scholarly journals Evaluating a Speech-Specific and a Computerized Step-Training-Specific Rhythmic Intervention in Parkinson's Disease: A Cross-Over, Multi-Arms Parallel Study

2022 ◽  
Vol 2 ◽  
Author(s):  
Anne Dorothée Rösch ◽  
Ethan Taub ◽  
Ute Gschwandtner ◽  
Peter Fuhr
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Repeated Measures ◽  
Statistical Analyses ◽  
Motor Deficits ◽  
Common Mechanism ◽  
Intervention Trial ◽  
Speech Rhythm ◽  
Reliable Change ◽  
Mobility Training

Background:Recent studies suggest movements of speech and gait in patients with Parkinson's Disease (PD) are impaired by a common underlying rhythmic dysfunction. If this being the case, motor deficits in speech and gait should equally benefit from rhythmic interventions regardless of whether it is a speech-specific or step-training-specific approach.Objective:In this intervention trial, we studied the effects of two rhythmic interventions on speech and gait. These rhythmic intervention programs are similar in terms of intensity and frequency (i.e., 3x per week, 45 min-long sessions for 4 weeks in total), but differ regarding therapeutic approach (rhythmic speech vs. rhythmic balance-mobility training).Methods:This study is a cross-over, parallel multi-arms, single blind intervention trial, in which PD patients treated with rhythmic speech-language therapy (rSLT; N = 16), rhythmic balance-mobility training (rBMT; N = 10), or no therapy (NT; N = 18) were compared to healthy controls (HC; N = 17; matched by age, sex, and education: p > 0.82). Velocity and cadence in speech and gait were evaluated at baseline (BL), 4 weeks (4W-T1), and 6 months (6M-T2) and correlated.Results:Parameters in speech and gait (i.e., speaking and walking velocity, as well as speech rhythm with gait cadence) were positively correlated across groups (p < 0.01). Statistical analyses involved repeated measures ANOVA across groups and time, as well as independent and one-samples t-tests for within groups analyses. Statistical analyses were amplified using Reliable Change (RC) and Reliable Change Indexes (RCI) to calculate true clinically significant changes due to the treatment on a patient individual level. Rhythmic intervention groups improved across variables and time (total Mean Difference: 3.07 [SD 1.8]; 95% CI 0.2–11.36]) compared to the NT group, whose performance declined significantly at 6 months (p < 0.01). HC outperformed rBMT and NT groups across variables and time (p < 0.001); the rSLT performed similarly to HC at 4 weeks and 6 months in speech rhythm and respiration.Conclusions:Speech and gait deficits in PD may share a common mechanism in the underlying cortical circuits. Further, rSLT was more beneficial to dysrhythmic PD patients than rBMT, likely because of the nature of the rhythmic cue.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

scholarly journals Boxing vs Sensory Exercise for Parkinson’s Disease: A Double-Blinded Randomized Controlled Trial

2021 ◽  
pp. 154596832110231
Author(s):  
Kishoree Sangarapillai ◽  
Benjamin M. Norman ◽  
Quincy J. Almeida
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Controlled Trial ◽  
Repeated Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Motor Symptoms ◽  
Post Intervention ◽  
Randomized Controlled ◽  
Double Blinded

Background. Exercise is increasingly becoming recognized as an important adjunct to medications in the clinical management of Parkinson’s disease (PD). Boxing and sensory exercise have shown immediate benefits, but whether they continue beyond program completion is unknown. This study aimed to investigate the effects of boxing and sensory training on motor symptoms of PD, and whether these benefits remain upon completion of the intervention. Methods. In this 20-week double-blinded randomized controlled trial, 40 participants with idiopathic PD were randomized into 2 treatment groups, (n = 20) boxing or (n = 20) sensory exercise. Participants completed 10 weeks of intervention. Motor symptoms were assessed at (week 0, 10, and 20) using the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Data were analyzed using SPSS, and repeated-measures ANOVA was conducted. Results. A significant interaction effect between groups and time were observed F(1, 39) = 4.566, P = .036, where the sensory group improved in comparison to the boxing group. Post hoc analysis revealed that in comparison to boxing, the effects of exercise did not wear off at washout (week 20) P < .006. Conclusion. Future rehabilitation research should incorporate similar measures to explore whether effects of exercise wear off post intervention.

scholarly journals Double dissociation of single-interval and rhythmic temporal prediction in cerebellar degeneration and Parkinson’s disease

2018 ◽  
Vol 115 (48) ◽  
pp. 12283-12288 ◽  
Author(s):  
Assaf Breska ◽  
Richard B. Ivry
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Cerebellar Degeneration ◽  
Common Mechanism ◽  
Attentional Orienting ◽  
Subcortical Structures ◽  
Double Dissociation ◽  
Temporal Prediction ◽  
Single Interval

Predicting the timing of upcoming events is critical for successful interaction in a dynamic world, and is recognized as a key computation for attentional orienting. Temporal predictions can be formed when recent events define a rhythmic structure, as well as in aperiodic streams or even in isolation, when a specified interval is known from previous exposure. However, whether predictions in these two contexts are mediated by a common mechanism, or by distinct, context-dependent mechanisms, is highly controversial. Moreover, although the basal ganglia and cerebellum have been linked to temporal processing, the role of these subcortical structures in temporal orienting of attention is unclear. To address these issues, we tested individuals with cerebellar degeneration or Parkinson’s disease, with the latter serving as a model of basal ganglia dysfunction, on temporal prediction tasks in the subsecond range. The participants performed a visual detection task in which the onset of the target was predictable, based on either a rhythmic stream of stimuli, or a single interval, specified by two events that occurred within an aperiodic stream. Patients with cerebellar degeneration showed no benefit from single-interval cuing but preserved benefit from rhythm cuing, whereas patients with Parkinson’s disease showed no benefit from rhythm cuing but preserved benefit from single-interval cuing. This double dissociation provides causal evidence for functionally nonoverlapping mechanisms of rhythm- and interval-based temporal prediction for attentional orienting, and establishes the separable contributions of the cerebellum and basal ganglia to these functions, suggesting a mechanistic specialization across timing domains.

