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)

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) improves Parkinson's disease and increases frontal blood flow. We assessed the effects of bilateral DBS on executive function in Parkinson's disease patients, seven with electrodes implanted in the STN and six in the GPi. Patients were assessed off medication with stimulators off, on and off again. The groups showed differential change with stimulation on the Reitan Trail-Making test (TMT B) (STN more improved) and on some measures of random number generation and Wisconsin Card Sorting (STN improved, GPi worse with stimulation). Across the groups, stimulation speeded up responding (Stroop control trial, TMT A) and improved performance on paced serial addition and missing digit tests. Conversely, conditional associative learning became more errorful with stimulation across the two groups. In general, change in performance with stimulation was significant for the STN but not the GPi group. These results support two opposite predictions. In support of current models of Parkinson's disease, 'releasing the brake' on frontal function with DBS improved aspects of executive function. Conversely, disruption of basal ganglia outflow during DBS impaired performance on tests requiring changing behaviour in novel contexts as predicted by Marsden and Obeso in 1994.
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PMID:The impact of deep brain stimulation on executive function in Parkinson's disease. 1082 53

The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been under investigation by numerous researchers around the world for the last two decades. The association of a number of defects in both phase I and phase II reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been extensively studied. This review of the work of the group based initially at the University of Birmingham into the functional genomics of XMEs and neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD and MND can be identified with problems in xenobiotic metabolism by in vivo or in vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S-oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic oxidase(s). The odds risk ratio for the association of this defect with these diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD appear to have an altered substrate specificity for monoamine oxidase B substrates in an in vitro platelet assay. 4. Patients with MND have an increased capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as well as an in vitro erythrocyte thiol methyltransferase assay. The results of over a decade of investigations into both PD and MND indicate that these are diseases with mutifactorial origins that encompass both genetic predisposition and environmental insult.
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PMID:A review of xenobiotic metabolism enzymes in Parkinson's disease and motor neuron disease. 1146 Aug 78

Executive function declines in Parkinson's disease (PD). However, it has not been clearly shown at what stage in PD, this decline starts to occur. We here report a study aiming to answer this question. We conducted Wisconsin Card Sorting Test (WCST) and Trail Making Test A and B (TMT A, B) in three normal control groups (young, adult, and aged) and three PD patients groups (Hoehn & Yahr stage I, II, and III). We intend to analyze at what age or stage the decline in executive function would take place. The score of all the normal subjects and PD patients were 25 points or above by Mini-Mental State Examination. WCST in stage I PD patients (mean age 60.8, n = 9) was essentially same as those of young normal (mean age 23.1, n = 9) and adult normal (mean age 61.5, n = 10) subjects. Elderly normal subjects (mean age 75.8, n = 4) showed a significantly lower mean category achievement score (3.0 as the mean score) and higher numbers of errors and perseverations compared with those of young and adult normal subjects. Stage II (mean age 62.6, n = 8) and III PD (mean age 62.9, n = 8) patients showed significantly lower mean category achievement scores (2.4 and 2.1, respectively as the mean scores) and higher numbers of errors and perseverations compared with those of adult control subjects (5.4 as a mean score). TMT (B-A) in elderly normal subjects revealed significantly longer score (209 seconds as the mean score) compared with those of young and adult normal subjects (20 and 45 seconds, respectively as the mean scores). TMT (B-A) in stage III PD patients was significantly longer (219 seconds) compared with that of adult normal subjects (45 seconds as the mean), however TMT (B-A) in stage II PD patients (102 seconds as the mean) did not show prolongation. TMT (B/A) showed essentially similar results as TMT (B-A), however, stage II PD patients showed significant prolongation compared with that of normal adult subjects. Therefore, TMT (B/A) appears to be a more sensitive indicator of decline in executive function in PD. Between WCST and TMT, the former appeared to be a more sensitive indicator. Our results indicate that the decline in executive function takes place in normal ageing. In PD, this decline starts much earlier than the normal subjects. The onset in this decline coincides with the stage of PD, in which bilateral symptoms start to present. Anatomo-chemical subsrate of cognitive decline in PD is still to be debated, however, we believe that involvement of nigro-caudatal projection is at least in part responsible, as nigroputaminal pathway is mainly involved in motor functions. We also point out the importance of age factor in the evaluation of cognitive-executive function in PD, as this function is age-dependent in normal subjects.
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PMID:[Executive function in Parkinson's disease]. 1167 56

