Journal of Parkinson's Disease - Volume 5, issue 2
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ISSN 1877-7171 (P)
ISSN 1877-718X (E)
Impact Factor 2022: 5.520
The Journal of Parkinson’s Disease is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson’s disease.
It will publish research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option.
Abstract: An increasing proportion of the individual and population risk to develop Parkinson’s disease (PD) can be explained by genetic variants of different effect strength, forming a continuum from rare high penetrance gain or loss of function mutations to relatively common genetic risk variants that only mildly modify disease risk. In the coming years, further advances in molecular genetic technologies, in particular the increasing use of next generation sequencing, is likely to generate a wealth of new knowledge about the genetic basis of PD. Although specific treatments for PD based on the underlying genetic etiology will probably not be available in…the near future, genetic testing is therefore likely to play an increasing role, both in the counselling of individual patients and their families with respect to the expected disease course and recurrence risks, and in the stratification of patient groups in clinical trials. Thus, the usefulness of genetic testing strongly depends on question asked and needs to be considered within each particular setting.
Abstract: Misfolded protein aggregates are the hallmark of several neurodegenerative diseases in humans. The main protein constituent of these aggregates and the regions within the brain that are affected differ from one neurodegenerative disorder to another. A plethora of reports suggest that distinct diseases have in common the ability of protein aggregates to spread and amplify within the central nervous system. This review summarizes briefly what is known about the nature of the protein aggregates that are infectious and the reason they are toxic to cells. The chameleon property of polypeptides which aggregation into distinct high-molecular weight assemblies is associated to…different diseases, in particular, that of alpha-synuclein which aggregation is the hallmark of distinct synucleinopathies, is discussed. Finally, strategies targeting the formation and propagation of structurally distinct alpha-synuclein assemblies associated to different synucleinopathies are presented and their therapeutic and diagnostic potential is discussed.
Keywords: Neurodegenerative diseases, Alzheimer, Parkinson, multiple system atrophy, dementia with lewy bodies, huntington, prion, protein misfolding, ageing
Abstract: Pain is a distressing non-motor symptom experienced by up to 85% of people with Parkinson’s disease (PD), yet it is often untreated. This pain is likely to be influenced by many factors, including the disease process, PD impairments as well as co-existing musculoskeletal and/or neuropathic pain conditions. Expert opinion recommends that exercise is included as one component of pain management programs; however, the effect of exercise on pain in this population is unclear. This review presents evidence describing the potential influence of exercise on the pain-related pathophysiological processes present in PD. Emerging evidence from both animal and human studies suggests…that exercise might contribute to neuroplasticity and neuro-restoration by increasing brain neurotrophic factors, synaptic strength and angiogenesis, as well as stimulating neurogenesis and improving metabolism and the immune response. These changes may be beneficial in improving the central processing of pain. There is also evidence that exercise can activate both the dopaminergic and non-dopaminergic pain inhibitory pathways, suggesting that exercise may help to modulate the experience of pain in PD. Whilst clinical data on the effects of exercise for pain relief in people with PD are scarce, and are urgently needed, preliminary guidelines are presented for exercise prescription for the management of central neuropathic, peripheral neuropathic and musculoskeletal pain in PD.
Abstract: Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the “executive-attention” network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved…in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping. In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon.
Keywords: Freezing of gait, magnetic resonance imaging, Parkinson’s disease, positron emission tomography, single photon emission computed tomography
Abstract: While the etiology and pathogenesis of Parkinson’s disease (PD) is still obscure, there is evidence for lifestyle factors influencing disease risk. Best established are the inverse associations with smoking and coffee consumption. In other contexts there is evidence that health effects of lifestyle factors may depend on gut microbiome composition. Considering the gastrointestinal involvement in PD, it was recently speculated, that the associations between smoking, coffee, and PD risk could be mediated by gut microbiota. Here we review such a possible mediatory role of gut microbiota taking into account recent findings on microbiome composition in PD and extending the scope…also to urate.
Keywords: Gut-brain axis, risk factors, non-motor symptoms, gut motility, constipation, nicotine, caffeine, inflammation, gut permeability, dietary fiber
Abstract: Background: Despite an urgent need for new medications, clinical trials in Parkinson’s have a relatively low rate of success. Although many reasons have been proposed for this, the opinions of patients and scientists, the two principal stakeholders, have not been widely canvassed. Objective: The objective of the present study was to establish the main barriers to clinical trials success in Parkinson’s, as perceived by people with Parkinson’s and those engaged in conducting clinical trials in Parkinson’s. Method: Three hundred and three people (303) with a connection to Parkinson’s completed an online four-item questionnaire, directed towards discovering…the barriers that interfere with the establishment of effective clinical trials. Results: 87% of respondents were patients and their care partners and 11% were medical professionals involved with clinical research. In the survey, those involved in conducting research cited insufficient financial and administrative support as the biggest obstacles to carrying out effective clinical trials. For responders with Parkinson’s, the principal barrier to their participation in medical research was fear of potential adverse consequences and misconceptions regarding the clinical trial system as a whole, issues rooted in a perceived lack of communication of relevant information between the research and patient communities. Conclusions: Areas for future improvement as highlighted by this survey and debated at the Rallying to the Challenge meeting of people with Parkinson’s (PwP) at the Van Andel Research Institute that followed included recommendations in the areas of communication, education, funding, recruitment and compliance.
