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)

Impairment in different cognitive domains such as executive functions, language, memory, and visuospatial skills occurs frequently in Parkinson disease (PD) even in the early stages of the disease. Although frank dementia (Parkinson disease dementia, PDD) is less frequent, risk for developing dementia is two to six times greater than the prevalence rate in general population and it increases in relation to disease duration. Clinically, dementia in PD is characterized by uninsidious onset and slowly progressive cognitive decline, with a predominant dysexecutive syndrome accompanied frequently by a variety of behavioral symptoms such as hallucinations, depression, anxiety, and excessive daytime sleepiness. Although the exact pathophysiology and neurobiological basis of PDD is not known, dementia in PD probably develops as a result of progressive involvement of subcortical and cortical structures by Lewy-type pathology and associated Alzheimer-like histological changes. Dysfunction of different monoamine transmitter has also been implicated in the cognitive deterioration of PD but reduced cholinergic activity in the cortex is thought to account for the strongest mechanism in the development of dementia. Recent evidence suggests that cholinesterase inhibitors are effective in the treatment of dementia and accompanying behavioral symptoms in PD.
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PMID:Cognitive dysfunction and dementia in Parkinson disease. 1817 97

The history of dementia with Lewy bodies (DLB) was introduced. In 1976 we reported our first autopsied case with "diffuse Lewy body disease (DLBD)", the term of which we proposed in 1984. In addition, we reported, for the first time, the detailed characteristics and distribution pattern of cortical Lewy bodies, based on our own three autopsied DLBD cases, in 1978. We also reported two German autopsied cases with DLBD in 1979, which were the first DLBD cases reported in Europe. In 1980 we proposed the term "Lewy body disease" and classified it into three types: a brain stem type, a transitional type and a diffuse type. The brain stem type is equal to Parkinson disease (PD), and the diffuse type was later designated as DLBD. Furthermore, we reviewed all DLBD cases reported in Japan and classified DLBD into two forms: a common form with more or less Alzheimer pathology and a pure form without it. Since then we have reported many papers concerning DLBD. Based on our reports the term "dementia with Lewy bodies" was proposed at the first international workshop in 1995. The CDLB guidelines were published in 1996, and the CDLB guidelines--revised were also reported in 2005. In the revised guidelines the term "Lewy body disease" was used as the generic term including DLB, PD and PDD as we had insisted since 1980.
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PMID:[Dementia with Lewy bodies--from its finding to the present, including the CDLB guideline-revised]. 1821 Jul 80

Dementia is common in Parkinson disease (PD), although its anatomic and pathologic substrates remain undefined. Recently, striatal abnormalities in Lewy body diseases have been described, but their clinical relevance is not clear. Thirty PD cases from the United Kingdom Parkinson's Disease Society Tissue Bank were grouped as demented (PDD; n = 16) and nondemented (PD; n = 14) based on a review of clinical records. The extent of alpha-synuclein, tau, and amyloid beta peptide (Abeta) deposition in the caudate nucleus, putamen, and nucleus accumbens was assessed. All cases showed severe dopaminergic striatal terminal denervation based on tyrosine hydroxylase immunohistochemistry. Alpha-synuclein and tau deposition in the striatum were rare in both groups, but the Abeta burden was significantly greater in the striatum of PD cases with dementia than present in the nondemented PD group. Striatal Abeta deposition was type-independent of Alzheimer disease changes in the cortex and was minimal in nondemented PD cases. We conclude that Abeta deposition in the striatum strongly correlates with dementia in PD.
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PMID:Striatal beta-amyloid deposition in Parkinson disease with dementia. 1845 28

Whereas the prevalence and impact of vascular pathology in Alzheimer diease (AD) are well established, the role of vascular and Alzheimer pathologies in the progression of neurodegeneration and cognitive impairment in Parkinson disease (PD) is under discussion. A retrospective clinico-pathologic study of 100 patients with autopsy proven PD (including 44 cases with dementia/PDD) and 20 cases of dementia with Lewy bodies (DLB) confirmed essential clinical (duration of illness, Mini-Mental State Examination/MMSE, age at death) and morphologic differences between these groups; Lewy body Braak scores and Alzheimer pathologies (neuritic Braak stage, cortical Abeta plaque load, and generalized cerebral amyloid angiopathy or CAA) were significantly higher/more severe in DLB and PDD than in PD without dementia. Duration of illness showed no association to any of the examined pathologic parameters, while there was a moderate association between LB scores and neuritic Braak stages, the latter significantly increasing with age. Significant association between cerebrovascular lesions and neuritic Braak stage was seen in PDD but not in PD subjects without dementia. These data suggest an influence of Alzheimer-related lesions on the progression of the neurodegenerative process and, in particular, on cognitive decline in both PDD and DLB. On the other hand, both these factors in PD and DLB appear to be largely independent from coexistent vascular pathology, except in cases with severe cerebrovascular lesions or those related to neuritic AD pathology. Assessment of ApoE genotype in a small number of cases showed no significant differences in the severity of Abeta plaque load and CAA except for much lower intensities in non-demented epsilon3/3 patients. Despite increasing evidence suggesting synergistic reactions between alpha-synuclein (alphaSyn), tau and Abeta-peptides, the major protein markers of both AD and Lewy body diseases, and of both vascular pathology and AD, the molecular background and pathophysiological impact of these pathologies on the progression of neurodegeneration and development of cognitive decline in PD await further elucidation.
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PMID:Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. 1827 24

