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Neurophysiologie Clinique = Clinical... Apr 2019Parkinson's disease (PD) is known to have a long prodromal stage due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta over the course of...
Parkinson's disease (PD) is known to have a long prodromal stage due to the degeneration of dopaminergic neurons of the substantia nigra pars compacta over the course of many years without clinical manifestations of PD. When the diagnosis is made, the neuropathological process is already well entrenched. Consequently, identifying individuals during this prodromal period could be very helpful for future trials of neuroprotective or disease-modifying therapies, which might slow or prevent the degeneration of dopaminergic neurons. Thus, efforts are needed to determine appropriate early markers of PD. Gait and balance disorders are frequent during the early stages of PD. This systematic review aims to determine if gait and balance disorders occur before the diagnosis of PD and if so, whether they could be used as markers of preclinical PD. Findings reveal that, at the presymptomatic stage of PD, impaired basal ganglia function leads to disorders in gait and balance. Both clinical and instrumental assessments allow early detection of these disorders, particularly when performed under challenging conditions (e.g. dual-task). Among all studied parameters, temporal gait variability and arm kinematics appear to be promising markers of preclinical PD.
Topics: Biomarkers; Early Diagnosis; Gait Disorders, Neurologic; Humans; Locomotion; Parkinson Disease; Postural Balance
PubMed: 30686671
DOI: 10.1016/j.neucli.2019.01.001 -
Cureus Aug 2021Parkinson's disease (PD) is a neurodegenerative disease caused due to the destruction of dopaminergic neurons and the deposition of α-synuclein proteins, known as Lewy... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease caused due to the destruction of dopaminergic neurons and the deposition of α-synuclein proteins, known as Lewy bodies. Generally, the diagnosis of PD is centered around motor symptoms. However, the early recognition of non-motor symptoms such as autonomic dysfunction, sleep disturbances, and cognitive and psychiatric disturbances are gaining increased attention for the early diagnosis of PD. Rapid eye movement (REM) sleep behavior disorder or REM sleep behavior disorder (RBD) is described as parasomnia, which is a condition of loss of normal muscle atonia causing the person to act out vivid dreams and it has been seen to be associated with the misprocessing of intercellular α-synuclein leading to neurodegenerative diseases such as PD. This review's objective is to highlight the significance of RBD as a prodromal premotor marker for the early detection of PD. We used PubMed as our primary database to search for articles on May 2, 2021, and a total of 1849 articles were found in our initial search using keywords and medical subject heading (MeSH) keywords. Thereafter, we removed the duplicates, applied the inclusion/exclusion criteria, and did a quality appraisal to include 10 articles in this study. We concluded that the recognition and diagnosis of RBD are of paramount importance to detect early PD, and further longitudinal studies and clinical trials are of utmost importance to understand their correlation; also, treatment trials are needed to prevent the phenoconversion of RBD into PD.
PubMed: 34522507
DOI: 10.7759/cureus.17026 -
Neurodegenerative Disease Management Jun 2022Parkinson's disease (PD) is a progressive neurological disorder that predominately affects dopaminergic neurons. We believe that this pooling of data will help to... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is a progressive neurological disorder that predominately affects dopaminergic neurons. We believe that this pooling of data will help to better understand the prodromal nature of depression in PD. We conducted this study in accordance with PRISMA guidelines 2020. Fifteen eligible articles were shortlisted for final analysis. Risk of bias assessment was also conducted The random-effect model revealed that the risk of subsequent PD in patients with prodromal depression was twice as likely (odds ratio, 2.04; 95% CI, 1.02-4.08) as compared with a healthy population. Our meta-analysis concluded that the subsequent risk of PD is significantly higher in patients with depression as compared with healthy individuals.
Topics: Depression; Humans; Parkinson Disease; Prodromal Symptoms
PubMed: 35512296
DOI: 10.2217/nmt-2022-0001 -
Journal of Parkinson's Disease 2021The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease progression. However, intraneuronal levels of dopamine have not been reported.
OBJECTIVE
Meta-analytic methods were utilized to determine intracellular dopamine levels in Parkinson's disease.
METHODS
A systematic review of the literature and frequentist meta-analyses were performed. Dopamine levels were scaled for cell and axon numbers as well as VMAT2 protein levels.
RESULTS
Reduced tissue dopamine, dopaminergic cell bodies and VMAT2 protein were confirmed. The ratio of Parkinson's to normal brain intracellular dopamine scaled for either cell or axon number, each with VMAT2 level in the caudate ranged from 1.49 to 1.87 (p = 0.51 and p = 0.12, respectively) and in the putamen from 0.75 to 4.61 (p = 0.40 and 0.001, respectively).
CONCLUSION
Free, intracellular dopamine levels are not reduced in Parkinson's disease compared to normals to a similar degree as are total tissue concentrations, supporting the relevance of modulating VMAT2, neuromelanin and/or dopamine synthesis as rational neuroprotective strategies.
