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

Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED) PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0-16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultaneous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.
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PMID:A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. 338 17

Groups of patients with idiopathic Parkinson's disease (PD), either medicated or unmedicated, were compared with matched groups of normal controls on a computerised battery of tests designed to investigate spatial working memory, visuospatial recognition memory and learning. The medicated PD patients were subdivided into those with mild and severe clinical disability on the basis of Hoehn and Yahr ratings, thus making three groups of PD patients in all. In a test of spatial recognition memory, a significant impairment was only evident in those PD patients who were medicated and had severe clinical symptoms (Hoehn and Yahr stage III-IV). In contrast, none of the three patient groups were impaired in a complementary test of visual pattern recognition memory. Whilst all three patient groups performed well in a test of simultaneous visual matching to sample, medicated patients (MED PD) with severe clinical symptoms were significantly impaired when a short (0-12 sec) delay was introduced. In a test of paired associates learning requiring both visual pattern and visuospatial memory, deficits in learning and memory were only evident in the severely impaired MED PD group. In contrast, in a test of spatial working memory known to be sensitive to frontal lobe damage, significant impairments were found in both groups of medicated PD patients and particularly in those patients with more severe clinical symptoms. Taken together, the results suggest that there are multiple memory impairments in PD which may differentially depend on the clinical severity of the disease.
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PMID:Visuospatial memory deficits at different stages of Parkinson's disease. 837 37

A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.
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PMID:Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists. 1832 69

"Pulsatile" administration of levodopa has been invocated a relevant factor for motor fluctuations in Parkinson's disease (PD). We studied dopaminergic sensitivity to apomorphine in 10 parkinsonian patients with motor fluctuations. Patients were tested as follows: the minimal effective dose of apomorphine (MED-1) was administered in the morning to induce an on response. Fifteen minutes after this motor response had disappeared, an apomorphine infusion was initiated and maintained to ensure on periods of three different durations on different days. Infusion lasted for approximately 30, 60 and 90 minutes. Subsequently, the infusion was stopped, and after 15 minutes in the off state, a second bolus of apomorphine (MED-2) was given. The mean infusion doses were 49.2 +/- 5.4, 108.4 +/- 10.3, and 150 +/- 8.2 mg. These elicited on periods of 48.2 +/- 4.1, 110 +/- 4.5, and 195 +/- 3.8 minutes. The MED-2 elicited on responses with a duration of 30 +/- 4.5, 18.4 +/- 3.2, and 11.2 +/- 4.1 minutes. The duration of the on response induced by the apomorphine infusions correlated inversely (P < 0.01) with the on induced by the MED-2 of apomorphine. Our findings indicate that a continuous dopaminergic stimulus may induce pharmacodynamic changes associated with tolerance in PD patients.
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PMID:The duration of the motor response to apomorphine boluses is conditioned by the length of a prior infusion in Parkinson's disease. 2022 30

This narrative review examines the effects of drug therapy on the natural history of Parkinson's disease. In terms of modifying the underlying disease process, it is possible that immediate therapy, rather than deferred treatment, can have a positive effect on the underlying disease process. However, it is unlikely that drug therapy has changed mortality from the condition and there is no evidence that it can delay the onset of non-motor features such as dementia and falls. The beneficial effects of drug therapy on the motor symptoms of Parkinson's disease are unquestionable, but these are at the expense of short-term dopaminergic side effects, long-term motor complications, and impulse control disorders. Major questions remain regarding which initial therapeutic approach should be taken which may possibly be answered by the ongoing PD MED trial. The beneficial effects of drug therapy on the motor features of Parkinson's disease have had a fundamental impact on the suffering of patients. The mainstay of these therapies continues to be levodopa, although it is now used at lower doses than in the past and in combination with other drug classes.
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PMID:Has drug therapy changed the natural history of Parkinson's disease? 2108 Jan 87

