep efficiency (13.5% vs. 4.1%), diurnal functionality (27% vs. 12.2%), sleep related breathing disorders (62.2% vs. 46.9%). The global PSQI positively correlates to H&Y staging ( rp = 0.443 p = 0.008 ), UPDRS-III ( rp = 0.369, p = 0.029 ), UPDRS-IV (rp= 0.412, p = 0.011 ) PD subjects with PSQI >5 registered higher UPDRS-III (p = 0.091), BDI (p = 0.928) SCOPA-PS (p = 0.051) PSQ15 correlates to PDQ-39 ( rp = 0.423, p = 0.01 ) and SCOPA-PS ( rp = 0.462 p = 0.004 ) . Conclusions. The study proved a clear correlation between altered sleep patterns and the clinical presentation of PD delineating the worsening of motor along to non-motor symptoms. In addition, the quality of life along to the psycho- social functioning of PD subjects is at risk in those manifesting sleep disturbances. Correspondingly, a greater interest should be applied in the establishment of prophylactic measures. [ABSTRACT FROM AUTHOR]

Wearable sensors could be beneficial for the continuous quantification of upper limb motor symptoms in people with Parkinson's disease (PD). This work evaluates the use of two inertial measurement units combined with supervised machine learning models to classify and predict a subset of MDS-UPDRS III subitems in PD. We attached the two compact wearable sensors on the dorsal part of each hand of 33 people with PD and 12 controls. Each participant performed six clinical movement tasks in parallel with an assessment of the MDS-UPDRS III. Random forest (RF) models were trained on the sensor data and motor scores. An overall accuracy of 94% was achieved in classifying the movement tasks. When employed for classifying the motor scores, the averaged area under the receiver operating characteristic values ranged from 68% to 92%. Motor scores were additionally predicted using an RF regression model. In a comparative analysis, trained support vector machine models outperformed the RF models for specific tasks. Furthermore, our results surpass the literature in certain cases. The methods developed in this work serve as a base for future studies, where home-based assessments of pharmacological effects on motor function could complement regular clinical assessments. [ABSTRACT FROM AUTHOR]

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD. [ABSTRACT FROM AUTHOR]

Around 10 million people worldwide have Parkinson's and in the UK the estimated figure is 153 000. The condition is characterised by motor symptoms including tremors, stiffness, slowness, balance problems and/or gait disorders, but people can develop a wide range of associated psychological and physical problems. Treatment for Parkinson's includes a combination of multidisciplinary input from specialists such as physiotherapy, speech and language therapy and occupational therapy, alongside the use of recognised medication regimens. Most first-line medication requires titration and is started at a low dose and increased gradually, to reduce the risk of side effects and to monitor response to treatment. Medications for Parkinson's are complex to manage, and many have side effects that could affect patient concordance. Any prescribing decisions should be discussed with the person with Parkinson's and their family members. There are a variety of medications available to manage motor and non-motor symptoms in Parkinson's, but this article will focus on levodopa, dopamine agonists, MAO-B inhibitors and catechol-O-methyltransferase inhibitors. [ABSTRACT FROM AUTHOR]

Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. Continuous DBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and globus pallidus (dual target DBS) in a prospective within-participant, clinical trial in six patients with Parkinson's disease (n = 6, 55–65 years, n = 2 females). Dual target cDBS was tested for Parkinson's disease symptom control annually over 2 years, measured by motor rating scales, on time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral aDBS using a novel distributed (off-implant) architecture. In the home setting, we collected tremor and dyskinesia scores as well as individualized β and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by Unified Parkinson's Disease Rating Scale (UPDRS) to a greater degree than either region alone (P < 0.05, linear mixed model) in the cohort. The amplitude of β-oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (P < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artefacts and demonstrated a correlation between STN β amplitude and DBS amplitude. Proportional plus integral control of aDBS reduced average power, while preserving UPDRS III scores in the clinic (P = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n = 3 , P > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of Parkinson's disease over DBS of either the STN or globus pallidus alone. When combined with proportional plus integral aDBS, stimulation power may be reduced, while preserving the increased benefit of dual target DBS. [ABSTRACT FROM AUTHOR]

Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e. bradykinesia) in Parkinson's disease. However, striatal dopamine loss fails to account for interindividual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that interindividual differences in clinical severity are determined by compensatory cortical mechanisms and not just by basal ganglia dysfunction. Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson's disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes that are hypothesized to reflect distinct routes of α-synuclein propagation: diffuse-malignant (n = 42), intermediate (n = 128) or mild motor-predominant (n = 150). Second, we used the scores of bradykinesia severity and cognitive performance across the entire sample as continuous measures. Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared with controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical scores. This indicates a limited role for striatal dysfunction in shaping interindividual differences in clinical severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and controls. Furthermore, increased parieto-premotor activity was related to lower bradykinesia severity and better cognitive performance, which points to a compensatory role. We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes interindividual variability in symptom severity in Parkinson's disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction. [ABSTRACT FROM AUTHOR]

Around 10 million people worldwide have Parkinson's disease and in the UK the estimated figure is 153000. The condition is characterised by motor symptoms including tremors, stiffness, slowness, balance problems and/or gait disorders, but sufferers can develop a wide range of associated psychological and physical problems. Treatment includes a combination of pharmacological and supportive physical therapies, supplied by a multidisciplinary team. As the condition progresses, medication regimens expand to include a combination of drug therapies. For those who do not benefit from pharmacological therapy deep brain stimulation surgery can be considered. Some people find that alternative therapies such as homeopathy, music and massage are useful additions to standard medical treatments. This article will give an overview of Parkinson's disease, including symptoms and diagnosis, and explore issues for consideration when prescribing common first-line Parkinson's medications. [ABSTRACT FROM AUTHOR]

Noninvasive stimulation of the nervous system is of growing interest in Parkinson's disease (PD) to slow-down motor decline and decrease medication and its side-effects. Repetitive transcranial magnetic stimulation (rTMS) used in PD to modulate the excitability of the primary motor cortex (M1) provided controversial results, in part because of interactions with medication. This warrants to administer rTMS in drug-free patients. Repetitive peripheral magnetic stimulation (rPMS of muscles) has not yet been tested in PD. Its influence on M1 plasticity (as tested by TMS, transcranial magnetic stimulation) and sensorimotor disorders in other health conditions makes it worth be explored in PD. Thus, rTMS and rPMS were tested in a drug-free woman (52 years old, PD-diagnosed 10 years ago) in four different rTMS + rPMS combinations (one week apart): sham-sham, real-real, real-sham, sham-real. rTMS was applied over M1 contralateral to the most impaired bodyside, and rPMS on muscles of the legs, trunk, and arms, bilaterally. M1 plasticity (TMS measures) and motor symptoms and function (clinical outcomes) were measured at different timepoints. The real-real session induced the largest motor improvements, with possible summation of effects between sessions, and maintenance at follow-up (80 days later). This was paralleled by changes of M1 facilitation and inhibition. This sheds a new light on the link between TMS measures of M1 plasticity and motor changes in PD and informs on the remaining potential for neuroplasticity and functional improvement after 10 years of PD with no antiparkinsonian drug. De novo patients with PD (drug-free) should be motivated to participate in future randomized clinical trials to further test the slow-down or delay of motor decline under noninvasive neurostimulation regimens, whatever the stage of the disease.

Background: In the medical and rehabilitative field, it is essential to employ tools such as evaluation scales and performance tests to assess the impact of Parkinson's disease on QoL of affected individuals. The Short Parkinson's Evaluation Scale (SPES) is a reliable and valid tool, applicable both in research and clinical practices, useful in assessing motor damage, activities of daily living, and motor complications in patients with Parkinson's disease. The aim of the study is to investigate validity and reliability of the Italian version of the SPES-SCOPA scale. Methods: Translation and cultural adaptation were performed. Included patients had diagnosis of Parkinson's disease, no concurrent pathologies, MiniMental test score above 2 and signed informed consent; they were recruited at the Department of Human Neurosciences in Sapienza University of Rome, from February 2023 to November 2023. Test-retest reliability was evaluated through Intraclass Correlation Coefficient (ICC), internal consistency was assessed using Cronbach's Alpha and construct validity using Pearson's correlation between SPES-SCOPA and the gold standard PDQ-39. Results: 101 patients were recruited. Inter-rater evaluation was conducted on 62 patients, while 39 underwent an intra-rater assessment. The analysis showed statistically significant data with a Cronbach's Alpha value of 0.89 for the entire scale; test-retest reliability results are statistically significant for all subscales. Correlation between PDQ-39 domains and SPES/SCOPA subscales were statistically significant for most measurements. Conclusion: This research shows that the Italian version of SPES-SCOPA scale has excellent psychometric properties.

