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)

Idiopathic Parkinson's disease (IPD) has been subclassified on the basis of predominant motor symptomatology, age at disease onset, depressive affect, and cognitive performance. However, subgroups are usually arbitrarily defined and not reliably based on qualitatively distinct neuropathology. We explored heterogeneity in IPD in a data-driven manner using comprehensive demographic, motor, mood, and cognitive information collected from 176 patients with IPD. Cluster analysis revealed three subgroups of patients at a disease duration of 5.6 years and two subgroups at 13.4 years. The subgroups may represent the clinical progression of three distinct subtypes of IPD. The "motor only" subtype was characterized by motor symptom progression in the absence of intellectual impairment. Equivalent motor symptom progression was shown by the "motor and cognitive" subtype which was accompanied by executive function deficits progressing to global cognitive impairment. The "rapid progression" subtype was characterized by an older age at disease onset and rapidly progressive motor and cognitive disability. There was no relationship between the motor and cognitive symptoms in any subtype of IPD. We conclude that the clinical heterogeneity of IPD is governed by distinct neuropathologic processes with independent etiologic influences.
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PMID:A data-driven approach to the study of heterogeneity in idiopathic Parkinson's disease: identification of three distinct subtypes. 991 39

Intravenous application of amantadine sulphate induces a rapid improvement of motor symptoms in Parkinson's disease (PD), but there are no trials on the efficacy of this compound on bradykinesia, rigidity and tremor in detail in combination with standardized instrumental measurement of tapping and peg insertion abilities. We treated 31 stable non fluctuating PD patients with amantadine, scored motor symptoms of both arms and performed peg insertion and tapping under cued conditions before and after 3 days. Motor symptoms and peg insertion significantly improved in contrast to tapping. Tapping asks for repetitive performance of simple standardized movements, therefore it needs low cognitive efforts. Since peg insertion depends on more complex movements and thus more dopamine dependent cognitive processes, it improved after application of the indirect dopaminomimetic substance amantadine.
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PMID:Intravenous amantadine sulphate application improves the performance of complex but not simple motor tasks in patients with Parkinson's disease. 1261 92

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.
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PMID:Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study. 1282 92

This study evaluated the frequency of obsessive-compulsive disorder (OCD), obsessive-compulsive symptoms (OCS), and related disorders (e.g., tic disorders, trichotillomania, and body dysmorphic disorder) in 100 patients with Parkinson's disease (PD) and 100 individually matched controls. When compared with controls, OCD, OCS, and related disorders were not higher in PD. Findings revealed an association of some OCS with left side motor symptom predominance in PD patients, particularly for symmetry and ordering/arranging. These findings suggest that the right hemisphere likely functions in the expression of OCS.
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PMID:Obsessive-compulsive symptoms, obsessive-compulsive disorder, and related disorders in Parkinson's disease. 1292 16

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called "conflict of paradigms." Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting "horizontal modulation" of cortico-cortical relation. Furthermore, alteration in "top-down modulation" reflecting "vertical modulation" of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered "bottom-up modulation" between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation--"vertical" and "horizontal" modulation, respectively.
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PMID:What catatonia can tell us about "top-down modulation": a neuropsychiatric hypothesis. 1295 42

During the past decade, dopamine transporter (DAT) imaging with single photon emission computerized tomography (SPECT) or positron emission tomography (PET) has evolved as an objective in vivo marker of nigrostriatal neuron loss in Parkinson's disease (PD). We investigate the relationship between striatal DAT binding, measured with [(123)I]beta-CIT SPECT, and parkinsonian motor handicap in a sample of 59 PD patients with minimal to severe disability, and review published cross-sectional studies on the correlation between DAT imaging and motor symptoms in PD. Earlier studies as well as the present results show a good correlation between overall striatal DAT binding and global measures of disease severity such as the Hoehn and Yahr scale, the total score on the Unified Parkinson's Disease Rating Scale (UPDRS), and UPDRS activities of daily living, with a progressive decline of DAT binding with increasing disability. A number of studies found a significant inverse correlation of striatal DAT binding with UPDRS motor score. Bradykinesia, posture, gait, and other midline symptoms, such as speech and facial expression, compared with rigidity, seem to be more closely related to striatal DAT binding. By contrast, neither the severity of parkinsonian rest nor of action tremor is related to the degree of dopaminergic denervation as measured by DAT imaging. Motor symptoms in the clinically less affected body side show a closer correlation with striatal DAT binding than do symptoms occurring in the dominantly affected body side. The correlation of putamen and caudate DAT binding with parkinsonian motor handicap seems to be similar. Although there have been limited comparative studies applying [(18)F]fluorodopa PET and DAT imaging in the same group of PD patients, available data suggest that putamen [(18)F]fluorodopa uptake, when compared with striatal DAT binding, may be more closely related to parkinsonian motor handicap.
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PMID:Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it? 1453 Oct 46

