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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 test the hypothesis that the cognitive impairments that accompany Parkinson's disease (PD) arise from frontal lobe dysfunction, patients with idiopathic PD and controls were tested on a neuropsychological battery that included measures of anterograde memory, visuospatial perception, and naming, as well as several tests that are known to be sensitive to lesions of the frontal lobes. PD patients of normal mental status as measured by the Mini-Mental State Examination performed normally on the naming, line orientation, and verbal recognition memory tests but exhibited deficits on verbal recall. On tests of frontal lobe function, these patients showed mild deficits on a category fluency task and on the Wisconsin Card Sorting Test. However, their errors on the latter were not typical of patients with frontal lesions, and they performed normally on a letter fluency task and exhibited normal release from proactive interference. Patients of lower than normal mental status performed poorly on nearly all of the cognitive tasks including confrontational naming, line orientation, and recognition memory, suggesting that their cerebral dysfunction extended beyond subcortical-frontal circuits. The present study supports the usefulness of the Mini-Mental State Examination for cognitive screening of PD patients, but does not support the hypothesis that the cognitive impairments in PD arise principally from disruption of frontal lobe functioning.
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PMID:Cognitive disturbances in Parkinson's disease. 274 31

Numerous homeostatic mechanisms regulate impulse traffic in the neural pathways of the brain. If, for whatever reason, these mechanisms are unable to maintain neural activity within normal levels, the resulting disruption of the balance of impulse traffic produces brain dysfunction such as mental or neurological disorders. Drug treatment of these disorders involves the use of agents that return impulse traffic to homeostatic levels. Such agents have been found only for certain disorders such as Parkinson's Disease, certain affective disorders and some aspects of schizophrenia. The development of therapeutic interventions for currently untreatable conditions such as Huntington's Chorea or Alzheimer's Disease and the design of drugs for the more efficient treatment of psychiatric disorders, would be greatly facilitated by more detailed knowledge of the specific homeostatic mechanisms controlling brain function.
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PMID:Neurochemical psychiatry as a source of hypotheses concerning the role of homeostatic mechanisms in brain function. 615 Sep 4

The purpose was to determine if unmedicated, mildly affected patients with Parkinson's disease exhibited abnormality in the P3 component of the event-related potential, and whether such abnormality differed between younger and older patients. The study evaluated 10 younger (mean age = 43.7 years) and 10 older (mean age = 64.4 years) unmedicated patient volunteers diagnosed with idiopathic PD during the past 4 years and equal numbers of age-, gender-, and education-matched controls. The auditory oddball P3 was recorded, and P3 peak amplitude, peak latency, and the component score derived from principal components analysis were analysed. Neuropsychological measures focusing on frontal lobe and memory function were obtained. Although patients did not show neuropsychological deficits, they had significantly enlarged P3 amplitude measured at Cz (p < 0.01) or Pz (p < 0.01). The P3 amplitude abnormality among patients was not affected by age. Patient P3 latency was not prolonged. The results indicate that P3 amplitude may more sensitive than neuropsychological measures for detecting subtle brain dysfunction occurring early in PD. This measure has possible utility for detecting and tracking early disease. It is hypothesized that enlarged P3 amplitude reflects abnormality in use of attentional resources to compensate for brain dysfunction.
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PMID:Event-related potential P3 change in mild Parkinson's disease. 877 Oct 65

Altered energy metabolism is characteristic of many neurodegenerative disorders. Reductions in the key mitochondrial enzyme complex, the alpha-ketoglutarate dehydrogenase complex (KGDHC), occur in a number of neurodegenerative disorders including Alzheimer's Disease (AD). The reductions in KGDHC activity may be responsible for the decreases in brain metabolism, which occur in these disorders. KGDHC can be inactivated by several mechanisms, including the actions of free radicals (Reactive Oxygen Species, ROS). Other studies have associated specific forms of one of the genes encoding KGDHC (namely the DLST gene) with AD, Parkinson's disease, as well as other neurodegenerative diseases. Reductions in KGDHC activity can be plausibly linked to several aspects of brain dysfunction and neuropathology in a number of neurodegenerative diseases. Further studies are needed to assess mechanisms underlying the sensitivity of KGDHC to oxidative stress and the relation of KGDHC deficiency to selective vulnerability in neurodegenerative diseases.
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PMID:The alpha-ketoglutarate dehydrogenase complex in neurodegeneration. 1067 73