Motor symptoms such as tremor and bradykinesia can develop concurrently in Parkinson’s disease; thus, the ideal home monitoring system should be capable of tracking symptoms continuously despite background noise from daily activities. The goal of this study is to demonstrate the feasibility of detecting symptom episodes in a free-living scenario, providing a higher level of interpretability to aid AI-powered decision-making. Machine learning models trained on wearable sensor data from scripted activities performed by participants in the lab and clinician ratings of the video recordings of these tasks identified tremor, bradykinesia, and dyskinesia in the supervised lab environment with a balanced accuracy of 83%, 75%, and 81%, respectively, when compared to the clinician ratings. The performance of the same models when evaluated on data from subjects performing unscripted activities unsupervised in their own homes achieved a balanced accuracy of 63%, 63%, and 67%, respectively, in comparison to self-assessment patient diaries, further highlighting their limitations. The ankle-worn sensor was found to be advantageous for the detection of dyskinesias but did not show an added benefit for tremor and bradykinesia detection here.

Abstract Background Faced with the lack of physical activity caused by mandatory home isolation during special periods and patients' inconvenience in carrying out professionally supervised exercise, many home-based exercise programs have been developed. This systematic review and meta-analysis aimed to examine the effects of home-based exercise on measures of motor symptoms, quality of life and functional performance in Parkinson's disease (PD) patients. Methods We performed a systematic review and meta-analysis, and searched PubMed, MEDLINE, Embase, Cochrane library, and Web of Science from their inception date to April 1, 2023. The quality of the literature was assessed using PEDro's quality scale. The data was pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). Results A total of 20 studies involving 1885 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD = -0.29 [-0.45, -0.13]; P

Objective: Parkinson's disease (PD) is marked not only by motor symptoms but also by neuropsychiatric manifestations, including demoralization, apathy, and depression. Understanding the clinical distribution and characteristics of these co-occurring symptoms is crucial for improving quality of life of PD patients. Methods: This study enrolled 195 Chinese PD patients from Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The study involved analyzing the clinical characteristics related to the simultaneous presence of demoralization, apathy, and depression in PD patients. Linear regression was employed to elucidate the linear trend between the quantity of negative neuropsychiatric symptoms and cognitive function, as well as motor symptoms and motor complications. SPSS mediation models were utilized to investigate whether the severity of cognitive function mediated the connection between multiple negative neuropsychiatric symptoms and motor symptoms. Results: Among PD patients, a notable 57.5% experience the presence of multiple concurrent negative neuropsychiatric symptoms. Our investigation unveiled a correlation where patients with more negative neuropsychiatric symptoms displayed heightened cognitive impairment (P=0.048) and more severe motor symptoms (P=0.024), following a linear trend with increasing symptom numbers. Additionally, cognitive impairment played a partial mediating role in the impact of multiple negative neuropsychiatric symptoms on motor symptoms (β=0.747; 95% bootstrap confidence interval: 0.195 to 1.532). Conclusions: The co-occurrence of these negative neuropsychiatric symptoms has the potential to worsen cognitive function and motor symptoms in PD patients. Moreover, cognitive impairment was identified as playing a partial mediating role in the relationship between multiple negative neuropsychiatric symptoms and motor symptoms. [ABSTRACT FROM AUTHOR]

Tremor, bradykinesia, and rigidity are incapacitating motor symptoms that can be suppressed with stereotactic neurosurgical treatment like deep brain stimulation (DBS) and ablative surgery (e.g., thalamotomy, pallidotomy). Traditionally, clinicians rely on clinical rating scales for intraoperative evaluation of these motor symptoms during awake stereotactic neurosurgery. However, these clinical scales have a relatively high inter-rater variability and rely on experienced raters. Therefore, objective registration (e.g., using movement sensors) is a reasonable extension for intraoperative assessment of tremor, bradykinesia, and rigidity. The main goal of this scoping review is to provide an overview of electronic motor measurements during awake stereotactic neurosurgery. The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), articles were screened for relevance. Hundred-and-three articles were subject to detailed screening. Key clinical and technical information was extracted. The inclusion criteria encompassed use of electronic motor measurements during stereotactic neurosurgery performed under local anesthesia. Twenty-three articles were included. These studies had various objectives, including correlating sensor-based outcome measures to clinical scores, identifying optimal DBS electrode positions, and translating clinical assessments to objective assessments. The studies were highly heterogeneous in device choice, sensor location, measurement protocol, design, outcome measures, and data analysis. This review shows that intraoperative quantification of motor symptoms is still limited by variable signal analysis techniques and lacking standardized measurement protocols. However, electronic motor measurements can complement visual evaluations and provide objective confirmation of correct placement of the DBS electrode and/or lesioning. On the long term, this might benefit patient outcomes and provide reliable outcome measures in scientific research. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsConclusionsClinical implicationsTo examine the effectiveness of mindfulness-based interventions (MBIs) on psychological symptoms, motor symptoms, and quality of life in patients with Parkinson’s disease (PD).Published studies in Chinese and English languages, conducted from inception to March 2023, were identified by searching PubMed, Web of Science, Cochrane Library, CINAHL, PsycINFO, and two Chinese electronic databases. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines.Twelve studies were selected for quantitative syntheses. The impact of MBIs on reducing depression and anxiety, and improving mindfulness and quality of life in PD patients was statistically significant compared to the control group. However, no statistically significant effect on motor symptoms was observed. Subgroup analysis indicated that participants from Asia, those who received face-to-face sessions, and those whose sessions lasted 1.5 hours showed a more positive effect than other subgroups.Patients with PD may benefit from MBIs to improve psychological symptoms and quality of life. MBIs represent a pivotal non-pharmacological therapeutic approach in clinical practice.MBIs confer positive improvements in psychological well-being and quality of life in PD patients. However, it remains challenging to conclusively determine their efficacy in addressing motor symptoms. [ABSTRACT FROM AUTHOR]

Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson's disease (PD). The aim of this study was to review data on gender discrepancies and gender differences in clinical outcomes in PD patients treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). Included were original studies that specifically examined gender discrepancies or gender differences in PD patients with STN-DBS. Men receive more DBS than women, for various indications. The decision-making process for DBS in women compared to men is more influenced by personal preferences and external factors. Motor symptoms improve in both genders, but bradykinesia improves more in men. The postoperative reduction of the levodopa equivalent daily dose seems to be more pronounced in men. Men show more cognitive deterioration and less improvement than women after STN-DBS. Women show more depressive symptoms before surgery, but they improve similarly to men. Men show more improvement in impulsivity and less decrease in impulsive behaviour symptoms than women. Anxiety and personality traits remain unchanged in both genders. Voice quality improves more in men and deteriorates less often than in women. Men gain fat-free mass and fat mass, but women only gain fat mass. Regarding sexual function the evidence is inconsistent. More urinary symptoms improve in women than in men. Pain and restless leg syndrome seems to improve more in men. Regarding quality of life, the evidence seems to be inconsistent, and activities of daily living seems to improve in both genders. Better prospective controlled studies, focusing directly on gender differences in PD patients treated with STN-DBS, are needed to better explain gender differences in STN-DBS for PD. [ABSTRACT FROM AUTHOR]

Background: Faced with the lack of physical activity caused by mandatory home isolation during special periods and patients' inconvenience in carrying out professionally supervised exercise, many home-based exercise programs have been developed. This systematic review and meta-analysis aimed to examine the effects of home-based exercise on measures of motor symptoms, quality of life and functional performance in Parkinson's disease (PD) patients. Methods: We performed a systematic review and meta-analysis, and searched PubMed, MEDLINE, Embase, Cochrane library, and Web of Science from their inception date to April 1, 2023. The quality of the literature was assessed using PEDro's quality scale. The data was pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). Results: A total of 20 studies involving 1885 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD = -0.29 [-0.45, -0.13]; P < 0.0001), improving quality of life (SMD = 0.20 [0.08, 0.32]; P < 0.0001), walking speed (SMD = 0.26 [0.05, 0.48]; P = 0.005), balance ability (SMD = 0.23 [0.10, 0.36]; P < 0.0001), finger dexterity (SMD = 0.28 [0.10, 0.46]; P = 0.003) and decreasing fear of falling (SMD = -0.29 [-0.49, -0.08]; P = 0.001). However, home-based exercise did not significantly relieve the overall motor symptoms of PD patients when the training period was less than 8 weeks and the total number of sessions was less than 30. Conclusion: During times of limited physical activity due to pandemics such as COVID-19, home-based exercise is an alternative to maintain and improve motor symptoms in PD patients. In addition, for the minimum dose of home-based exercise, we recommend that the exercise period is no less than 8 weeks and the total number of sessions is no less than 30 times. Trial registration: PROSPERO registration number: CRD42022329780. [ABSTRACT FROM AUTHOR]