At odd with traditional views, effective sub-thalamic nucleus (STN) deep brain stimulation (DBS), in Parkinson's disease (PD) patients, may increase the discharge rate of the substantia nigra pars reticulata and the internal globus pallidus (GPi), in combination with increased cyclic guanosine monophosphate (cGMP) levels. How these changes affect the basal ganglia (BG) output to the motor thalamus, the crucial structure conveying motor information to cortex, is critical. Here, we determined the extracellular GABA concentration in the ventral anterior nucleus (VA) during the first delivery of STN-DBS (n=10) or following levodopa (LD) (n=8). Both DBS and subdyskinetic LD reversibly reduced (-30%) VA GABA levels. A significant correlation occurred between clinical score and GABA concentration. By contrast, only STN-DBS increased GPi cGMP levels. Hence, STN-ON and MED-ON involve partially different action mechanisms but share a common target in the VA. These findings suggest that the standard BG circuitry, in PD, needs revision as relief from akinesia may take place, during DBS, even in absence of reduced GPi excitability. However, clinical amelioration requires fast change of thalamic GABA, confirming, in line with the old model, that VA is the core player in determining thalamo-cortical transmission.
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PMID:The clinical efficacy of L-DOPA and STN-DBS share a common marker: reduced GABA content in the motor thalamus. 2154 93

Reversal learning (RL) has been widely used for assessment of behavioral adaptation, impulsivity, obsession, and compulsion in healthy controls as well as people suffering from psychiatric and neurological disorders such as Parkinson's disease (PD). Nevertheless, studies addressing high cognitive functions such as metacognition in PD are scarce. Here, we address for the first time the effect of levodopa and PD on metacognition within the framework of a RL paradigm. In agreement with previous reports, PD patients exhibited reversal shifting impairment with respect to healthy controls (CTRL) regardless of medication condition (MED-ON and MED-OFF), which was supported by a well-known model of learning conditioning (Rescorla-Wagner). In spite that we found a significant association between accuracy and decision confidence level for MED-OFF and CTRL, analysis of metacognitive sensitivity assessed by type 2 signal detection theory (SDT) revealed only a significant underperformance for patients without medication (MED-OFF). This finding points toward a non-compromising positive effect of dopaminergic medication on metacognition for PD.
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PMID:Assessment of Metacognition and Reversal Learning in Parkinson's Disease: Preliminary Results. 3025 76

Debate is ongoing regarding when, why, and how to initiate pharmacotherapy for Parkinson's disease. Early initiation of dopaminergic therapies does not convey disease-modifying effects but does reduce disability. Concerns about the development of motor complications arising from the early initiation of levodopa, which led to misconceived levodopa-sparing strategies, have been largely mitigated by the outcomes of the PD MED and Levodopa in Early Parkinson's Disease (LEAP) studies. The LEAP study also showed the potential for early improvement in quality of life, even when disability is negligible. Until more effective methods of providing stable dopamine concentrations are developed, current evidence supports the use of levodopa as initial symptomatic treatment in most patients with Parkinson's disease, starting with low doses and titrating to therapeutic threshold. Monoamine oxidase-B inhibitors and dopamine agonists can be reserved as potential adjunct treatments later in the disease course. Future research will need to establish effective disease-modifying treatments, address whether patients' quality of life is substantially improved with early initiation of treatment rather than a wait and watch strategy, and establish whether new levodopa formulations will delay onset of dyskinesia.
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PMID:Initiation of pharmacological therapy in Parkinson's disease: when, why, and how. 3217 87

To review and systematically summarize the psychometric and clinical properties (reliability, validity, responsiveness) of the Timed Up and Go test applied to persons diagnosed with Parkinson disease. A systematic review was performed by screening four scientific databases (MED-LINE, CINAHL, and PubMed). Independent reviewers selected and extracted data from articles that assessed the reliability, validity, sensitivity to change, and/or clinical properties of the Timed Up and Go test in persons with Parkinson disease. Twenty-four studies were selected. Nine analyzed reliability and yielded "good" to "moderate" scores. Seventeen used a range of different contrast tests to assess validity of the Timed Up and Go test and found "good" quality scores in those that assessed balance. Only two studies analyzed sensitivity to change and they reported "poor" quality scores. The use of Timed Up and Go in Parkinson disease patients presents good reliability and validity (when compared to tests that assess balance).
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PMID:Evaluation of the psychometric properties and clinical applications of the Timed Up and Go test in Parkinson disease: a systematic review. 3291 35