scholarly journals The Add-On Effect of Lactobacillus plantarum PS128 in Patients With Parkinson's Disease: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chin-Song Lu ◽  
Hsiu-Chen Chang ◽  
Yi-Hsin Weng ◽  
Chiung-Chu Chen ◽  
Yi-Shan Kuo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lactobacillus Plantarum ◽  
Outcome Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Motor Deficits ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

scholarly journals Efficacy of Istradefylline, an Adenosine A2A Receptor Antagonist, as Adjunctive Therapy to Levodopa in Parkinson’s Disease: A Pooled Analysis of 8 Phase 2b/3 Trials

2021 ◽  
pp. 1-13
Author(s):  
Robert A. Hauser ◽  
Nobutaka Hattori ◽  
Hubert Fernandez ◽  
Stuart H. Isaacson ◽  
Hideki Mochizuki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Receptor Antagonist ◽  
Repeated Measures ◽  
Pooled Analysis ◽  
Adenosine A2a Receptor ◽  
A2a Receptor ◽  
Adenosine A2a Receptor Antagonist ◽  
Adenosine A2a ◽  
Off Time

Background: Istradefylline is a selective adenosine A2A receptor antagonist for the treatment of patients with Parkinson’s disease (PD) experiencing OFF episodes while on levodopa/decarboxylase inhibitor. Objective: This pooled analysis of eight randomized, placebo-controlled, double-blind phase 2b/3 studies evaluated the efficacy and safety of istradefylline. Methods: Istradefylline was evaluated in PD patients receiving levodopa with carbidopa/benserazide and experiencing motor fluctuations. Eight 12- or 16-week trials were conducted (n = 3,245); four of these studies were the basis for istradefylline’s FDA approval. Change in OFF time as assessed in patient-completed 24-h PD diaries at Week 12 was the primary endpoint. All studies were designed with common methodology, thereby permitting pooling of data. Pooled analysis results from once-daily oral istradefylline (20 and 40 mg/day) and placebo were evaluated using a mixed-model repeated-measures approach including study as a factor. Results: Among 2,719 patients (placebo, n = 992; 20 mg/day, n = 848; 40 mg/day, n = 879), OFF hours/day were reduced at Week 12 at istradefylline dosages of 20 mg/day (least-squares mean difference [LSMD] from placebo in reduction from baseline [95%CI], –0.38 h [–0.61, –0.15]) and 40 mg/day (–0.45 h [–0.68, –0.22], p <  0.0001); ON time without troublesome dyskinesia (ON-WoTD) significantly increased. Similar results were found in the four-study pool (OFF hours/day, 20 mg/day, –0.75 h [–1.10, –0.40]; 40 mg/day, –0.82 h [–1.17, –0.47]). Istradefylline was generally well-tolerated; the average study completion rate among istradefylline-treated patients across all studies was 89.2%. Dyskinesia was the most frequent adverse event (placebo, 9.6%; 20 mg/day, 16.1%; 40 mg/day, 17.7%). Conclusion: In this pooled analysis, istradefylline significantly improved OFF time and ON-WoTD relative to placebo and was well-tolerated.

scholarly journals Mitochondrial Dysfunction Induces Epigenetic Dysregulation by H3K27 Hyperacetylation to Perturb Active Enhancers in Parkinson’s Disease Models

2019 ◽  
Author(s):  
Minhong Huang ◽  
Dan Lou ◽  
Adhithiya Charli ◽  
Dehui Kong ◽  
Huajun Jin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neuronal Degeneration ◽  
Ex Vivo ◽  
Genetic Mutation ◽  
Common Mechanism ◽  
Enhancer Activity ◽  
Active Enhancer ◽  
Environmental Component

AbstractGenetic mutations explain only 10-15% of cases of Parkinson’s disease (PD), while an overriding environmental component has been implicated in the etiopathogenesis of PD. But regardless of where the underlying triggers for the onset of familial and sporadic PD fall on the gene-environment axis, mitochondrial dysfunction emerges as a common mediator of dopaminergic neuronal degeneration. Herein, we employ a multidisciplinary approach to convincingly demonstrate that neurotoxicant exposure- and genetic mutation-driven mitochondrial dysfunction share a common mechanism of epigenetic dysregulation. Under both scenarios, lysine 27 acetylation of likely variant H3.2 (H3.2K27ac) increased in dopaminergic neuronal models of PD, thereby opening that region to active enhancer activity via H3K27 hyperacetylation. These vulnerable epigenomic loci represent potential transcription factor motifs for PD pathogenesis. We further confirmed the mitochondrial dysfunction induced H3K27ac during neurodegeneration in ex vivo models of PD. Our results reveal an exciting axis of ‘exposure/mutation-mitochondrial dysfunction-metabolism-H3K27ac-transcriptome’ for PD pathogenesis. Collectively, the novel mechanistic insights presented here interlinks mitochondrial dysfunction to epigenetic transcriptional regulation in dopaminergic degeneration as well as offer potential new epigenetic intervention strategies for PD.

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