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)

Thirty patients with dementia defined by DSM-III-R criteria (Alzheimer's disease (22), vascular dementia (3), Parkinson's disease, frontal lobe dementia, possible diffuse Lewy body dementia, normal pressure hydrocephalus and uncertain diagnosis), with scores below 24 points in the Mini-Mental Status Examination and more than 4 years of education were submitted to a neuropsychological evaluation. The scores in the neuropsychological tests were compared to those obtained by thirty normal volunteers paired for age, sex and education. Sensitivity, specificity and accuracy of the tests in the distinction of demented and normal volunteers were determined. The accuracies were calculated using ROC curves. Blessed's information-memory-concentration test showed greatest accuracy, followed by copy of simple figures, delayed memory of 10 figures (after 5 minutes), recognition of 10 figures and verbal fluency test (animals). A linear discriminant function, composed by 6 tests: visual perception, incidental memory, delayed memory (after 5 minutes), drawing of a clock, verbal fluency (animals) and calculation tests, was able to discriminate all controls from patients and only one patient was wrongly classified as normal control. These tests were chosen because they can be applied in less than 10 minutes and are very easy to interpret. This discriminant function must be applied in another group of patients and controls in order to demonstrate its value. When associated to the MMSE it may be useful to discriminate patients with dementia from normal people in epidemiological studies.
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PMID:[Neuropsychological tests of simple application for diagnosing dementia]. 761 36

The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Asberg Depression Rating Scale (MADRS) against the DSM-IV diagnosis 'depressive disorder' was assessed in patients with Parkinson's disease (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the outpatient department of an academic hospital were diagnosed according to a standardised research protocol. This protocol consisted of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or absence of 'depressive disorder' according to the DSM-IV criteria, as well as the HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves) were obtained and the positive and negative predictive values (PPV, NPV) were calculated for different cut-off scores. Maximum discrimination between depressed and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD-17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and 14/15 for the MADRS, the high sensitivity and NPV make these scales good screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and 17/18 for the MADRS, the high specificity and PPV make these instruments good diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly better than that of the MADRS. This study shows that it is justified to use the HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize patient samples into depressed and non-depressed groups.
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PMID:The validity of the Hamilton and Montgomery-Asberg depression rating scales as screening and diagnostic tools for depression in Parkinson's disease. 1091 46

There is ample biochemical, pathological, and genetic evidence that the metabolism of alpha-synuclein (alpha-syn) plays a crucial role in the pathogenesis of Parkinson disease (PD). To examine whether quantification of alpha-syn in cerebrospinal fluid (CSF) is potentially informative in the diagnosis of PD, we developed a specific ELISA system and measured the concentration of alpha-syn in CSF from 33 patients with PD (diagnosed according to UK PD Society Brain Bank criteria) and 38 control subjects including 9 neurologically healthy individuals. We found that PD patients had significantly lower alpha-syn levels in their CSF than the control groups (p<0.0001) even after adjusting for gender and age. Age was independently associated with lower alpha-syn levels. Logistic regression analysis showed that reduction in CSF alpha-syn served as a significant predictor of PD beyond age and gender alone (area under ROC curve, c=0.882). Furthermore, we observed a close inverse correlation between alpha-syn levels in CSF and assigned Hoehn and Yahr score in this cohort of 71 living subjects (p<0.0001), even after adjusting for age. These findings identify in the quantification of alpha-syn from CSF a potential laboratory marker to aid the clinical diagnosis of PD.
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PMID:Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease. 1693 May 53

Leucine-rich repeat kinase 2 (LRRK2), a product of a causative gene for the autosomal-dominant form of familial Parkinson's disease (PARK8), harbors a Ras-like small GTP binding protein-like (ROC) domain besides the kinase domain, although the relationship between these two functional domains remains elusive. Here we show by thin-layer chromatographic analysis that LRRK2 stably binds GTP but lacks a GTPase activity in HEK293 and Neuro-2a cells. A ROC domain mutation that converts LRRK2 to a guanine nucleotide-free form (T1348N) abolishes the kinase activity of LRRK2 as well as its phosphate incorporation upon metabolic labeling. The phosphorylation of LRRK2 was inhibited by potential inhibitors for cyclic AMP-dependent protein kinase. These data suggest that binding of GTP to the ROC domain regulates the kinase activity of LRRK2 as well as its phosphorylation by other kinase(s).
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PMID:GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. 1726 Sep 67

