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Acta Bio-medica : Atenei Parmensis Oct 2017Parkinson's disease (PD) is a movement disorder, mainly affecting population consisting of the aged. PD occurs chiefly due to progressive loss of dopaminergic neurons in... (Review)
Review
Parkinson's disease (PD) is a movement disorder, mainly affecting population consisting of the aged. PD occurs chiefly due to progressive loss of dopaminergic neurons in nigrostriatal pathway. Largely, PD patients suffer from non-motor symptoms, such as depression, anxiety, fatigue, and sleep disorders, that needs further investigation and addressing during PD research. Depression in PD is a predominant and complex symptom, and its pathology exists extrinsic to the nigrostriatal system. This disease can ultimately be managed by a combination of regular physiotherapy and proper medication. Taking together the present scenario of PD, including the nature of disease, characteristics, treatment, diagnosis of the patients with PD, these outcomes were reviewed to be explored along with many speech-based solutions to PD in this study. This neurodegenerative disorder needs advancement in research and development which can help patients with PD to lead a normal life.
Topics: Humans; Parkinson Disease
PubMed: 29083328
DOI: 10.23750/abm.v88i3.6063 -
Journal of Parkinson's Disease 2020Over the past two decades, aerobic exercise has emerged as a mainstream recommendation to aid in treating Parkinson's disease (PD). Despite the acknowledgement of the... (Review)
Review
Over the past two decades, aerobic exercise has emerged as a mainstream recommendation to aid in treating Parkinson's disease (PD). Despite the acknowledgement of the benefits of exercise for people with PD (PwPD), frequently, exercise recommendations lack specificity in terms of frequency, intensity and duration. Additionally, conflating physical activity with exercise has contributed to providing vague exercise recommendations to PwPD. Therefore, the beneficial effects of exercise may not be fully realized in PwPD. Data provided by animal studies and select human trials indicate aerobic exercise may facilitate structural and functional changes in the brain. Recently, several large human clinical trials have been completed and collectively support the use of aerobic exercise, specifically high-intensity aerobic exercise, in improving PD motor symptoms. Data from these and other studies provide the basis to include aerobic exercise as an integral component in treating PD. Based on positive clinical findings and trials, it is advised that PwPD perform aerobic exercise in the following dose: 3x/week, 30-40-minute main exercise set, 60-80% of heart rate reserve or 70-85% of heart rate max. In lieu of heart rate, individuals can achieve an intensity of 14-17 on a 20-point RPE scale. Ongoing clinical trials, SPARX3 and CYCLE-II, have potential to further develop patient-specific exercise recommendations through prognostic modeling.
Topics: Animals; Exercise; Exercise Therapy; Humans; Parkinson Disease; Prescriptions
PubMed: 32925109
DOI: 10.3233/JPD-202100 -
Journal of Parkinson's Disease 2020In people with young onset Parkinson's disease (YOPD), onset of symptoms is between 21 and 40 years of age. The distinction between YOPD and late-onset Parkinson's... (Review)
Review
In people with young onset Parkinson's disease (YOPD), onset of symptoms is between 21 and 40 years of age. The distinction between YOPD and late-onset Parkinson's disease is supported by genetic differences (a genetic etiology is more common in people with YOPD) and clinical differences (e.g., dystonia and levodopa-induced dyskinesias are more common inYOPD). Moreover, people with YOPD tend to have different family and societal engagements compared to those with late-onset PD. These unique features have implications for clinical management, and call for a tailored multidisplinary approach involving shared-decision making.
Topics: Adult; Age of Onset; Disease Management; Dystonia; Female; Humans; Male; Parkinson Disease; Pregnancy; Pregnancy Complications; Social Interaction; Work Schedule Tolerance; Young Adult
PubMed: 32651336
DOI: 10.3233/JPD-202135 -
Journal of Parkinson's Disease 2020There is a need for reliable and robust Parkinson's disease biomarkers that reflect severity and are sensitive to disease modifying investigational therapeutics.
BACKGROUND
There is a need for reliable and robust Parkinson's disease biomarkers that reflect severity and are sensitive to disease modifying investigational therapeutics.
OBJECTIVE
To demonstrate the utility of EEG as a reliable, quantitative biomarker with potential as a pharmacodynamic endpoint for use in clinical assessments of neuroprotective therapeutics for Parkison's disease.
METHODS
A multi modal study was performed including aquisition of resting state EEG data and dopamine transporter PET imaging from Parkinson's disease patients off medication and compared against age-matched controls.
RESULTS
Qualitative and test/retest analysis of the EEG data demonstrated the reliability of the methods. Source localization using low resolution brain electromagnetic tomography identified significant differences in Parkinson's patients versus control subjects in the anterior cingulate and temporal lobe, areas with established association to Parkinson's disease pathology. Changes in cortico-cortical and cortico-thalamic coupling were observed as excessive EEG beta coherence in Parkinson's disease patients, and correlated with UPDRS scores and dopamine transporter activity, supporting the potential for cortical EEG coherence to serve as a reliable measure of disease severity. Using machine learning approaches, an EEG discriminant function analysis classifier was identified that parallels the loss of dopamine synapses as measured by dopamine transporter PET.
CONCLUSION
Our results support the utility of EEG in characterizing alterations in neurophysiological oscillatory activity associated with Parkinson's disease and highlight potential as a reliable method for monitoring disease progression and as a pharmacodynamic endpoint for Parkinson's disease modification therapy.
Topics: Aged; Beta Rhythm; Biomarkers; Dopamine Plasma Membrane Transport Proteins; Electroencephalography; Electroencephalography Phase Synchronization; Female; Humans; Machine Learning; Male; Middle Aged; Outcome Assessment, Health Care; Parkinson Disease; Positron-Emission Tomography
PubMed: 32116262
DOI: 10.3233/JPD-191844 -
European Review For Medical and... Jun 2015Parkinsons Disease (PD) is a neurodegenerative disorder of the dopaminergic neurons in the substantia nigra. Much of the scientific literature on the Parkinson's disease... (Review)
Review
Parkinsons Disease (PD) is a neurodegenerative disorder of the dopaminergic neurons in the substantia nigra. Much of the scientific literature on the Parkinson's disease has been focused on the evaluation and management of motor conditions in PD. Much less stress has been laid on evaluating and managing the cognitive disturbances found comorbidly in this condition. Studies have suggested that the cognitive dysfunction observed in PD can range anywhere from individual cognitive deficits to the clinical picture of minimal cognitive impairment to as much as a full-blown dementia like clinical picture. Perhaps because of this poor understanding, the treatments for this comorbidity have not been able to be adequately developed. Right now, only rivastigmine is the approved drug of choice for treatment of dementia associated with PD. In this review we aim at elaborating the individual cognitive deficits associated with PD instead of focusing on full-blown dementia. Our aim at focusing on individual symptoms is important because these symptoms should be evaluated even at the most beginning stages of PD rather than waiting for the patient to report for the symptoms. Therefore, we will aim at elaborating the prevalence, symptomatology and implications for treatment for these cognitive dysfunctions individually. Because covering all the domains of cognitive dysfunctions are not possible here, we will focus on three cognitive impairments which are most commonly observed in the PD patients. These are the (1) Executive function deficits (2) Memory deficits and (3) visuospatial deficits. We will, finally, have an overview of the condition of minimal cognitive deficits observed in PD.
Topics: Cognition; Cognition Disorders; Dementia; Humans; Neurodegenerative Diseases; Parkinson Disease
PubMed: 26166654
DOI: No ID Found -
Journal of Parkinson's Disease 2020Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only... (Review)
Review
Pain is a very frequent symptom with influence on the quality of life in Parkinson's disease (PD), but is still underdiagnosed and commonly treated only unsystematically. Pain etiology and pain character are often complex and multi-causal, and data regarding treatment recommendations are limited. Pain can be primarily related to PD but frequently it is associated with secondary diseases, such as arthrosis of the spine or joints. However, even basically PD-unrelated pain often is amplified by motor- or non-motor PD symptoms, such as akinesia or depression. Beyond an optimization of anti-parkinsonian treatment, additional pain treatment strategies are usually needed to properly address pain in PD. A careful pain history and diagnostic work-up is essential to rate the underlying pain pathophysiology and to develop a targeted therapeutic concept. This review gives an overview on how pain is treated in PD patients and how patients assess the effectiveness of these therapies; here, the manuscript focuses on pathophysiology-driven suggestions for a multimodal pain management in clinical practice.
Topics: Analgesics; Antiparkinson Agents; Humans; Pain; Pain Management; Pain Measurement; Parkinson Disease; Quality of Life
PubMed: 32568113
DOI: 10.3233/JPD-202069 -
Neuromodulation : Journal of the... Jul 2021Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the... (Review)
Review
INTRODUCTION
Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life.
MATERIALS AND METHODS
Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders.
CONCLUSION
Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.
Topics: Gait; Gait Disorders, Neurologic; Humans; Parkinson Disease; Quality of Life; Walking
PubMed: 33368872
DOI: 10.1111/ner.13347 -
Journal of Parkinson's Disease 2023Since 2020, annual reports on the clinical development of new drug-based therapies for the neurodegenerative condition of Parkinson's disease (PD) have been generated....
BACKGROUND
Since 2020, annual reports on the clinical development of new drug-based therapies for the neurodegenerative condition of Parkinson's disease (PD) have been generated. These reviews have followed the progress of both "symptomatic treatments" (ST - improves/reduces symptoms of the condition) and "disease modifying treatments" (DMT - attempts to delay/slow progression by addressing the underlying biology of PD). Additional efforts have been made to further categorize these experimental treatments based on their mechanisms of action and class of drug.
METHODS
A dataset of clinical trials for drug therapies in PD was obtained using trial data downloaded from the ClinicalTrials.gov online registry. A breakdown analysis of all the studies that were active as of January 31st, 2023, was conducted.
RESULTS
There was a total of 139 clinical trials registered on the ClinicalTrials.gov website as active (with 35 trials newly registered since our last report). Of these trials, 76 (55%) were considered ST and 63 (45%) were designated DMT. Similar to previous years, approximately a third of the studies were in Phase 1 (n = 47; 34%), half (n = 72, 52%) were in Phase 2 and there were 20 (14%) studies in Phase 3. Novel therapies again represented the most dominant group of experimental treatments in this year's report with 58 (42%) trials testing new agents. Repurposed drugs are present in a third (n = 49, 35%) of trials, with reformulations and new claims representing 19% and 4% of studies, respectively.
CONCLUSIONS
Our fourth annual review of active clinical trials evaluating ST and DMT therapeutics for PD demonstrates that the drug development pipeline is dynamic and evolving. The slow progress and lack of agents transitioning from Phase 2 to Phase 3 is concerning, but collective efforts by various stakeholders are being made to accelerate the clinical trial process, with the aim of bringing new therapies to the PD community sooner.
Topics: Humans; Parkinson Disease; Neurodegenerative Diseases
PubMed: 37302040
DOI: 10.3233/JPD-239901 -
Journal of Parkinson's Disease 2018The current mainstay treatment of Parkinson's disease (PD) consists of dopamine replacement therapy which, in addition to causing several side effects, does not delay... (Review)
Review
The current mainstay treatment of Parkinson's disease (PD) consists of dopamine replacement therapy which, in addition to causing several side effects, does not delay disease progression. The field of gene therapy offers a potential means to improve current therapy. The present review gives an update of the present status of gene therapy for PD. Both non-disease and disease modifying transgenes have been tested for PD gene therapy in animal and human studies. Non-disease modifying treatments targeting dopamine or GABA synthesis have been successful and promising at improving PD symptomatology in randomized clinical studies, but substantial testing remains before these can be implemented in the standard clinical treatment repertoire. As for disease modifying targets that theoretically offer the possibility of slowing the progression of disease, several neurotrophic factors show encouraging results in preclinical models (e.g., neurturin, GDNF, BDNF, CDNF, VEGF-A). However, so far, clinical trials have only tested neurturin, and, unfortunately, no trial has been able to meet its primary endpoint. Future clinical trials with neurotrophic factors clearly deserve to be conducted, considering the still enticing goal of actually slowing the disease process of PD. As alternative types of gene therapy, opto- and chemogenetics might also find future use in PD treatment and novel genome-editing technology could also potentially be applied as individualized gene therapy for genetic types of PD.
Topics: Animals; Disease Models, Animal; Gene Editing; Genetic Therapy; Genetic Vectors; Humans; Optogenetics; Parkinson Disease
PubMed: 29710735
DOI: 10.3233/JPD-181331 -
Journal of Parkinson's Disease 2021Human genetic studies as well as studies in animal models indicate that lysosomal dysfunction plays a key role in the pathogenesis of Parkinson's disease. Among the... (Review)
Review
Human genetic studies as well as studies in animal models indicate that lysosomal dysfunction plays a key role in the pathogenesis of Parkinson's disease. Among the lysosomal genes involved, GBA1 has the largest impact on Parkinson's disease risk. Deficiency in the GBA1 encoded enzyme glucocerebrosidase (GCase) leads to the accumulation of the GCase glycolipid substrates glucosylceramide and glucosylsphingosine and ultimately results in toxicity and inflammation and negatively affect many clinical aspects of Parkinson's disease, including disease risk, the severity of presentation, age of onset, and likelihood of progression to dementia. These findings support the view that re-establishing normal levels of GCase enzyme activity may reduce the progression of Parkinson's disease in patients carrying GBA1 mutations. Studies in mouse models indicate that PR001, a AAV9 vector-based gene therapy designed to deliver a functional GBA1 gene to the brain, suggest that this therapeutic approach may slow or stop disease progression. PR001 is currently being evaluated in clinical trials with Parkinson's disease patients carrying GBA1 mutations.
Topics: Animals; Gaucher Disease; Genetic Therapy; Glucosylceramidase; Humans; Lysosomes; Mice; Mutation; Parkinson Disease; alpha-Synuclein
PubMed: 34151863
DOI: 10.3233/JPD-212739