Abstract: Background: Within Parkinson’s there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Objective: Use a data-driven approach to unravel any heterogeneity in the Parkinson’s phenotype in a well-characterised, population-based incidence cohort. Methods: 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a…confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Results: Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Conclusion: Our approach identified several Parkinson’s phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson’s.
Abstract: Background: Parkinson’s disease (PD) is a neurodegenerative disorder with fluctuating symptoms. To aid the development of a system to evaluate people with PD (PwP) at home (SENSE-PARK system) there was a need to define parameters and tools to be applied in the assessment of 6 domains: gait, bradykinesia/hypokinesia, tremor, sleep, balance and cognition. Objective: To identify relevant parameters and assessment tools of the 6 domains, from the perspective of PwP, caregivers and movement disorders specialists. Methods: A 2-round Delphi study was conducted to select a core of parameters and assessment tools to be applied. This process…included PwP, caregivers and movement disorders specialists. Results: Two hundred and thirty-three PwP, caregivers and physicians completed the first round questionnaire, and 50 the second. Results allowed the identification of parameters and assessment tools to be added to the SENSE-PARK system. The most consensual parameters were: Falls and Near Falls; Capability to Perform Activities of Daily Living; Interference with Activities of Daily Living; Capability to Process Tasks; and Capability to Recall and Retrieve Information. The most cited assessment strategies included Walkers; the Evaluation of Performance Doing Fine Motor Movements; Capability to Eat; Assessment of Sleep Quality; Identification of Circumstances and Triggers for Loose of Balance and Memory Assessment. Conclusions: An agreed set of measuring parameters, tests, tools and devices was achieved to be part of a system to evaluate PwP at home. A pattern of different perspectives was identified for each stakeholder.
Abstract: Background: Up to 89% of the individuals with Parkinson’s disease (PD) experience speech problem over the course of the disease. Speech prosody and intelligibility are two of the most affected areas in hypokinetic dysarthria. However, assessment of these areas could potentially be problematic as speech prosody and intelligibility could be affected by the type of speech materials employed. Objective: To comparatively explore the effects of different types of speech stimulus on speech prosody and intelligibility in PD speakers. Methods: Speech prosody and intelligibility of two groups of individuals with varying degree of dysarthria resulting from PD…was compared to that of a group of control speakers using sentence reading, passage reading and monologue. Acoustic analysis including measures on fundamental frequency (F0), intensity and speech rate was used to form a prosodic profile for each individual. Speech intelligibility was measured for the speakers with dysarthria using direct magnitude estimation. Results: Difference in F0 variability between the speakers with dysarthria and control speakers was only observed in sentence reading task. Difference in the average intensity level was observed for speakers with mild dysarthria to that of the control speakers. Additionally, there were stimulus effect on both intelligibility and prosodic profile. Conclusions: The prosodic profile of PD speakers was different from that of the control speakers in the more structured task, and lower intelligibility was found in less structured task. This highlighted the value of both structured and natural stimulus to evaluate speech production in PD speakers.
Abstract: Background: Urinary problems, including urinary frequency, urgency, and nocturia are some of the non-motor symptoms that correlate most with poor quality of life in Parkinson’s disease. However, the mechanism behind these symptoms is poorly understood, in particular regarding peripheral bladder pathophysiology following dopamine degeneration. Objective: In this study, we compared the contractile responsiveness of urinary bladder from the 6-OHDA unilateral rat model of Parkinson’s disease with that of normal untreated animals. Methods: The contractility of the urinary detrusor muscle was evaluated in bladder strip preparations using electrical field stimulation, and muscarinic and purinoceptor stimulations in an…vitro organ bath setup. Results: Our data show that the overall contractile response following electrical field stimulation was significantly higher (43% at maximum contraction by 20–40 Hz stimulation) in the 6-OHDA-lesioned rats as compared to control animals. This increase was associated with a significant increase in the cholinergic contractile response, where the muscarinic agonist methacholine produced a 44% (at 10 −4 M concentration) higher response in the 6-OHDA-treated rats as compared to controls with a significant left-shift of the dose response. This indicates an altered sensitivity of the muscarinic receptor system following the specific central 6-OHDA-induced dopamine depletion. In addition a 36% larger contraction of strips from the 6-OHDA animals was also observed with purinoceptor activation using the agonist ATP (5×10 −3 M) during atropine treatment. Conclusions: Our data shows that it is not only the central dopamine control of the micturition reflex that is altered in Parkinson’s disease, but also the local contractile function of the urinary bladder. The current study draws attention to a mechanism of urinary dysfunction in Parkinson’s disease that has previously not been described.