Underreporting of swallowing disturbances by Parkinson's disease (PD) patients may lead to delay in diagnosis and treatment, alerting the physician to an existing dysphagia only after the first episode of aspiration pneumonia. We developed and validated a swallowing disturbance questionnaire (SDQ) for PD patients and compared its findings to an objective assessment. Fifty-seven PD patients (mean age 69 +/- 10 years) participated in this study. Each patient was queried about experiencing swallowing disturbances and asked to complete a self-reported 15-item "yes/no" questionnaire on swallowing disturbances (24 replied "no"). All study patients underwent a physical/clinical swallowing evaluation by a speech pathologist and an otolaryngologist. The 33 patients who complained of swallowing disturbances also underwent fiberoptic endoscopyic evaluation of swallowing (FEES). According to the ROC test, the "optimal" score (where the sensitivity and specificity curves cross) is 11 (sensitivity 80.5%, specificity 81.3%). Using the SDQ questionnaire substantially reduced Type I errors (specifically, an existing swallowing problem missed by the selected cutoff point). On the basis of the SDQ assessment alone, 12 of the 24 (50%) noncomplaining patients would have been referred to further evaluation that they otherwise would not have undergone. The SDQ emerged as a validated tool to detect early dysphagia in PD patients.
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PMID:Validation of a swallowing disturbance questionnaire for detecting dysphagia in patients with Parkinson's disease. 1758 37

The objective of this study was to examine the validity of the mentation, behavior, and mood items included in Part I of the Unified Parkinson's Disease Rating Scale (UPDRS) and to assess its usefulness to screen for dementia, psychosis, depression, and apathy. A consecutive series of 168 patients with PD were assessed by neurologists with the UPDRS, and by psychiatrists using a comprehensive neuropsychiatric evaluation blind to each other's ratings. ROC analysis demonstrated that a score of 2 or greater on the intellectual impairment item of the UPDRS had 60% sensitivity and 92% specificity to detect dementia, as diagnosed with DSM-IV criteria. When a score of 23 or lower on the MMSE was included as an additional classification variable, the sensitivity increased to 85%. A score of 2 or greater on the thought disorder item had 43% sensitivity and 92% specificity to detect psychotic symptoms (delusions or hallucinations). A score of 2 or greater on the depression item had 77% sensitivity and 82% specificity to detect major depression as diagnosed with DSM-IV criteria. Finally, a score of 2 or greater on the motivation/initiative item had 73% sensitivity and 65% specificity to detect apathy, as diagnosed with a standardized criteria. When the sample was divided into mild (i.e. Hohen-Yahr stages I and II) versus moderate-severe PD (i.e. Hohen-Yahr stages III-V), findings remained unchanged, except that the UPDRS show unacceptably low accuracy to detect psychosis in mild PD. The mentation, behavior, and mood section of the UPDRS is an adequate screen for depression and apathy, and has adequate sensitivity to detect dementia when combined with the Mini-Mental State Exam, but has low sensitivity to detect psychosis.
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PMID:The Unified Parkinson's Disease Rating Scale: validation study of the mentation, behavior, and mood section. 1772 77

The main objective of the present study was to test the validity of a 19-items instrument (QUICK Questionnaire, QQ) as a tool for screening of WO. Two hundred twenty-two patients (36.0% without WO; 64.0% with mild or moderate/severe WO) were included. Diagnosis of WO by the participant neurologist was considered the "gold standard." The complete Unified Parkinson's Disease Rating Scale battery, the Cumulative Illness Rating Scale-Geriatrics, and a form about WO presence and severity were completed by the neurologist. Patients independently completed the QQ just before the clinical assessment. As a whole, patients with WO were more disabled than patients without and patients with moderate/severe WO were in worse condition than patients with mild WO. The number of QQ symptoms declared to improve usually after the following dose of medication was 1.0 +/- 1.8 in the group without WO, but 6.0 +/- 3.8 in patients with WO (P < 0.001). A two QQ positive symptoms cut-off showed the following attributes: sensitivity, 88%; specificity, 80%; positive predictive value, 88.7%; negative predictive value, 79%; diagnostic accuracy, 85%; positive and negative likelihood ratios 4.4 and 0.15, respectively. The area under the ROC curve resulted 0.90 (CI95%: 0.86-0.94%). In summary, the QQ proved to be a valid screening tool to identify WO in PD patients. To our knowledge, the QQ is the only validated tool for diagnosis of WO.
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PMID:Validation of the "QUICK" questionnaire--a tool for diagnosis of "wearing-off" in patients with Parkinson's disease. 1830 46