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron-emission-tomography (PET) studies, net blood-brain clearance of [18F]-fluoro-l-DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood-brain clearance of FDOPA (K(in)(app)) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes-of-interest. The Wisconsin-Card-Sorting-Test (WCST), Stroop-Test, Trail-Making-Test (TMT-A/B), and Continuous-Performance-Test (CPT-M) had been administered previously to the same subjects. No correlation of K(in) (app) with perseverative errors in WCST or age could be found. However, there were significant positive correlations between the magnitude of K(in)(app) in caudate nucleus, putamen, and midbrain with performance of the TMT-B, CPT-M, and the Stroop test. Highest correlations were found between the time needed to perform the Stroop interference task and the K(in)(app) of striatal areas (Caudate nucleus: -0.780, P = 0.005; putamen: -0.870, P < 0. 001). Thus, the present findings reveal a strong correlation between dopamine synthesis capacity in striatum of healthy volunteers and performance of cognitive tasks linked to the prefrontal cortex.
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PMID:'Prefrontal' cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation. 1713 2

Neuropsychological deficits are commonly found to be part of depression in old age and might simultaneously represent early symptoms of dementia. We investigated the influence of depression on processing speed and executive function in subjects who did not develop dementia during the following 5 years to examine whether these neuropsychological dysfunctions are due to depression or are influenced by other causes (e.g., education, cerebral comorbidity). A total of 287 subjects aged 75 (mean: 75.76) were available for analyses. Processing speed was measured by the Trail Making Test-A, Executive Function by the Trail Making Test-B and Verbal Fluency. DSM-IV-criteria were used for diagnosing depression. Cerebral comorbidity (e.g., stroke, Parkinson's disease), sex, education, antidepressant, and/or benzodiazepine medication, and a history of depression were taken into account as covariates. Univariate analyses and multiple regression analyses were calculated. Higher education was strongly related to better performance in all three psychometric tests. Cerebral comorbidity significantly slowed TMT-A performance and reduced Verbal Fluency scores. In multiple regression analysis depression showed only a minor, slowing influence on TMT-A and TMT-B performance. Depression only had a minor influence on processing speed and executive function in this sample of nondemented subjects. By comparison, the influence of education and cerebral comorbidity was seen to be stronger.
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PMID:The influence of depression on processing speed and executive function in nondemented subjects aged 75. 2188 Jan 69

The field of proteomics is undergoing rapid development in a number of different areas including improvements in mass spectrometric platforms, peptide identification algorithms and bioinformatics. In particular, new and/or improved approaches have established robust methods that not only allow for in-depth and accurate peptide and protein identification and modification, but also allow for sensitive measurement of relative or absolute quantitation. These methods are beginning to be applied to the area of neuroproteomics, but the central nervous system poses many specific challenges in terms of quantitative proteomics, given the large number of different neuronal cell types that are intermixed and that exhibit distinct patterns of gene and protein expression. This review highlights the recent advances that have been made in quantitative neuroproteomics, with a focus on work published over the last five years that applies emerging methods to normal brain function as well as to various neuropsychiatric disorders including schizophrenia and drug addiction as well as of neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. While older methods such as two-dimensional polyacrylamide electrophoresis continued to be used, a variety of more in-depth MS-based approaches including both label (ICAT, iTRAQ, TMT, SILAC, SILAM), label-free (label-free, MRM, SWATH) and absolute quantification methods, are rapidly being applied to neurobiological investigations of normal and diseased brain tissue as well as of cerebrospinal fluid (CSF). While the biological implications of many of these studies remain to be clearly established, that there is a clear need for standardization of experimental design and data analysis, and that the analysis of protein changes in specific neuronal cell types in the central nervous system remains a serious challenge, it appears that the quality and depth of the more recent quantitative proteomics studies is beginning to shed light on a number of aspects of neuroscience that relates to normal brain function as well as of the changes in protein expression and regulation that occurs in neuropsychiatric and neurodegenerative disorders.
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PMID:Recent advances in quantitative neuroproteomics. 2362 23

The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson's disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and Addenbrooke's Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance, and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance, and gait. PD participants took longer on Trail Making Tests, CRT-Location, and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B, was associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD.
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PMID:Executive function and postural instability in people with Parkinson's disease. 2513 74