Topics: Basal Ganglia; Dopamine; Dopaminergic Neurons; Humans; Parkinson Disease; Putamen
PubMed: 34024786
DOI: 10.3233/JPD-212715 -
Brain Sciences Nov 2021Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson's disease (PD), hence the unmet need for the provision of... (Review)
Review
Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson's disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed, and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.
PubMed: 34942876
DOI: 10.3390/brainsci11121573 -
Explaining ADAGIO: a critical review of the biological basis for the clinical effects of rasagiline.Movement Disorders : Official Journal... Nov 2011The ADAGIO study demonstrated a symptomatic benefit for rasagiline in early Parkinson's disease (PD) and suggested a disease-modifying effect. Evidence indicates that... (Review)
Review
The ADAGIO study demonstrated a symptomatic benefit for rasagiline in early Parkinson's disease (PD) and suggested a disease-modifying effect. Evidence indicates that mitochondrial dysfunction plays a role in the pathogenesis of PD and that this may be the site of effect for rasagiline. In this systematic review, evidence for the role of mitochondria in the pathogenesis of PD are reviewed in light of other proposed mechanisms of neuronal degeneration and the actions of rasagiline and its component parts, namely propargylamine and the metabolite, aminoindan. Evidence for the role of mitochondria in the pathogenesis and treatment of PD are reviewed in light of other proposed mechanisms of neuronal degeneration and clinical actions of rasagiline. Monoamine oxidase B (MAO-B) located in the outer mitochondrial membrane controls dopamine metabolism in early PD, and this is the likely location for the symptomatic action of rasagiline. Accumulating evidence indicates that mitochondrial impairment contributes to dopaminergic neuronal loss in PD, either directly or through other mechanisms such as oxidative stress or protein misfolding. Further rasagiline affects numerous mitochondrial mechanisms that prevent apoptotic cell death including prevention of opening of the mitochondrial transition pore, decreased release of cytochrome C, alterations in pro-antiapoptotic genes and proteins, and the nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Thus, the functional neuroprotective actions of rasagiline may not be dependent on MAO-B inhibition, but rather may involve actions of the propargylamine moiety and the aminoindan metabolite. An accumulating body of literature indicates a mitochondrial site of action for rasagiline and highlights the neuroprotective action of the drug, providing strong biological plausibility for disease-modifying effects of the drug such as those observed in ADAGIO.
Topics: Animals; Cell Death; Clinical Trials as Topic; Humans; Indans; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurons; Neuroprotective Agents; Parkinson Disease
PubMed: 21953831
DOI: 10.1002/mds.23926 -
Clinical Parkinsonism & Related... 2021Smooth pursuit eye movement (SPEM) abnormalities are commonly seen in Parkinson's disease (PD). Both reduced speed and saccades seen during SPEM, also known as saccadic... (Review)
Review
Smooth pursuit eye movement (SPEM) abnormalities are commonly seen in Parkinson's disease (PD). Both reduced speed and saccades seen during SPEM, also known as saccadic pursuit (SP), have been studied in PD. A comprehensive literature review analyzed 26 studies of SPEM and PD. It appears that a greater proportion of PD patients have SPEM abnormalities consisting of reduced SPEM gain and/or SP compared to the normal population. It is not clear whether SPEM abnormalities are present early in the disease or begin sometime during disease progression. SPEM abnormalities may be correlated with disease severity but do not fluctuate or respond to dopaminergic medication in the same manner as other motor symptoms in PD. SPEM in PD is composed of normal SPEM interspersed with SP composed of both catch up and anticipatory saccades. This differs from other neurodegenerative disorders and may be related to an inability to inhibit extraneous saccades or to increased distraction reflecting executive dysfunction. Because the basal ganglia are involved in SPEM physiology, degeneration of the SNr neurons in PD may explain abnormal SPEM in this disorder. Since dementia, aging and medication effects influence SPEM, they should be controlled for in future studies of SPEM in PD. SP is easily detected on clinical exam and may be a biomarker for the disease or for disease progression. Oculomotor testing can be an important part of the Parkinson's exam.
PubMed: 34316663
DOI: 10.1016/j.prdoa.2020.100085 -
Pediatric Research Jun 2020Antenatal corticosteroids (ACSs) are recommended to all women at risk for preterm delivery; currently, there is controversy about the subsequent long-term neurocognitive...
BACKGROUND
Antenatal corticosteroids (ACSs) are recommended to all women at risk for preterm delivery; currently, there is controversy about the subsequent long-term neurocognitive sequelae. This systematic review summarizes the long-term neurodevelopmental outcomes after ACS therapy in animal models.
METHODS
An electronic search strategy incorporating MeSH and keywords was performed using all known literature databases and in accordance with PRISMA guidance (PROSPERO CRD42019119663).