Parkinson's disease (PD) related dementia (PDD) develops in up to 60% of patients, but the pathophysiology is far from being elucidated. Abnormalities of resting state functional connectivity have been reported in Alzheimer's disease (AD). The present study was performed to determine whether PDD is likewise characterized by changes in resting state functional connectivity. MEG recordings were obtained in 13 demented and 13 non-demented PD patients. The synchronization likelihood (SL) was calculated within and between cortical areas in six frequency bands. Compared to non-demented PD, PDD was characterized by lower fronto-temporal SL in the alpha range, lower intertemporal SL in delta, theta and alpha1 bands as well as decreased centro-parietal gamma band synchronization. In addition, higher parieto-occipital synchronization in the alpha2 and beta bands was found in PDD. The observed changes in functional connectivity are reminiscent of changes in AD, and may reflect reduced cholinergic activity and/or loss of cortico-cortical anatomical connections in PDD.
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PMID:MEG resting state functional connectivity in Parkinson's disease related dementia. 1898 41

The rise in Infantile Autism, learning problems, cognitive decline with age, Alzheimer's, Parkinson's Diseases and the SIDS epidemic, has a common cause in the rising dietary deficit in Omega-3 brain-food. This paper suggests that aside from the wider concept of Autism Spectrum Disorders (ASD) and Pervasive Developmental Disorders (PDD), the rise in Infantile Autism (IA) in the last decade is the effect of deficient brain-food (Omega-3). The consequent delay of development prolongs the 2nd regressive event in infancy to pruning of the centre in the Medial Frontal Lobe System that connects Hippocampus and Cingulum. With a consequently defective Supplementary Motor Area (SMA), the Delayed Response Function is affected leading to persistent psychosis. Post-Pubertal Episodic Psychoses are associated with acute reduction of excitation, a risk of breakdown of circuitry, insufficient fill-in mechanisms, and silent spots. An acute psychosis occurs if the silent spots comprise of SMA. Only two brain areas have continuous neurogenesis, indicating their important functions: the Hippocampus and Olfactory Bulb that belongs to the Lateral Frontal Lobe System essential to survival. Concerned with necessity of action in response to the environment, it relies upon short-term memory and Acute Feedback Mechanisms influenced by emotion and motivation from the external world. In contrast, the Medial Frontal Lobe network is controlled by Feed-Forward Predictive Mechanisms related to storage of information. The Delayed Response Function is mastered at 7 months, when 2nd event occurs with pruning of axons and dendrites. An abolished or defective Delayed Response Function seriously incapacitates an individual: A defective "Social Brain" with an inability for conscious action and to communicate, predominates in IA. There is a near lack of speech, despite normal vision and hearing in the minority without marked adversity in pregnancy, at delivery or in infancy. I propose that the recent rise in IA despite no rise in adversity signifies a rising deficiency in brain-food. That this is so is suggested by a changing clinical picture: no Mental Retardation in an IA majority. Deficit in Olfaction is pathognomonic in schizophrenia since 30 yrs and distinguishes the Asperger Syndrome. If brain-food deficiency alone sufficiently prolongs pruning to cause absent activity in SMA in infancy, less mentally retarded IA from other causes might be observed. Deficit in brain-food was evident in the Sudden Infant Death Syndrome: birthweight averaged 200-300 g lower than sibs, Omega-3 levels in brainstem were lower than controls. Only 20 % SIDS died in first hypoxic episode, suggesting such episodes are more frequent than we imagined. Children with learning-behaviour problems have similarly depressed birthweight. A general deficiency in Omega-3 contributes to the lacking reduction in Schizophrenia, despite early puberty predominates. Olfactory Bulb is first affected in the Alzheimer's and Parkinson's Disease. Cognitive decline with age, Hippocampal dysfunctions rise markedly irrespective of disease, but the major mental illnesses and Infantile Autism in particular, benefit from "brain-food" that might also prevent a development of these disorders. To secure optimal brain function in the coming generations, there is a need to change the diet now from its emphasis on protein for body growth to food for the brain. This means there is a need to increase fish and sea food consumption.
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PMID:Infantile autism: a chronic psychosis since infancy due to synaptic pruning of the supplementary motor area. 1932 37

Dementia is a frequent non-motor feature of Parkinson's disease (PD). Elevated plasma homocysteine (Hcy) levels have been associated with both cognitive impairment and dementia. Increased Hcy levels have been observed in levodopa-treated patients with PD. The objective of our study was to evaluate the association between plasma Hcy levels and dementia in PD. We performed a multicenter cross-sectional study on patients with PD with (PDD) and without (PDnD) dementia and age- and sex-matched healthy controls. We compared Hcy levels in patients with PDD and PDnD and healthy controls, and we performed logistic regression analysis to search for an association between the presence of dementia and increased Hcy levels in PD. Patients with PD (121), PDD (42), and PDnD (79), and age- and sex-matched controls (154) were enrolled. Hcy levels were higher in patients with PD compared to controls (17.5 micromol/L +/- 10.2 vs. 11 +/- 4.1; P < 0.00001). Among patients with PD, Hcy levels were higher in the PDD group compared to the PDnD group (20.7 micromol/L +/- 12.1 vs. 15.8 +/- 8.5; P = 0.002). In a multivariate logistic regression model, higher Hcy levels [Odds ratios comparing the top (>18.9 micromol/L) with the bottom tertile (<12.4 micromol/L): 3.68; 95% CI: 1.14-11.83] were significantly associated with dementia. These data support the association between elevated Hcy levels and the presence of dementia in PD.
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PMID:Hyperhomocysteinemia in levodopa-treated patients with Parkinson's disease dementia. 1935 4

Cognitive impairment (CI) and dementia are frequent and debilitating features associated with Parkinson's disease (PD). Formal neuropsychological examination is required to ascertain the degree and pattern of CI over the course of the disease. The use of different tools may explain heterogeneous data obtained from studies to date. Normative data for extensively used scales [Mattis Dementia Rating Scale (MDRS), Mini-Mental State Examination (MMSE)] is incomplete in PD populations. According to sample characteristics, statistical analyses, and methodological quality, 33 studies using scales not specific to PD (MDRS, MMSE, Cambridge Cognitive Assessment, FAB) or PD-specific scales (Mini-Mental Parkinson, Scales for Outcomes of Parkinson's disease-Cognition, Parkinson's Disease-Cognitive Rating Scale, and Parkinson Neuropsychometric Dementia Assessment) were eligible for the critical analysis of their appropriateness to assess cognition in PD. Of the four scales specifically designed for PD, the SCOPA-COG and the PD-CRS have undergone extensive and rigorous validation processes. While the SCOPA-COG mainly assesses "frontal-subcortical" cognitive defects, the PD-CRS also assesses "instrumental-cortical" functions, allowing better characterization of the different patterns of CI that may be present in PD from the earliest stages. The MMP and PANDA scales were designed as brief screening tests for CI and have not yet been subjected to extensive clinimetric evaluations. Further research on PD-specific tools seems mandatory to help establish accurate cut-off scores for the diagnosis of mild PDD, detect cognitive profiles more prone to the future development of dementia, and allow comparisons between different descriptive or interventional studies.
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PMID:Cognitive impairment in Parkinson's disease: tools for diagnosis and assessment. 1935 27

The objective of this study is to investigate the safety and tolerability of memantine, a glutamatergic modulator, in patients suffering from dementia associated with Parkinson's disease (PDD), an increasingly common complication of PD. This was a 22-week trial of 25 participants with a DSM-IV diagnosis of PDD who were randomized to either placebo or 20 mg/day of memantine. Memantine was well tolerated by participants at 20 mg/day dosing. No participant was withdrawn due to memantine-related adverse events. Six weeks after drug withdrawal, a significantly greater proportion (P = 0.04) of memantine-treated participants deteriorated globally compared with those treated with placebo. These findings suggest that continued treatment with memantine may be needed to maintain global level of functioning over time. Based on the findings of this pilot study, memantine is safe and very well-tolerated in PDD.
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PMID:Randomized controlled trial of memantine in dementia associated with Parkinson's disease. 1937 Jul 37

Although dementia is increasingly recognized as a common feature in Parkinson's disease (PD), its pathological substrate remains unknown. We conducted cross-sectional and longitudinal brain perfusion SPECT analyses to explore changes during the course of developing dementia in PD. Fifty-five patients originally diagnosed with PD were imaged in the cross-sectional study. Twenty-one of these, nine without dementia and 12 with dementia (PDD), were included in the longitudinal study to observe perfusion changes during the course of their disease. Data were analyzed using three-dimensional stereotactic surface projection SPECT analysis. The UK Parkinson's Disease Society Brain Bank criteria were used to diagnose PD and the revised criteria for the clinical diagnosis of dementia with Lewy bodies for PDD. The cross-sectional study showed that patients with PDD had significantly reduced perfusion in the right posterior cingulate, the right precuneus and the left posterior cingulate area. In the longitudinal study, significantly reduced perfusion was observed in the left anterior frontal gyrus in PD without dementia, and in the right inferior parietal lobule in those that developed PDD. We suggest that a relationship exists between developing dementia in PDD and reduced perfusion in the posterior parietal area.
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PMID:Cross-sectional and longitudinal studies of three-dimensional stereotactic surface projection SPECT analysis in Parkinson's disease. 1944 Nov 30


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