In this research report, we present data on a "non-drug" PD subject who completed five repeated courses of (a total of 26 hours of DI) over 44 months combined with self-initiated physical exercise. The program of five repeated courses of DI has retarded the progression of some PD symptoms for 22 months or more, but then exponential growth of UPDRS-III scores did take place. The initial positive effect of the DI sessions have, at least in part, due to the placebo effect of DI. On the other hand, UPDRS-II scores remained stable, and the sense of smell persisted. Due to the DI intervention, the subject began to engage in daily physical activity, which presumably exerted noticeable "ountermeasure" effect. Overall, repeated courses of short DI sessions cannot seriously retard the progression of PD, although its initial positive effect could probably help motivating to start physical exercising counter PD disorders. [ABSTRACT FROM AUTHOR]

The mechanisms underlying motor fluctuations in patients with Parkinson's disease (PD) are currently unclear. Regional brain stimulation reported the changing of motor symptoms, but the correlation with functional connectivity (FC) in the brain network is not fully understood. Hence, our study aimed to explore the relationship between motor symptom severity and FC using resting-state functional magnetic resonance imaging (rsfMRI) in the "on" and "off" states of PD. In 26 patients with sporadic PD, FC was assessed using rsfMRI, and clinical severity was analyzed using the motor part of the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS–UPDRS Part III) in the on and off states. Correlations between FC values and MDS–UPDRS Part III scores were assessed using Pearson's correlation coefficient. The correlation between FC and motor symptoms differed in the on and off states. FC between the ipsilateral precentral gyrus (PreCG) and globus pallidus (GP) correlated with the total MDS–UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Lateralization analysis indicated that FC between the PreCG and GP correlated with the contralateral total MDS–UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Aberrant FC in cortico-striatal circuits correlated with the severity of motor symptoms in PD. Cortico-striatal hyperconnectivity, particularly in motor pathways involving PreCG and GP, is related to motor impairments in PD. These findings may facilitate our understanding of the mechanisms underlying motor symptoms in PD and aid in developing treatment strategies such as brain stimulation for motor impairment. [ABSTRACT FROM AUTHOR]

• Falls were closely related to non-motor symptoms in Parkinson's disease. • Patients with falls had higher PD-NMS, HAMD, HAMA scores. • Urinary tract symptoms, postural hypotension, depression were risk factors related to falling in patients with PD. Parkinson's disease (PD) is a chronic neurodegenerative disorder. Falls are common in patients with PD and can lead to disability, bedridden status, and death. The mechanisms of falls induced by symptoms of PD have not been fully clarified. We investigated the association between falls and nonmotor symptoms in PD patients. A total of 361 patients with Parkinson's disease were included. Whether the patients had fallen in the past half a year was recorded. Nonmotor symptoms were assessed by 30 items from the nonmotor symptom questionnaire (NMS Quest), Parkinson's Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Montreal Cognitive Assessment Scale (MOCA). A total of 63 patients experienced falls in the past six months, with an incidence of 17.5%. The patients with falls were elderly, had severe motor symptoms and disease severity, and the proportion of diabetic patients who experienced falls was higher. Adjusted for the above factors, the results showed that patients with falls had higher PD-NMS, HAMD and HAMA scores, but there was no significant difference in the total score and subscores of the MoCA scale between the two groups. The risk factors related to falling included age, history of diabetes, depression (HAMD), HAMD cognitive impairment, NMS urinary tract and NMS postural hypotension. Falls were a common symptom in patients with PD and were not only related to motor symptoms but also closely related to nonmotor symptoms. urinary tract symptoms, postural hypotension, depression and HAMD cognitive impairment were risk factors related to falling in patients with PD. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) presents with severe motor manifestations and a plethora of non-motor symptoms. Urinary dysfunctions are one of the most common non-motor symptoms of PD patients responsible for reduced quality of life. Urinary extracellular vesicles (EVs) are mostly considered to originate from the cells in the urogenital tract. In this study, we have performed urinary EV analysis in 29 PD cases with varied severity of urinary dysfunction and correlated it with the EV dynamics in 29 age-matched controls. In the studied cases, apart from urinary dysfunction, symptoms of depression, anxiety, cognitive dysfunction, sleep, and wakefulness were observed in >75% of the cases. No significant difference in urinary EV size, concentration and urinary EV protein concentration was observed between PD cases with urinary dysfunction and controls. However, a significant positive association was observed between urinary EV concentration and motor scores (p = 0.042), while no association was observed between urinary EV concentration and urinary dysfunction scores. Chronic stress induced by motor symptoms could be one of the reasons for excessive EV production in PD patients with urinary dysfunctions. Large-scale studies on the association of urinary EV dynamics with motor and non-motor symptoms may provide additional information on urinary dysfunction in PD. [ABSTRACT FROM AUTHOR]

