Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkinson disease (PD) is the second most frequently occurring cerebral degenerative disease, after Alzheimer disease. Treatments are available, but their efficacy is diminished unless they are administered in the early stages. Therefore, early identification of PD is crucial. In addition to providing perfectly registered studies, simultaneous 99mTc/123I imaging makes possible the assessment of pre- and postsynaptic neurotransmission functions under identical physiological conditions, while doubling the number of counts for the same total imaging time. These advantages are limited, however, by cross talk between the two radionuclides due to the close emission energies of 99mTc (140 keV) and 123I (159 keV). PET, on the other hand, provides good temporal and spatial resolution and sensitivity but usually requires the use of a single radionuclide. In the present work, the authors compared brain PET with sequential and simultaneous dual-isotope SPECT for the task of estimating striatal activity concentration and striatal size for a normal brain and two stages of early PD. Realistic Monte Carlo simulations of a time-of-flight PET scanner and gamma cameras were performed while modeling all interactions in the brain, collimator (gamma camera) and crystal (detector block in PET), as well as population biological variability of pre- and postsynaptic uptake. For SPECT imaging, we considered two values of system energy resolution and scanners with two and three camera heads. The authors used the Cramer-Rao bound, as a surrogate for the best theoretical performance, to optimize the SPECT acquisition energy windows and objectively compare PET and SPECT. The authors determined the discrimination performance between 500 simulated subjects in every disease stage as measured by the area under the ROC curve (AUC). The discrimination accuracy between a normal subject and a subject in the prodromal disease stage was AUC = 0.924 with PET, compared to 0.863 and 0.831 with simultaneous and sequential SPECT, respectively. The significant improvement in performance obtained with simultaneous dual-isotope SPECT compared to sequential imaging (p = 0.019) was due primarily to the increased number of counts detected and resulted in comparable performance when performing simultaneous SPECT on a two-head camera with 9.2% energy resolution to that obtained with sequential SPECT on a three-head camera with 6.2% energy resolution.
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PMID:Sequential and simultaneous dual-isotope brain SPECT: comparison with PET for estimation and discrimination tasks in early Parkinson disease. 1869 58

The aim of this study was to compare the characteristics of odor discrimination and odor identification deficits in a large population of patients with Parkinson's disease (PD) and to determine which of these olfactory tests best distinguishes between patients with PD and control subjects. Olfactory performance was assessed in 404 patients with PD and 150 controls, using the odor identification and discrimination parts of the Sniffin' Sticks battery. Mean identification and discrimination scores in patients with PD were significantly lower than in controls. Linear regression analysis using a 95% confidence interval revealed that, relative to the performance of controls, 65.0% of patients with PD had an impairment in odor identification, whereas 42.1% of patients were impaired on the odor discrimination task. ROC curves revealed a higher sensitivity and specificity for odor identification than for odor discrimination in separating patients from controls. In patients with PD, odor discrimination performance decreased with increasing disease duration, whereas odor identification was not correlated with disease stage or duration. In PD, odor identification is more frequently impaired than odor discrimination and allows a better discrimination between patients and controls. Although an odor identification deficit is generally believed to be independent of disease progression, the impairment in odor discrimination appears to increase with disease duration.
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PMID:A comparative study of odor identification and odor discrimination deficits in Parkinson's disease. 1875 60

The aim of this study was to determine whether extended olfactory testing within a single olfactory task and/or across olfactory tasks increases diagnostic accuracy of olfactory testing in Parkinson's disease (PD). Olfactory function was assessed using an extended version of the "Sniffin' Sticks", comprising 32-item odor identification and discrimination tasks, and a detection threshold task in 52 PD patients and 50 controls, all aged between 49 and 78 years. ROC curves based on sensitivity and specificity estimates were used to compare the diagnostic accuracy of extended and combined olfactory testing. There was no significant difference in diagnostic accuracy between the 16-item and the 32-item versions of the odor identification or discrimination test. The single olfactory test that was best in discriminating between PD patients and controls was a 16-item odor identification test. A combination of the 16-item identification test and the detection threshold task had a significantly higher area under the curve than the 16-item odor identification test alone. In conclusion, extended testing across, and not within, olfactory tasks increases diagnostic accuracy of olfactory testing in PD. A combination of an odor detection threshold task and a 16-item odor identification test had the highest sensitivity and specificity in distinguishing between PD patients and controls.
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PMID:Extended testing across, not within, tasks raises diagnostic accuracy of smell testing in Parkinson's disease. 1885 28

The administration of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway is a rat model of Parkinson's disease (PD). The footfault test is a behavioural task in which rodents have their motor functions assessed. Here, we observed that unilaterally 6-OHDA-lesioned animals show a context-induced ipsilateral rotational behaviour when placed on the footfault apparatus for 3 min and this may be used as index to detect lesioned animals. Our results showed a sensitivity and specificity of 100% for lesions higher than 94% and 64%, respectively (ROC curve: AUC=0.988). A binary logistic regression model showed an expB=1.116 (95% CI, 1.007-1.236) and C=-9.081+/-4.554 (p=0.046) using the nigral tyrosine hidroxylase immunocontent as standard (each unit represents a 10%-lesion extension). Additionally, the footfault test was more sensitive than apomorphine challenging at 1mg/kg when these tests were carried out days apart and it was less sensitive than methylphenidate at 40 mg/kg (sign test, p<0.05). Therefore, the footfault test may be very useful in the PD animal model for screening animals since it is fast and simple and it does not require a drug to induce rotational activity.
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PMID:The footfault test as a screening tool in the 6-hydroxydopamine rat model of Parkinson's disease. 1902 86