The relationship between dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) has been insufficiently described, and it is still problematic. Twenty-nine cases of DLB and 10 cases of PDD were investigated in the present study. DLB cases disclosed a significantly older disease onset and shorter disease duration than PDD cases (p<0.01 each). However, they showed no significant difference in dementia onset or dementia duration (p>0.05 each). Motor symptoms (parkinsonism) were suspected as the cause of the younger disease onset in PDD cases. Compared with 10 age-matched cases of definite Alzheimer's disease, both 19 DLB cases and 6 PDD cases had significantly better scores in the final test of mini-mental state examination (MMSE) and revised version of Hasegawa's Dementia Scale (HDSR) within 12 months before death, although no significant differences between DLB and PDD were indicated. DLB and PDD were suspected to show cognitive impairment of similar severity in the terminal stage. They would thus be difficult to classify as completely different entities.
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PMID:Cognitive conditions of pathologically confirmed dementia with Lewy bodies and Parkinson's disease with dementia. 1460 10

Research and development of the adenosine A2A receptor selective antagonist KW6002 have focused on developing a novel nondopaminergic therapy for Parkinson's disease (PD). Salient pharmacologic features of KW6002 were investigated in several animal models of PD. In rodent and primate models, KW6002 provides symptomatic relief from parkinsonian motor deficits without provoking dyskinesia or exacerbating existing dyskinesias. The major target neurons of the A2A receptor antagonist were identified as GABAergic striatopallidal medium spiny neurons. A possible mechanism of A2A receptor antagonist action in PD has been proposed based on the involvement of striatal and pallidal presynaptic A2A receptors in the "dual" modulation of GABAergic synaptic transmission. Experiments with dopamine D2 receptor knockout mice showed that A2A receptors can function and anti-PD activities of A2A antagonists can occur independent of the dopaminergic system. Clinical studies of KW6002 in patients with advanced PD with L-dopa-related motor complications yielded promising results with regard to motor symptom relief without motor side effects. The development of KW6002 represents the first time that a concept gleaned from A2A biologic research has been applied successfully to "proof of concept" clinical studies. The selective A2A antagonist should provide a novel nondopaminergic approach to PD therapy.
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PMID:Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor selective antagonist KW6002: research and development toward a novel nondopaminergic therapy for Parkinson's disease. 1466 20

Motor symptoms of Parkinson's disease (PD) are substantially improved by bilateral high-frequency electrical stimulation of the subthalamic nucleus (STN). Altered cerebral blood flow (CBF) in a network of frontal cortical and subcortical structures has been reported in numerous studies of patients undergoing subthalamic stimulation. However, CBF is a controversial indicator of brain activation because measures of blood flow bear a variable relation to measures of brain work and energy metabolism. We hypothesized that STN stimulation would alter the rate of oxygen consumption (CMRO(2)) in cerebral cortical areas in proportion to previously reported changes in CBF in patients undergoing stimulation at rest. We used quantitative PET to map CMRO(2) in brain of seven patients with Parkinson's disease, first in a baseline condition with pause of stimulation and medication for a period of 12 h, and again after 4 h of stimulation. Comparison of these two conditions revealed activation of CMRO(2) in the cerebellum, and in specific posterior neocortical regions, most notably in the left lingual gyrus and in the right lateral occipitotemporal gyrus, both of which latter regions are linked to higher-order visual processing. CMRO(2) was unaffected in the frontal cortex. Thus, the present findings do not support the original hypothesis, but suggest that STN stimulation increases energy metabolism in the posterior cerebral cortex, especially in regions involved in perception of movement and the direction of movement to visual cues.
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PMID:Focal changes of oxygen consumption in cerebral cortex of patients with Parkinson's disease during subthalamic stimulation. 1519 28

Chronic subthalamic nucleus stimulation produces inconsistent patterns of cognitive change in Parkinson's disease patients. Individually tailored stimulation parameters may contribute to this variable pattern of change. Systematic variation of amplitude, pulse width, and rate of stimulation has been reported to produce unique changes in motor and limbic response. To evaluate the association between stimulation parameters and cognitive/behavioral response, neuropsychological performance and stimulation parameter data of 8 Parkinson's disease patients were submitted to Pearson r correlation analysis. Results indicate that each stimulation parameter was significantly associated with a subset of measures. The current findings raise the possibility that adverse cognitive/behavioral responses may be treated through parameter modification while maintaining motor symptom efficacy.
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PMID:Deep brain stimulation for Parkinson's disease: association between stimulation parameters and cognitive performance. 1555 68


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