UMLS:C0030567 - FACTA Search

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Query: UMLS:C0030567 (Parkinson's disease)
63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the extent to which depression complicates Parkinson's disease (PD), the authors analyzed the literature on depression in PD in order to report on its prevalence, clinical manifestations, and treatment. By means of MEDLINE literature searches, the analysis focused on 45 PD depression studies conducted from 1922 through 1998. The results indicate that the prevalence of depression is 31% for all PD patients. The clinical manifestations of PD depression include apathy, psychomotor retardation, memory impairment, pessimism, irrationality, and suicidal ideation without suicidal behavior. PD depression is effectively treated with a variety of antidepressants, most commonly at present the selective serotonin reuptake inhibitors. Anecdotal evidence supports the use of sertraline to treat PD depression.
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PMID:Prevalence, clinical manifestations, etiology, and treatment of depression in Parkinson's disease. 1144 25

The objective of the present investigation was to test the effects of benserazide/L-dopa treatment in a model of learning and memory deficits associated with early Parkinson's disease. Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a lesion in the substantia nigra, compact part and a specific loss of dopamine (DA) and its metabolites in the striatum of rats and a memory impairment in the two-way active avoidance task. The administration of benserazide/L-dopa (50 and 200 mg/kg) to the MPTP-lesioned rats restored the striatal level of DA, but did not reverse the MPTP-induced learning and memory impairment. As this treatment caused a large increase of DA levels in extrastriatal brain regions of the MPTP-lesioned animals, this study suggests that benserazide/L-dopa therapy was not effective in improving the observed learning impairment because this treatment appears to tilt the balance between DA levels in the striatum and in the extrastriatal regions, such as frontal cortex and limbic structures, resulting in a cognitive deficit.
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PMID:L-Dopa restores striatal dopamine level but fails to reverse MPTP-induced memory deficits in rats. 1180 61

Insulin resistance is known to play a pivotal role in type 2 diabetes. Senile individuals, besides being prone to insulin resistance and, consequently, to type 2 diabetes, manifest diseases of the central nervous system (CNS) that may be influenced by disturbances of insulin signaling in the brain, such as memory impairment, Parkinson disease, and Alzheimer disease. We investigated the expression and response to insulin of elements involved in the insulin-signaling pathway in the forebrain cortex and cerebellum of rats ages 1 d to 60 wk. The protein content of insulin receptors and SRC homology adaptor protein (SHC) did not change significantly along the time frame analyzed. However, insulin-induced tyrosine phosphorylation of the insulin receptor and SHC, and the association of SHC/growth factor receptor binding protein-2 (GRB2) decreased significantly from d 1 to wk 60 of life in both types of tissues. Moreover, the expression of SH protein tyrosine phosphatase-2 (SHP2), a tyrosine phosphatase involved in insulin signal transduction and regulation of the insulin signal, decreased significantly with age progression, in both the forebrain cortex and the cerebellum of rats. Thus, elements involved in the insulin-signaling pathway are regulated at the expression and/or functional level in the CNS, and this regulation may play a role in insulin resistance in the brain.
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PMID:Effects of age on elements of insulin-signaling pathway in central nervous system of rats. 1195 67

1. In this article we review the studies of memory disabilities in a rat model of Parkinson's disease (PD). 2. Intranigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rats causes a partial lesion in the substantia nigra, compact part (SNc) and a specific loss of dopamine and its metabolites in the striatum of rats. 3. These animals present learning and memory deficits but no sensorimotor impairments, thus modeling the early phase of PD when cognitive impairments are observed but the motor symptoms of the disease are barely present. 4. The cognitive deficits observed in these animals affect memory tasks proposed to model habit learning (the cued version of the water maze task and the two-way active avoidance task) and working memory (a working memory version of the water maze), but spare long-term spatial memory (the spatial reference version of the Morris water maze). 5. The treatment of these animals with levodopa in a dose that restores the striatal level of dopamine does not reverse these memory impairments, probably because this treatment promotes a high level of dopamine in extrastriatal brain regions, such as the prefrontal cortex and the hippocampus. 6. On the other hand, the adenosine receptor antagonist, caffeine, partly reverse the memory impairment effect of SNc lesion in these rats. This effect may be due to caffeine action on nigrostriatal neurons, since it induces dopamine release and modulates the interaction between adenosine and dopamine receptor activity. 7. These results suggest that the MPTP SNc-lesioned rats are a good model to study memory disabilities related to PD and that caffeine and other selective A(2A) adenosine receptor antagonists are promising drugs to treat this symptoms in PD patients.
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PMID:The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities. 1246 66