RESULTS
Of the 669 studies identified, eventually 64 were included. The majority of studies utilized dexamethasone at relative high dosages and primarily involved rodents. There was a high risk of bias, mostly due to lack of randomization, allocation concealment, and blinding. The main outcomes reported on was neuropathological, particularly glucocorticoid receptor expression and neuron densities, and neurobehavior. Overall there was an upregulation of glucocorticoid receptors with lower neuron densities and a dysregulation of the dopaminergic and serotonergic systems. This coincided with various adverse neurobehavioral outcomes.
CONCLUSIONS
In animal models, ACSs consistently lead to deleterious long-term neurocognitive effects. This may be due to the specific agents, i.e., dexamethasone, or the repetitive/higher total dosing used. ACS administration varied significantly between studies and there was a high risk of bias. Future research should be standardized in well-characterized models.
Topics: Animals; Behavior, Animal; Central Nervous System; Dexamethasone; Female; Glucocorticoids; Humans; Models, Animal; Pregnancy; Premature Birth; Prenatal Exposure Delayed Effects
PubMed: 31822018
DOI: 10.1038/s41390-019-0712-1 -
Alcohol and Alcoholism (Oxford,... Feb 2021The appetite regulating hormone leptin, which is mainly secreted from adipose tissue, is an important regulator of food intake and modulator of reward-driven behavior....
AIMS
The appetite regulating hormone leptin, which is mainly secreted from adipose tissue, is an important regulator of food intake and modulator of reward-driven behavior. Leptin exerts its biological actions via binding to the leptin receptor, which is expressed in the hypothalamus, but also in the hippocampus, the amygdala and the substantia nigra. In the ventral tegmental area (VTA), leptin attenuates the firing rate of dopaminergic neurons that project to the Nucleus accumbens (NAc), which serves as relay to other brain areas of the "addiction network", such as the prefrontal cortex. This suggests that leptin plays a role in the processing of rewards in the context of substance use disorders such as alcohol use disorder, especially through attenuation of dopaminergic activity in the mesolimbic reward system. This supports the plausibility of leptin's potential effects in alcohol use disorder.
METHODS
We searched MEDLINE from 1990 to February 2020. All abstracts were screened for relevance and we only included publications reporting original data with a full text available in English language. Studies that did not report leptin-data, reviews or case reports/series were not included.
RESULTS
We identified a total of N=293 studies of whom a total of N=55 preclinical and clinical studies met the specified criteria. N=40 studies investigated the effects of alcohol on leptin plasma levels, N=9 studies investigated the effects of leptin on alcohol craving and N=6 studies investigated the effects of leptin on relapse and alcohol consumption.
CONCLUSIONS
In this review of preclinical and clinical data, we assess the role of leptin in alcohol use and the development and maintenance of an alcohol use disorder, alcohol craving and relapse. Integrating the existing preclinical and clinical data on leptin may reveal new and innovative targets for the treatment of substance use disorders in the future.
Topics: Alcohol Drinking; Animals; Behavior, Addictive; Craving; Dopaminergic Neurons; Female; Humans; Leptin; Male; Mice; Nucleus Accumbens; Rats; Ventral Tegmental Area
PubMed: 32490525
DOI: 10.1093/alcalc/agaa044 -
Frontiers in Pharmacology 2021Parkinson's disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor... (Review)
Review
Parkinson's disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor function impairment. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-PD efficacy in PD models. Among those compounds, resveratrol, a polyphenol found in many common plants and fruits, is more effective against PD. Resveratrol has displayed a potent neuroprotective efficacy in several PD animal models. However, there is still no systematic analysis of the quality of methodological design of these studies, nor of their results. In this review, we retrieved and analyzed 18 studies describing the therapeutic effect of resveratrol on PD animal models. There are 5 main kinds of PD rodent models involved in the 18 articles, including chemical-induced (MPTP, rotenone, 6-OHDA, paraquat, and maneb) and transgenic PD models. The neuroprotective mechanisms of resveratrol were mainly concentrated on the antioxidation, anti-inflammation, ameliorating mitochondrial dysfunction, and motor function. We discussed the disadvantages of different PD animal models, and we used meta-analysis approach to evaluate the results of the selected studies and used SYRCLE's risk of bias tool to evaluate the methodological quality. Our analytical approach minimized the bias of different studies. We have also summarized the pharmacological mechanisms of resveratrol on PD models as reported by the researchers. The results of this study support the notion that resveratrol has significant neuroprotective effects on different PD models quantified using qualitative and quantitative methods. The collective information in our review can guide researchers to further plan their future experiments without any hassle regarding preclinical and clinical studies. In addition, this collective assessment of animal studies can provide a qualitative analysis of different PD animal models, either to guide further testing of these models or to avoid unnecessary duplication in their future research.
PubMed: 33967780
DOI: 10.3389/fphar.2021.644219