Objective To observe the clinical characteristics of Parkinson's disease (PD) patients complicated with Pisa syndrome (PS), and to explore the influencing factors for PS occurrence in the PD patients. Methods A nested case-control study was conducted on 222 patients continuously diagnosed with PD but not with lateral spinal flexion admitted in our department from September 2020 to December 2020. After 2 years of follow-up, 26 PD patients complicated with PS were assigned into observation group, and 98 sex- and age-matched PD patients without PS complication were assigned into control group in a ratio of 1 ∶4. Their demographic and clinical data were collected, and the relevant scales and questionnaires were performed, including Hoehn and Yahr (H-Y) Staging Scale, Parkinson's Disease Questionnaire-8 (PDQ-8), Unified Parkinson's Disease Rating Scale (UPDRS), Visual Analogue Scale (VAS), Montreal Cognitive Assessment Scale (MoCA), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD). Results There were significant differences between the observation group and the control group in the course of the disease, equivalent daily dose of levodopa, drug adjustment, repeated falls within half a year, H-Y stage, UPDRS-Ⅲ score, score of axial symptoms, rigidity score, VAS score, PDQ-8 score, HAMA score, HAMD score and MoCA score (P < 0.05). Multivariate logistic regression analysis showed that the occurrence of PS was closely correlated with score of axial symptoms (OR=1.402, 95%CI=1.050~1.872, P=0.022), rigidity score (OR=1.429, 95%CI: 1.053~1.937, P=0.022) and VAS score (OR=1.772, 95%CI: 1.089~2.883, P=0.021). ROC curve analysis indicated that the AUC value of score of axial symptoms, rigidity score and VAS score was 0.899, 0.835 and 0.827, with a Youden index of 0.681, 0.558 and 0.488, respectively. Conclusion The severities of axial symptoms, rigidity and low back pain in PD patients are closely associated with the occurrence of PS.

Viorelia A Constantin,1,&ast; József A Szász,1,2,&ast; Adriana Octaviana Dulamea,3,4 Peter Valkovic,5 Jaime Kulisevsky6 1Second Clinic of Neurology, Târgu Mures County Emergency Clinical Hospital, Târgu Mureș, Romania; 2Department of Neurology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Târgu Mureș, Romania; 3Neurology Clinic, Fundeni Clinical Institute, Bucharest, Romania; 4University of Medicine and Pharmacy “Carol Davila” Bucharest, Bucharest, Romania; 5Second Department of Neurology, Comenius University Faculty of Medicine and University Hospital Bratislava, Bratislava, Slovakia; 6Movement Disorders Unit at the Neurology Department of Sant Pau Hospital, Barcelona, Spain&ast;These authors contributed equally to this workCorrespondence: Adriana Octaviana Dulamea, Tel +40212750500, Fax +40212750700, Email octaviana.dulamea@umfcd.roAbstract: A high burden of motor and non-motor parkinsonian symptoms is known to have a significant negative impact on the quality of life (QoL) of people with Parkinson’s disease (PD). Effective control of these symptoms with therapies that enable patients to maintain a good QoL is therefore a key treatment goal in PD management. When symptom control can no longer be accomplished with oral or transdermal PD treatment regimens, device-aided therapies (DAT), namely levodopa and apomorphine infusion therapies, and deep brain stimulation, are valuable options to consider. DAT options may also help reduce pill burden and thereby improve compliance with treatment. Since PD therapy relies on symptomatic management, the efficacy and tolerability of any intervention is undoubtedly important, however the impact of different therapies on patient-related outcome measures, in particular health-related QoL, is also a critical consideration for those living with a chronic and disabling condition. This review discusses clinical evidence and ongoing research regarding the QoL benefits of levodopa and apomorphine infusion therapies from studies that have used validated QoL outcome measures. The data suggest that timing of these interventions is important to achieve optimal treatment effects, and that early initiation onto infusion therapies at the point when motor fluctuations emerge, and before patient QoL and functioning have significantly declined, may provide the best long-term outcomes. Healthcare professionals caring for people with PD should therefore discuss all available DAT options with them at an early stage in the course of their disease so they can make informed and timely choices that best suit them, their families and care network.Keywords: Parkinson’s disease, infusion therapies, motor symptoms, quality of life, patient-reported outcomes

Background/Objectives: A family history of Parkinson’s disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients’ PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity.