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Journal of Parkinson's Disease 2019Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is... (Review)
Review
Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.
Topics: Female; Humans; Inflammation; Male; Oxidative Stress; Parkinson Disease; Sex Characteristics
PubMed: 31282427
DOI: 10.3233/JPD-191683 -
Journal of Parkinson's Disease 2022Fueled by aging populations and continued environmental contamination, the global burden of Parkinson's disease (PD) is increasing. The disease, or more appropriately... (Review)
Review
Fueled by aging populations and continued environmental contamination, the global burden of Parkinson's disease (PD) is increasing. The disease, or more appropriately diseases, have multiple environmental and genetic influences but no approved disease modifying therapy. Additionally, efforts to prevent this debilitating disease have been limited. As numerous environmental contaminants (e.g., pesticides, metals, industrial chemicals) are implicated in PD, disease prevention is possible. To reduce the burden of PD, we have compiled preclinical and clinical research priorities that highlight both disease prediction and primary prevention. Though not exhaustive, the "PD prevention agenda" builds upon many years of research by our colleagues and proposes next steps through the lens of modifiable risk factors. The agenda identifies ten specific areas of further inquiry and considers the funding and policy changes that will be necessary to help prevent the world's fastest growing brain disease.
Topics: Humans; Parkinson Disease; Pesticides
PubMed: 34719434
DOI: 10.3233/JPD-212922 -
Sensors (Basel, Switzerland) Feb 2020Rigidity is one of the cardinal symptoms of Parkinson´s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these...
Rigidity is one of the cardinal symptoms of Parkinson´s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these instruments show limitations due to their subjectivity and poor intra- and inter-rater reliability. To compile all of the objective quantitative methods used to assess rigidity in PD and to study their validity and reliability, a systematic review was conducted using the Web of Science, PubMed, and Scopus databases. Studies from January 1975 to June 2019 were included, all of which were written in English. The Strengthening the Reporting of observational studies in Epidemiology Statement (STROBE) checklist for observational studies was used to assess the methodological rigor of the included studies. Thirty-six studies were included. Rigidity was quantitatively assessed in three ways, using servomotors, inertial sensors, and biomechanical and neurophysiological study of muscles. All methods showed good validity and reliability, good correlation with clinical scales, and were useful for detecting rigidity and studying its evolution. People with PD exhibit higher values in terms of objective muscle stiffness than healthy controls. Rigidity depends on the angular velocity and articular amplitude of the mobilization applied. There are objective, valid, and reliable methods that can be used to quantitatively assess rigidity in people with PD.
Topics: Electromyography; Humans; Joints; Movement; Muscle Rigidity; Muscles; Observational Studies as Topic; Parkinson Disease
PubMed: 32041374
DOI: 10.3390/s20030880 -
Ageing Research Reviews Feb 2022Cognitive symptoms of Parkinson's disease (PD) have been long underestimated, but are some of the most disabling non-motor features of the disease. In order to establish... (Review)
Review
Cognitive symptoms of Parkinson's disease (PD) have been long underestimated, but are some of the most disabling non-motor features of the disease. In order to establish signs that allow for earlier detection of cognitive decline in PD, the concept of `subjective cognitive decline´ (SCD) has gained a growing interest. SCD refers to patients who report a decline in subjective cognitive capacities, while their results on neuropsychological tests are within the normal performance range, indicating adequate cognitive functions. The aim of this review was to evaluate the concept of SCD in PD and give an overview of the current research. A systematic literature search in PubMed was performed to identify articles published before December 2020. We included 18 studies with a total of n = 2,654 patients. While there is currently no consensus on research or clinical criteria for SCD in PD, this review presents the accumulated evidence for SCD in PD patients and supports the importance of early identification of cognitive deficits, due to the relatively high prevalence for SCD in PD and the added risk of future cognitive impairment it entails. The publications included in this review indicate that SCD may be part of the PD spectrum but further research is needed. Expanding research on SCD in PD will allow for earlier detection of cognitive impairment and may foster preventive interventions.