Small guanosine triphosphatases (GTPases) have long been known to control the activities of downstream protein kinases. Some members of a rather new multidomain protein family contain not only a GTPase domain of the ROC (Ras of complex protein) subtype but also a protein kinase domain, and both domains seem to cooperate with each other in the same polypeptide. Data now show that the kinase activity of one of these ROCO proteins depends on whether guanosine diphosphate or guanosine triphosphate (GTP) is bound and that the activity is controlled by the adjacent GTPase, which suggests a novel mechanism of intrinsic control. This ROCO family member, leucine-rich repeat kinase 2 (LRRK2), is of special interest because mutations within both its protein kinase and its GTPase domains are associated with Parkinson's disease (PD). These mutations lead to abnormally enhanced protein kinase activity, which is believed to cause or at least contribute to neuronal damage. The crystal structure of the GTPase domain of LRRK2 has now been resolved and shows that the ROC GTPase domain is responsible for LRRK2 homodimerization in a surprising way. The structure not only offers insights into the molecular effects of some of the PD-associated mutations of LRRK2, but may also help to improve our understanding of the intrinsic control mechanism between a GTPase and a protein kinase within the same protein.
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PMID:ROCO kinase activity is controlled by internal GTPase function. 1854 47

The prevalence of dementia in Parkinson's disease (PD) is close to 30%, and its incidence is 4 to 6 times higher than in age-matched general population. PD with dementia (PDD) is mainly characterized by a predominant and progressive frontal-subcortical impairment. The Mattis Dementia Rating Scale (MDRS) is a commonly used screening test that sensitively measures the degree of frontal-subcortical defects. Although the MDRS has been validated as a screening test of cognitive dysfunction in nondemented PD patients (PD-ND), its utility for screening dementia in PD is unknown. In order to validate the MDRS for diagnosis of PDD it was prospectively administered to 92 PD patients (57 PD-ND, 35 PDD) fulfilling UK-PDSBB criteria. Dementia was diagnosed according to DSM-IV-TR and a Clinical Dementia Rating (CDR) scale score >or=1. Univariate, logistic regression, and ROC curve analysis were carried out to measure the discriminative power of MDRS in PDD. Regression analysis showed MDRS total scores to independently differentiate PD-ND from PDD (P < 0.001). Age and education did not predict the presence of dementia. ROC curve analysis showed a cut-off score of <or=123 on the MDRS total scores to yield high sensitivity (92.65%), specificity (91.4%), positive and negative predictive values (PPV 83.3%, NPV 96.4%). A brief version of the MDRS obtained by the addition of the memory, initiation/perseveration, and conceptualization subscores yielded similar discriminant properties. The MDRS has an excellent discriminant ability to diagnose dementia in PD and provides an objective measure to distinguish PD-ND from PDD.
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PMID:Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease. 1854 26

There are few studies about social anxiety disorder in Parkinson's disease (PD). The objective of this study was to assess its frequency and to explore the psychometric properties of the Liebowitz social anxiety scale (LSAS) in PD. Ninety patients with PD underwent neurologic and psychiatric examination. Psychiatric examination was composed by a structured clinical interview (MINI-Plus) followed by the application of the LSAS, the Hamilton depression rating scale (Ham-D), and the Hamilton anxiety rating scale (Ham-A). Neurologic examination included the MMSE, the UPDRS, the Hoehn-Yahr Scale, and the Schwab-England scale of activities of daily living. Social phobia was diagnosed in 50% of PD patients. The disorder was not associated with any sociodemographic or neurological feature, but was associated to major depression (P = 0.023), generalized anxiety disorder (P = 0.023), and obsessive-compulsive disorder (P = 0.013). The score of LSAS correlated positively with the scores of Ham-D and Ham-A (P < 0.001 for both). A ROC curve analysis of the LSAS suggested that a cutoff score in 41/42 provided the best balance between sensitivity and specificity. This disorder seems to be more common and not just restricted to performance as previously thought.
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PMID:Frequency of social phobia and psychometric properties of the Liebowitz social anxiety scale in Parkinson's disease. 1866 50


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