Patients with Leucine-rich repeat kinase 2 (LRRK2) linked Parkinson's disease (PD) clinically present with typical idiopathic PD. However, LRRK2-linked PD displays a pleomorphic neuropathology and high variability in age at disease onset (AAO) which suggests that environmental and/or genetic factors other than the mutation itself influence the course of the disease. We investigated the modulation of AAO by genetic factors including the mutation-containing domain and PD associated polymorphisms in the gene coding alpha-synuclein (SNCA) and tau (MAPT) in 44 patients from 19 affected families. Using this limited number of available LRRK2 mutation carriers, we provide evidence that mutations in the kinase domain of Lrrk2 significantly decrease AAO compared to mutations in the ROC (Ras/GTPase of complex proteins) domain. Furthermore, polymorphic variations in MAPT show a significant association with AAO in individuals with LRRK2 mutations. Our results await replication in future studies with a larger number of LRRK2 mutation carriers, but indicate an association of mutation-affected protein domain and mutation-extrinsic genetic factors with AAO and suggest that these factors could contribute to explain the phenotypic heterogeneity observed in LRRK2-linked PD.
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PMID:Genetic factors influencing age at onset in LRRK2-linked Parkinson disease. 1904 Dec 74

As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management.
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PMID:Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease. 1945 62

LRRK2 is a 250 kDa multidomain protein, mutations in which cause familial Parkinson's disease. Previously, we have demonstrated that the R1441C mutation in the ROC domain decreases GTPase activity. Here we show that the R1441C alters the folding properties of the ROC domain, lowering its thermodynamic stability. Similar to small GTPases, binding of different guanosine nucleotides alters the stability of the ROC domain, suggesting that there is an alteration in conformation dependent on GDP or GTP occupying the active site. GTP/GDP bound state also alters the self-interaction of the ROC domain, accentuating the impact of the R1441C mutation on this property. These data suggest a mechanism whereby the R1441C mutation can reduce the GTPase activity of LRRK2, and highlights the possibility of targeting the stability of the ROC domain as a therapeutic avenue in LRRK2 disease.
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PMID:The R1441C mutation alters the folding properties of the ROC domain of LRRK2. 1978 41

Parkinson's disease (PD) is a major adult-onset neurodegenerative disorder affecting the extrapyramidal motor system. A subset of patients develop PD as an autosomal dominant trait, of which PARK8 caused by mutations in the leucine-rich repeat kinase 2 (LRRK2) gene is highlighted because of its high frequency and clinicopathological similarity to sporadic PD. Previous studies have suggested that overactivation of LRRK2 caused by missense mutations leads to neuronal toxicity in PARK8, although the regulatory mechanism that governs the kinase activity of LRRK2 remains unknown. In this study, we expressed the carboxyl-half fragments of LRRK2 (DeltaN-LRRK2) that harbors the kinase as well as the ras-like (ROC) domains in Sf9 cells, subjected them to in vitro phosphorylation reaction, and analyzed the autophosphorylation by matrix assisted laser desorption/ionization- time of flight (MALDI-TOF) mass spectrometer. We identified Ser1403, Thr1404, Thr1410, Thr1491 located within the ROC domain, as well as Thr1967 and Thr1969 in the kinase domain, as the autophosphorylation sites. Substitution of Thr1967, an autophosphorylation site located within the kinase domain, to Ala caused a significant decrease in the kinase activity, implicating Thr1967 in the kinase activity of LRRK2. Phosphospecific antibodies to the autophosphorylation sites specifically recognized full-length LRRK2 subjected to in vitro phosphorylation reaction, indicating that the autophosphorylation takes place in holoproteins. Further analysis of autophosphorylation will clarify the mechanism of activation of LRRK2, as well as the pathomechanism of PD in relation to overactivation of LRRK2.
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PMID:Identification of the autophosphorylation sites of LRRK2. 1982 98

Mutations in the LRRK2 gene have been implicated in the pathogenesis of Parkinson's disease. This work provides biochemical evidence that the ROC domain of LRRK2 functions as a small GTPase, and the Parkinson's disease-associated mutants do not appear to have reduced GTP hydrolysis activities.
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PMID:The small GTPase activity of the ROC domain from LRRK2, a Parkinson's disease related protein. 2000 6

Psychogenic movement disorders (PMD) represent a diagnostically challenging group of patients in movement disorders. Finger tapping tests (FTT) have been used in neuropsychiatric evaluations to identify psychogenic conditions, but their use in movement disorders has been limited to the quantification of upper extremity disability in idiopathic Parkinson disease (IPD). We evaluated the ability of the FTT to objectively identify PMD by screening 195 individuals from a movement disorder clinic with IPD, dystonia, essential tremor, or PMD and compared them to 130 normal adults. All subjects performed six-30 s trials using alternate hands. We compared mean FTT score and the coefficient of variation between diagnostic groups. FTT scores in IPD were inversely correlated with Hoehn and Yahr stage (p < 0.001) and the United Parkinson Disease Rating Scale III (motor) subscale (p < 0.001). FTT scores were significantly lower in PMD (mean = 41.72) when compared to the other diagnostic groups after controlling for age. The coefficient of variation was not significantly different between diagnostic groups. ROC analysis identified a cutoff FTT ratio of 0.670 or less was 89.1% specific and 76.9% sensitive for the diagnosis of PMD. We conclude the FTT can provide supportive evidence for the diagnosis of PMD.
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PMID:Sensitivity and specificity of the finger tapping task for the detection of psychogenic movement disorders. 2000 66


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