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Journal of Parkinson's Disease 2016Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin... (Review)
Review
BACKGROUND
Although vitamin D may have both protective and symptomatic effects in Parkinson's disease (PD), the evidence is scarce and not well understood. Also, 25-hydroxyvitamin D (vitamin D) is suggested to play a neuroprotective and neurotrophic role in the brain. Therefore, this review investigates the relationship between vitamin D and PD.
OBJECTIVE
Investigate the evidence for a relationship between vitamin D and PD by summarizing observational and interventional studies in humans, as well as relevant experimental studies.
METHODS
A systematic search was made in the Medline, Cochrane and Embase databases (from inception to March 2014). All identified titles were independently evaluated by two reviewers. Articles were selected based on the presence of PD-related outcome data. Included were observational studies (including genetic studies) and interventional studies in humans, as well as relevant animal studies.
RESULTS
A total of 20 studies (14 observational, 1 interventional and 5 rodent studies) were selected for analysis. Eight observational studies showed that serum 25(OH) D levels tend to be low in PD. One observational study indicated that low serum 25(OH) D may worsen automatic postural responses and one interventional study suggested that vitamin D supplementation can prevent worsening (based on the Hoehn and Yahr rating scale). Studies in rodent models of PD showed a protective effect of vitamin D treatment on dopaminergic neurons in the substantia nigra. Results of genetic studies on the association between vitamin D receptor polymorphisms and the risk of PD were contradictory.
CONCLUSION
The literature supports possible protective and symptomatic effects of vitamin D in PD. However, more observational and interventional studies in humans are needed to confirm and further elucidate the suggested beneficial effect of vitamin D on PD.
Topics: Animals; Humans; Neuroprotective Agents; Parkinson Disease; Vitamin D
PubMed: 26756741
DOI: 10.3233/JPD-150615 -
Journal of Neurology, Neurosurgery, and... Mar 2016The term SWEDD (scans without evidence for dopaminergic deficit) refers to the absence, rather than the presence, of an imaging abnormality in patients clinically... (Review)
Review
The term SWEDD (scans without evidence for dopaminergic deficit) refers to the absence, rather than the presence, of an imaging abnormality in patients clinically presumed to have Parkinson's disease (PD). However, such a term has since been widely used in the medical literature, even as a diagnostic label. While many authors have suggested that different disorders of PD lookalikes may account for a proportion of SWEDD cases, others have claimed that some of them may have a benign subtype of PD. Thus, there has been ensuing controversy and confusion and the use of this term continues without clarity of what it represents. We have systematically reviewed all the studies involving patients with SWEDD with the aim of shedding light on what these patients actually have. It becomes clear from this systematic review that while most 'SWEDD' cases are due to a clinical misdiagnosis of PD, there exists a small proportion of patients with SWEDD who may have PD on the basis of a positive levodopa response, clinical progression, imaging and/or genetic evidence. The latter challenge the seemingly incontrovertible relationship between dopaminergic tracer binding and the diagnosis of nigrostriatal parkinsonism, particularly PD. Patients with SWEDD are unlikely to reflect a single clinical entity and we suggest that the term SWEDD should be abandoned.
Topics: Diagnostic Errors; Dopaminergic Neurons; Functional Neuroimaging; Humans; Parkinson Disease; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon
PubMed: 25991401
DOI: 10.1136/jnnp-2014-310256 -
Toxicology and Applied Pharmacology Feb 2013Parkinson disease (PD) is a debilitating neurodegenerative motor disorder, with its motor symptoms largely attributable to loss of dopaminergic neurons in the substantia... (Review)
Review
Parkinson disease (PD) is a debilitating neurodegenerative motor disorder, with its motor symptoms largely attributable to loss of dopaminergic neurons in the substantia nigra. The causes of PD remain poorly understood, although environmental toxicants may play etiologic roles. Solvents are widespread neurotoxicants present in the workplace and ambient environment. Case reports of parkinsonism, including PD, have been associated with exposures to various solvents, most notably trichloroethylene (TCE). Animal toxicology studies have been conducted on various organic solvents, with some, including TCE, demonstrating potential for inducing nigral system damage. However, a confirmed animal model of solvent-induced PD has not been developed. Numerous epidemiologic studies have investigated potential links between solvents and PD, yielding mostly null or weak associations. An exception is a recent study of twins indicating possible etiologic relations with TCE and other chlorinated solvents, although findings were based on small numbers, and dose-response gradients were not observed. At present, there is no consistent evidence from either the toxicological or epidemiologic perspective that any specific solvent or class of solvents is a cause of PD. Future toxicological research that addresses mechanisms of nigral damage from TCE and its metabolites, with exposure routes and doses relevant to human exposures, is recommended. Improvements in epidemiologic research, especially with regard to quantitative characterization of long-term exposures to specific solvents, are needed to advance scientific knowledge on this topic.