Neurodegenerative disorders such as Alzheimer's disease, Lewy-Body dementia, Parkinson's disease and cerebrovascular dementia result in an insidious cognitive and behavioural decline culminating in the development of severe dementia. Based on current population projections it has been estimated that by 2050 the number of individuals over 65 will increase to 1.1 billion worldwide and as a consequence, the number of cases of dementia to 37 million. Faced with such an enormous public health and socio-economic burden it is evident that the importance of therapeutic intervention aimed at either finding a cure or preventing disease progression cannot be overstated. The aim of the present paper is to present an overview, in the context of a brain aging continuum, at what stage cognition enhancing and/or neuroprotective intervention strategies aimed at stabilising and/or preventing neurodegenerative disease could demonstrate potential clinical benefit. In particular, the clinical identification of patients with mild cognitive impairment and age-associated memory impairment which may represent a 'transition' state between normal aging and dementia is discussed as a potential clinical population cohort targeted for early intervention in dementia. Considering the wide spectrum of cognitive and psychotic effects in dementia juxtaposed with the neuropathological evolution of the disease, it is clear that a variety of therapeutic intervention(s) will be required in order, to at the least, stabilise disease progression. Evidently, since Alzheimer's disease is by far the most prevalent form of dementia, and will undoubtedly serve as the benchmark for any future treatment of dementia, an update of current symptomatic and disease-modifying therapeutic approaches (cholinergic, glutamatergic, nootropics, beta-amyloid cascade inhibitors) will be reviewed.
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PMID:Cognition enhancing or neuroprotective compounds for the treatment of cognitive disorders: why? when? which? 1254 69

Cognitive decline, commonly first recognized as memory impairment, is a typical feature of Alzheimer's disease (AD). Neuropathological changes in the cerebral cortex and limbic system lead to deficits in learning, memory, language, and visuospatial skills. The precise nature of cognitive dysfunction reflects the distribution of pathological changes in AD. These will vary along the disease severity continuum and may also depend on where the disease sits in the spectrum of dementia. For example, AD-related disorders such as Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) also show symptoms of cognitive decline and share several pathological features, including degeneration of cortical cholinergic and striatal dopaminergic neurons. In vascular dementia (VaD), there is often an unequal distribution of cognitive deficit, with severe impairment in some functions and relative sparing of others. Cholinesterase (ChE) inhibitors, which help restore acetylcholine levels in the brain, are licensed for the symptomatic treatment of AD and have shown additional benefit in related dementias. Physiological correlates of cholinergic function/dysfunction in the brain include regional cerebral blood flow, glucose metabolism, and cerebrospinal fluid levels of ChE enzymes. These variables represent valuable markers of the clinical efficacy of ChE inhibitors. However, direct assessment of cognitive improvement, stabilization or decline is usually considered the key efficacy parameter in clinical studies of ChE inhibitors in AD and related dementias. Large-scale, placebo-controlled clinical studies of ChE inhibitors have demonstrated efficacy in treating the cognitive impairments associated with AD. Randomized comparative studies of ChE inhibitors are now under way to directly compare symptomatic efficacy and effects on disease progression. Clinical trial data of the cognitive effects of ChE inhibitors in AD, LBD, PDD, and VaD are discussed in detail in this article. The benefits of long-term treatment on symptomatic improvement in cognition and further potential disease-modifying effects are highlighted.
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PMID:The ABC of Alzheimer's disease: cognitive changes and their management in Alzheimer's disease and related dementias. 1263 80

A growing body of evidence suggests that the various cognitive symptoms found in Parkinson's disease (PD) are secondary to executive dysfunction. Studies addressing this possibility for memory impairment specifically have not included measures of working memory nor have they ruled-out potential mediating variables such as overall level of cognitive impairment or depression. The purpose of this study was to include measures of these variables in determining the relationship between multiple aspects of executive function and delayed verbal recall in 32 idiopathic PD patients. Results were consistent with the original hypothesis and further suggest that working memory is a key factor in recall memory and may mediate the relationship between other executive measures and recall in PD.
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PMID:The relationship between executive function and verbal memory in Parkinson's disease. 1290 79