Impairments of glucose and mitochondrial function are important causes of brain dysfunction and therefore of brain disease. Abnormalities have been found in association with disease of the nervous system in most of the components of glucose/mitochondrial metabolism. In many, molecular genetic abnormalities have been defined. Brain glucose oxidation is abnormal in common diseases of the nervous system, including Alzheimer disease and other dementias, Parkinson disease, delirium, probably schizophrenia and other psychoses, and of course cerebrovascular disease. Defects in a single component and even a single mutation can be associated with different clinical phenotypes. The same clinical phenotype can result from different genotypes. The complex relationship between biological abnormality in brain glucose utilization and clinical disorder is similar to that in other disorders that have been intensively studied at the genetic level. Genes for components of the pathways of brain glucose oxidation are good candidate genes for disease of the brain. Preliminary data support the proposal that treatments to normalize abnormalities in brain glucose oxidation may benefit many patients with common brain diseases.
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PMID:Glucose/mitochondria in neurological conditions. 1242 Mar 64

To better understand the pathogenesis of brain dysfunction in Gaucher disease (GD), we studied brain pathology in seven subjects with type 1 GD (four also exhibited parkinsonism and dementia), three with type 2 GD and four with type 3 GD. Unique pathologic patterns of disease involving the hippocampal CA2-4 regions and layer 4b of the calcarine cortex were identified. While these findings were common to all three GD phenotypes, the extent of the changes varied depending on the severity of disease. Cerebral cortical layers 3 and 5, hippocampal CA2-4, and layer 4b were involved in all GD patients. Neuronal loss predominated in both type 2 and type 3 patients with progressive myoclonic encephalopathy, whereas patients classified as type 1 GD had only astrogliosis. Adjacent regions and lamina, including hippocampal CA1 and calcarine lamina 4a and 4c were spared of pathology, highlighting the specificity of the vulnerability of selective neurons. Elevated glucocerebrosidase expression by immunohistochemistry was found in CA2-4. Hippocampal (45)Ca(2+) uptake autoradiography in rat brain was performed demonstrating that hippocampal CA2-4 neurons, rather than CA1 neurons, were calcium-induced calcium release sensitive (CICR-sensitive). These findings match recent biochemical studies linking elevated glucosylceramide levels to sensitization of CA2-4 RyaR receptors and 300% potentiation of neuronal CICR sensitivity. In two patients with type 1 GD and parkinsonism, numerous synuclein positive inclusions, similar to brainstem-type Lewy bodies found in Parkinson disease, were also found hippocampal CA2-4 neurons. These findings argue for a common cytotoxic mechanism linking aberrant glucocerebrosidase activity, neuronal cytotoxicity, and cytotoxic Lewy body formation in GD.
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PMID:Neuropathology provides clues to the pathophysiology of Gaucher disease. 1523 32

Alzheimer's and Parkinson's diseases are the most common neurodegenerative conditions. Oxidative lesions are a hallmark of both diseases, but the respective roles of systemic and cerebral dysfunction are not elucidated. As circulating neutrophils are the most powerful sources of reactive oxygen species, we measured oxidative stress levels in resting neutrophils from 44 Alzheimer's and Parkinson's disease patients and compared them to 40 healthy counterparts. Significantly increased oxidative stress levels were observed in patients' groups, while control groups had very similar levels irrespective of age. One-third of the neurodegenerative patients presented with oxidative stress levels higher than those of any healthy donor. This increase was not due to an elevated production of reactive oxygen species during the neutrophil oxidative burst. Mitochondrial mass and activity were altered in neutrophils of the Parkinsonian group compared to controls, but not in those from Alzheimer's disease group. To our knowledge, this is the first report linking oxidative stress and mitochondrial parameters in circulating neutrophils from neurodegenerative and normal donors. Our results indicate that oxidative stress levels in circulating neutrophils are of interest for further mechanistic studies of neurodegenerative diseases and might open the perspective of a diagnostic tool.
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PMID:Oxidative stress level in circulating neutrophils is linked to neurodegenerative diseases. 1562 53