Topics: Animals; Dopaminergic Neurons; Environmental Exposure; Humans; Parkinson Disease, Secondary; Solvents; Substantia Nigra; Trichloroethylene; Twin Studies as Topic
PubMed: 23220449
DOI: 10.1016/j.taap.2012.11.016 -
Neuropharmacology Jan 2013Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping. Its vigilance promoting properties and low abuse... (Review)
Review
Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping. Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer, before its neural functions were understood. Here, we review the effects of modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature. We also performed a systematic review on the effects of modafinil on neurotransmitter signalling in different areas of the brain in order to better understand the neuromechanisms of its cognitive and emotional enhancing properties. A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies. The systematic review on the neurochemical modulation of the modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively. Other neurotransmitters were also activated by modafinil in various limbic brain areas, suggesting that the drug acts on these brain regions to influence emotional responses. These reviews seek to delineate the neuronal mechanisms by which modafinil affects cognitive and emotional function. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
Topics: Affective Symptoms; Animals; Antipsychotic Agents; Benzhydryl Compounds; Brain; Brain Chemistry; Cognition; Cognition Disorders; Emotions; Humans; Modafinil; Neurons; Nootropic Agents; Schizophrenia
PubMed: 22820555
DOI: 10.1016/j.neuropharm.2012.07.011 -
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 -
Revista Espanola de Medicina Nuclear 2009(18)F-fluorodopa ((18)F-DOPA) is a functional tracer of presynaptic dopaminergic neuron terminations in the nigrostriatal system. This review is aimed to assess the... (Review)
Review
INTRODUCTION
(18)F-fluorodopa ((18)F-DOPA) is a functional tracer of presynaptic dopaminergic neuron terminations in the nigrostriatal system. This review is aimed to assess the efficacy of (18)F-DOPA-PET in the diagnosis and evaluation of the progression of Parkinson's Disease (PD) and in the differential diagnosis with other Parkinsonism Syndromes.
METHODS
A review was made of the literature by searching six databases and selecting the most relevant articles according to strict inclusion and exclusion criteria. The study data were systematically extracted and included in evidence tables.
RESULTS
Of the 1478 registries recovered through the search of the literature, 48 studies were extracted. Of these, only 13 were included in the systematic review. It was observed in all of them that PD is manifested by a lower striatal uptake of (18)F-DOPA, especially in the putamen with posterior predominance. Prospective studies have shown that there is loss of uptake with disease progression. One article described regional differences in (18)F-DOPA striatal pattern between PD, multisystem atrophy (MSA) and progressive supranuclear palsy (PSP). Cognitive impairment in PD seems to be related with (18)F-DOPA abnormal uptake in some regions of frontal cortex and caudate nucleus.
CONCLUSION
(18)F-DOPA-PET seems to be useful for the diagnosis and evaluation of PD progression. However, the evidence is not conclusive regarding its utility in the differential diagnosis with other Parkinsonism Syndromes and in the differentiation between ex novo and advanced PD.
Topics: Adult; Aged; Aged, 80 and over; Caudate Nucleus; Cognition Disorders; Corpus Striatum; Cross-Sectional Studies; Diagnosis, Differential; Dihydroxyphenylalanine; Disease Progression; Female; Fluorine Radioisotopes; Frontal Lobe; Humans; Male; Middle Aged; Movement Disorders; Parkinson Disease; Parkinsonian Disorders; Positron-Emission Tomography; Prospective Studies; Putamen; Radiopharmaceuticals; Registries
PubMed: 19558950
DOI: No ID Found -
The Cochrane Database of Systematic... Apr 2006It has been shown that central nervous system dopamine can play a major role in the pathophysiology of schizophrenia. Brain glutamate is thought to mediate symptoms in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been shown that central nervous system dopamine can play a major role in the pathophysiology of schizophrenia. Brain glutamate is thought to mediate symptoms in schizophrenia due to the influence of glutamate neurons on the dopaminergic transmission in the brain. It might be possible to decrease negative symptoms and the cognitive impairment of people with schizophrenia by treatment with glutamatergic drugs.
OBJECTIVES
To determine the efficacy of glutamatergic drugs in the treatment of schizophrenia.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's Trials Register (May 2002 and October 2003), inspected references of all identified studies and contacted relevant authors.
SELECTION CRITERIA
We included all randomised controlled trials in which glutamatergic medication was administered to people with schizophrenia.
DATA COLLECTION AND ANALYSIS
We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis.
MAIN RESULTS
We included eighteen short-term trials with 358 randomised participants. The single studies were small with numbers of participants ranging between six and 51. All trials were short-term trials with a maximum duration of 12 weeks. In all of these trials, glycine, D-serine, D-cycloserine, or ampakine CX516 was used to augment the effect of antipsychotic drugs. D-cycloserine, a partial agonist of NMDA receptors' glycine site, seemed ineffective towards the symptoms of schizophrenia. NMDA receptor co-agonists glycine and D-serine showed some effects in reducing the negative symptoms of schizophrenia (n=132, SMD -0.66, CI -1.0 to -0.3, p=0.0004), but the magnitude of the effect was moderate. Furthermore, when responder rates rather than mean scores of negative symptoms were analysed the data were inconsistent: There was no difference in responder rates between glycine and the control in terms of more than 20% improvement of negative symptoms (n=62, RR 0.70, CI 0.3 to 1.71) and only a borderline significant superiority in terms of more than 50% improvement (n=62, RR 0.87, CI 0.8 to 1.00). There were also some effects in favour of glycine and/or D-serine in terms of overall and general symptoms, but the results were again inconsistent and depended on the response definition applied. Available rating scale data on positive symptoms and cognitive functioning did not indicate a statistically significant effect of glycine or D-serine.
AUTHORS' CONCLUSIONS
In general, all glutamatergic drugs appeared to be ineffective in further reducing positive symptoms of the disease when added to the existing antipsychotic treatment. Glycine and D-serine may somewhat improve negative symptoms when added to regular antipsychotic medication, but the results were not fully consistent and data are too few to allow any firm conclusions. Many participants in the included trials were treatment-resistant which may have reduced treatment response. Additional research on glutamatergic mechanisms of schizophrenia is needed.
Topics: Antipsychotic Agents; Dopamine Antagonists; Excitatory Amino Acid Agonists; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 16625590
DOI: 10.1002/14651858.CD003730.pub2 -
BMC Medical Genetics Mar 2006Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.
METHODS
We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.
RESULTS
Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12-1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9-1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well.
CONCLUSION
We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.
Topics: Arylamine N-Acetyltransferase; Case-Control Studies; Gene Frequency; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide
PubMed: 16571112
DOI: 10.1186/1471-2350-7-30