Topics: Cognition; Cognitive Dysfunction; Humans; Neuropsychological Tests; Parkinson Disease
PubMed: 34740867
DOI: 10.1016/j.arr.2021.101508 -
Cellular and Molecular Life Sciences :... Dec 2020Glial cells have been identified more than 100 years ago, and are known to play a key role in the central nervous system (CNS) function. A recent piece of evidence is... (Review)
Review
Glial cells have been identified more than 100 years ago, and are known to play a key role in the central nervous system (CNS) function. A recent piece of evidence is emerging showing that in addition to the capacity of CNS modulation and homeostasis, glial cells are also being looked like as a promising cell source not only to study CNS pathologies initiation and progression but also to the establishment and development of new therapeutic strategies. Thus, in the present review, we will discuss the current evidence regarding glial cells' contribution to neurodegenerative diseases as Parkinson's disease, providing cellular, molecular, functional, and behavioral data supporting its active role in disease initiation, progression, and treatment. As so, considering their functional relevance, glial cells may be important to the understanding of the underlying mechanisms regarding neuronal-glial networks in neurodegeneration/regeneration processes, which may open new research opportunities for their future use as a target or treatment in human clinical trials.
Topics: Cell- and Tissue-Based Therapy; Central Nervous System; Humans; Nerve Degeneration; Neuroglia; Neurons; Parkinson Disease
PubMed: 32617639
DOI: 10.1007/s00018-020-03584-x -
Journal of Parkinson's Disease 2021Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from... (Review)
Review
Mitochondrial dysfunction represents a well-established player in the pathogenesis of both monogenic and idiopathic Parkinson's disease (PD). Initially originating from the observation that mitochondrial toxins cause PD, findings from genetic PD supported a contribution of mitochondrial dysfunction to the disease. Here, proteins encoded by the autosomal recessively inherited PD genes Parkin, PTEN-induced kinase 1 (PINK1), and DJ-1 are involved in mitochondrial pathways. Additional evidence for mitochondrial dysfunction stems from models of autosomal-dominant PD due to mutations in alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2). Moreover, patients harboring alterations in mitochondrial polymerase gamma (POLG) often exhibit signs of parkinsonism. While some molecular studies suggest that mitochondrial dysfunction is a primary event in PD, others speculate that it is the result of impaired mitochondrial clearance. Most recent research even implicated damage-associated molecular patterns released from non-degraded mitochondria in neuroinflammatory processes in PD. Here, we summarize the manifold literature dealing with mitochondria in the context of PD. Moreover, in light of recent advances in the field of personalized medicine, patient stratification according to the degree of mitochondrial impairment followed by mitochondrial enhancement therapy may hold potential for at least a subset of genetic and idiopathic PD cases. Thus, in the second part of this review, we discuss therapeutic approaches targeting mitochondrial dysfunction with the aim to prevent or delay neurodegeneration in PD.
Topics: Animals; Humans; Mitochondrial Diseases; Parkinson Disease
PubMed: 33074190
DOI: 10.3233/JPD-201981 -
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 -
Scandinavian Journal of Immunology May 2021For many years, it was postulated that the brain is the organ behind the barrier with an autonomous need for its maintenance. This view has been changed by the concept... (Review)
Review
For many years, it was postulated that the brain is the organ behind the barrier with an autonomous need for its maintenance. This view has been changed by the concept that the central nervous system is sensitive to the immune processes occurring in the periphery as well as to the infiltration of peripheral immune cells. However, how the immune system might contribute to the development of neurodegenerative diseases, such as Parkinson's disease (PD), remains unclear. PD is a chronic neurodegenerative disorder that affects motor and cognitive functions. Although the precise cause of PD is unknown, studies in both mice and human suggest that alterations in the innate immunity may play a critical role in modulating PD progression. Here, we review recent advancements in our understanding of inflammation and the innate immune mechanisms in PD pathology.
Topics: Animals; Central Nervous System; Humans; Immunity, Innate; Inflammation; Mice; Microglia; Neuroimmunomodulation; Parkinson Disease; alpha-Synuclein
PubMed: 33471378
DOI: 10.1111/sji.13022 -
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 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