To resolve differences in the literature, we have systematically reviewed 21 controlled comparisons of the cognitive performance of patients with dementia with Lewy bodies (DLB) These were identified by end May 2002 by Medline and PsycInfo searches, checking reference lists and contacting authors. Nine had comparisons between DLB patients (total n = 180) and age-matched controls (n = 172). Sixteen had comparisons between DLB (n = 312) and Alzheimer's disease (AD, n = 380). Three compared DLB (n = 48) with Parkinson's disease (PD, n = 65). Two raters independently scored the methodological quality. This was variable with a lack of high-quality studies (median rating 3 on a 0-7 scale, Kw = 0.41). There was a significant heterogeneity in results with marked discrepancies between studies. In a meta-analysis, DLB patients were more cognitively impaired than were AD or PD patients (95% CI of inverse variance weighted average of effect size relative to controls DLB 2.0-2.2; AD 1.4-1.6; PD 0.7-1.0). To permit an analysis of impairments in specific cognitive areas, the cognitive abilities underpinning the wide variety of tasks used were classified by a group of experienced neuropsychologists. Reducing overlapping task classifications using factor analysis showed large effect sizes relative to controls, AD and PD on two factors (combined variance 30%): attentional/executive impairment (effect sizes 1.1-2.9) and visual-perceptual impairment (0.7-3.6). There were small differences on two other factors (combined variance 39%): general verbal/non-verbal impairment (-0.12 to -0.5) and relative verbal memory impairment (-0.33 to 0.21). The cognitive performance is also more variable in DLB than in controls or in AD, but not PD (ratio of DLB to comparator standard deviations estimated from linear regression: DLB/controls 2.5-3.6; DLB/AD 2.1-2.6; DLB/PD 0.8-1.0). The greater variability of patients with DLB is seen only on tasks needing timed or motor responses, visual learning, executive or attentional abilities, or with visual content. Further stratification indicated that recent consensus diagnostic criteria, clinical diagnoses, and milder dementia were all associated with a more distinctive cognitive profile. The uniquely profound visual-perceptual and attentional-executive impairments that characterize DLB are consistent with the most frequent locations of Lewy bodies in frontal, cingulate, and inferior temporal cortex and may be related to the characteristic visual hallucinations and clinical fluctuations of this disease. These findings need to be confirmed in prospective, longitudinal, clinicopathological studies.
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PMID:Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia. 1451 18

The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. The results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals. The tested toxin reduced striatal dopamine levels in comparison to sham-operated and non-operated groups. A final surprising result was that phosphatidylserine was unable to reverse the cognitive deficits produced by MPTP or the reduction of striatal dopamine levels. In conclusion, the data suggest that MPTP is a good model to study the early impairment associated with Parkinson's disease and phosphatidylserine did not improve the memory impairment induced by MPTP.
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PMID:Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats. 1474 7

Glucocorticoid hormones are important in the maintenance of many brain functions. Although their receptors are distributed abundantly throughout the brain, including the prefrontal cortex (PFC), it is not clear how glucocorticoid functions, particularly with regard to cognitive processing in the PFC. There is evidence of PFC cognitive deficits such as working memory impairment in several stress-related neuropsychiatric disorders, including depression, schizophrenia, and Parkinson's disease. Disruption of the hypothalamo-pituitary-adrenal (HPA) system, which is characterized by attenuated glucocorticoid negative feedback, is also observed. In rats, chronic stress induces working memory impairment as a result of decreased dopaminergic transmission in the PFC. These chronically stressed rats also show HPA disruption; this is caused in part by a reduced glucocorticoid response in the PFC. These findings implicate reduced glucocorticoid actions in working memory impairment. In the present study, we examined the effects of the suppression of endogenous glucocorticoids by adrenalectomy (ADX) on working memory in rats and explored the involvement of PFC dopaminergic activities in memory. The ADX impaired working memory, decreased dopamine release, and upregulated D1 receptors in the PFC. These dysfunctions were prevented by corticosterone replacement that reproduced normal physiological plasma levels, indicating that suppression of glucocorticoids causes these dysfunctions. Moreover, the ADX-induced working memory impairment was ameliorated by intra-PFC infusions of a D1 receptor agonist, SKF 81297. Thus, suppression of glucocorticoids impaired working memory through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. This finding indicates that endogenous glucocorticoids are essential for maintaining PFC cognitive function and suggests that HPA disruption contributes to PFC cognitive deficits.
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PMID:Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function. 1520 21

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