Neuropsychiatry represents a field of medicine situated at the crossroads of neurology and psychiatry, and deals with the interface of behavioral phenomena driven by brain dysfunction. Psychiatric symptoms are highly prevalent in these conditions, are a major source of disability and diminished quality of life, and potentially represent the target of treatment interventions that stand to significantly decrease the suffering they generate. In this article, the disease paradigm is explained, with particular attention to its role as an organizing principle for the field. Specific diseases including traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy are explored in relation to the presentation of multiple psychiatric phenotypes in each, associations with underlying brain pathology, and existing treatment approaches. Finally the article explores the inherent complexities in this area of research and proposes a framework for future work based on the understanding of phenomenology and associated risk factors, the involvement of the rapidly advancing field of neuroscience, and targeted treatment development to serve as a road map for advancement in the field..
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PMID:Psychiatric manifestations of neurologic disease: where are we headed? 1772 11

There are recent reports that alexithymia may be associated with brain dysfunction involving frontal lobes or right hemisphere regions. However, little is known about the relationship between alexithymia and cognitive deficits in Parkinson's disease (PD). The authors investigated the neuropsychological correlates of alexithymia in a population of 70 nondemented PD patients and 70 controls. Alexithymia was screened using the 20-item version of the Toronto Alexithymia Scale (TAS-20). Standardized scales that measure verbal episodic memory, executive functions, abstract reasoning, and visual-spatial and language abilities were adopted. PD patients with alexithymia performed worse than both PD patients without alexithymia and controls with or without alexithymia on tasks requiring visual-spatial processing. Moreover, regression analyses showed that, in PD patients, but not in controls, poor performance on a constructional praxis task predicted high scores on the TAS-20 subscale, which assesses difficulty in identifying emotions. These data evidence an association between alexithymia and visual-spatial processing alterations in PD patients, supporting the view that the right hemisphere could be specifically involved in the modulation of some facets of alexithymia.
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PMID:Neuropsychological correlates of alexithymia in Parkinson's disease. 1794 16

Medical therapies targeting infections and neoplasms often involve a multi-pronged strategy sometimes called "rational poly-pharmacy", while other disorders such as Parkinson's disease emphasize targeting a single neurotransmitter system (dopamine). Although the clinical literature favors a "serotonin hypothesis" for depression, a growing basic science literature suggests that selective serotonin reuptake inhibitors (SSRIs) directly modulate neurotransmitter- and voltage-gated neuronal ion channels. In addition, biosynthesis of neurosteroids (themselves promiscuous ion channel modulators), is activated by SSRIs. These non-canonical effects are entirely independent of serotonin signaling, and they occur in the range of SSRI concentrations reported in the brains of treated patients (1-10 microM). The protean impact of these diverse channel targets on neuronal excitability raises interesting and potentially testable hypotheses about depression pathophysiology and treatment. Specifically, emerging network theories are embracing the non-linearity and complexity of brain circuitry and its oscillatory behavior, with clinical correlations in psychiatry and neurology. Is it possible that certain brain dysfunction (such as depression) may be more amenable to a poly-pharmacy approach? The promiscuity of SSRIs suggests that such poly-pharmacy can emerge from a single agent.
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PMID:Non-serotonin anti-depressant actions: direct ion channel modulation by SSRIs and the concept of single agent poly-pharmacy. 1803 42


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