Previous research has shown that anxiety in Parkinson's disease (PD) is associated with freezing of gait (FOG), and may even contribute to the underlying mechanism. However, limited research has investigated whether PD patients with FOG (PD+FOG) have higher anxiety levels when compared directly to non-freezing PD patients (PD-NF) and moreover, how anxiety might contribute to FOG. The current study evaluated whether: (i) PD+FOG have greater anxiety compared to PD-NF, and (ii) anxiety in PD is related to attentional set-shifting, in order to better understand how anxiety might be contributing to FOG. In addition, we explored whether anxiety levels differed between those PD patients with mild FOG (PD+MildFOG) compared to PD-NF. Four hundred and sixty-one patients with PD (231 PD-NF, 180 PD+FOG, 50 PD+MildFOG) were assessed using the Freezing of Gait Questionnaire item 3 (FOG-Q3), Hospital Anxiety and Depression Scale (HADS), Digit Span Test, Logical Memory Retention Test and Trail Making Tests. Compared to PD-NF, PD+FOG had significantly greater anxiety (p<0.001). PD+MildFOG, however, demonstrated similar levels of anxiety as the PD+FOG. In all patients, the severity of anxiety symptoms was significantly correlated to their degree of self-reported FOG on FOG-Q3 (p<0.001) and TMT B-A (p=0.039). Similar results were found for depression. In conclusion, these results confirm the key role played by anxiety in FOG and also suggest that anxiety might be a promising biomarker for FOG. Future research should consider whether treating anxiety with pharmacological and/or cognitive behavioural therapies at early stages of gait impairment in PD may alleviate troublesome FOG.
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PMID:Anxiety is associated with freezing of gait and attentional set-shifting in Parkinson's disease: A new perspective for early intervention. 2751 41

Research on the implications of anxiety in Parkinson's disease (PD) has been neglected despite its prevalence in nearly 50% of patients and its negative impact on quality of life. Previous reports have noted that neuropsychiatric symptoms impair cognitive performance in PD patients; however, to date, no study has directly compared PD patients with and without anxiety to examine the impact of anxiety on cognitive impairments in PD. This study compared cognitive performance across 50 PD participants with and without anxiety (17 PDA+; 33 PDA-), who underwent neurological and neuropsychological assessment. Group performance was compared across the following cognitive domains: simple attention/visuomotor processing speed, executive function (e.g., set-shifting), working memory, language, and memory/new verbal learning. Results showed that PDA+ performed significantly worse on the Digit Span forward and backward test and Part B of the Trail Making Task (TMT-B) compared to the PDA- group. There were no group differences in verbal fluency, logical memory, or TMT-A performance. In conclusion, anxiety in PD has a measurable impact on working memory and attentional set-shifting.
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PMID:Cognitive Function in Parkinson's Disease Patients with and without Anxiety. 2780 Jan 80

Introduction: Hyperechogenicity of the substantia nigra (SN+) is a risk marker for Parkinson's disease (PD) which can be detected before the diagnosis. In healthy individuals, SN+ has been associated with slight deficits in specific cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic marker for PD. However, the pattern of cognitive deficits associated with SN+ has not yet been compared with those present in PD. Methods: Data of 262 healthy individuals with normal echogenicity (SN-) and 48 healthy individuals with SN+ were compared with 82 early stage PD patients using the "Consortium to Establish a Registry for Alzheimer's disease" test battery. First, the test clusters (factors) were identified using a principal component analysis (PCA). Mean group performance of cognitive tests belonging to distinct factors, according to the PCA, and single subtest performances were compared using analyses of variance. Second, the number of individuals with abnormal cognitive performances (z-score < -1.0) were compared between groups. Results: Verbal memory, semantic and executive function, and praxis were identified as components of cognitive performances. The SN+ group performed significantly worse than the SN- group in tests assessing semantic and executive function, with a non-significant decrease in verbal memory. On the subtest level, individuals of the SN+ group scored significantly lower than the SN- group on the Boston Naming Test (BNT; p = 0.008). In all subtests, the percentages of PD patients with values below the cut-off for abnormal performance were higher than in the SN- group. Moreover, more individuals from the SN+ group scored below the cut-off in the BNT (SN- = 8.4%, SN+ = 20.8%, p = 0.01) and TMT-B (SN- = 6.9%, SN+ = 16.7%, p = 0.02), compared to the SN- group. Conclusion: This study confirms poorer performance of healthy individuals with SN+ compared to SN- in specific cognitive domains. However, against the SN- group, the cognitive profile of the SN+ group was not fully consistent with the profile of early PD patients. Our data argues that cognitive impairment associated with SN+ might differ slightly from that seen in early PD. Compensational mechanisms in the early phases of neurodegeneration, and the fact that only a subgroup of SN+ will develop PD, may partly explain these differences.
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PMID:Cognitive Performance Patterns in Healthy Individuals with Substantia Nigra Hyperechogenicity and Early Parkinson's Disease. 2789 78


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