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)

The distinctive clinical features of dementia in Parkinson's disease (PDD) and Parkinson's plus Alzheimer's disease (PD + AD) suggest different patterns of cerebral atrophy in these conditions. To determine the pathoanatomical substrates of dementia in PDD and PD + AD, morphometric analysis of 5 standardized coronal slices was used to identify volumetric changes in cerebral tissue. In PDD (n = 4) there were 9 to 23% reductions in cross-sectional area of cerebral cortex, a 38% loss of tissue in the globus pallidus + putamen, and an 18% reduction in area of the amygdala, whereas in PD + AD (n = 6) there was severe global atrophy of the cerebral cortex (27-29% reductions), moderate atrophy of white matter (10-19% reductions), and 40% reductions in areas of globus pallidus + putamen and the amygdala relative to neuropathologically intact controls (n = 14). Immunostaining with anti-glial fibrillary acidic protein disclosed significant gliosis of all four major subdivisions of neocortex in PD + AD and gray matter of the caudate, putamen, globus pallidus, and thalamus in both PDD and PD + AD relative to controls. The findings suggest that dementia in PDD is mainly subcortical in origin and due to neuronal degeneration in basal ganglia, the amygdala, and thalamus. In PD + AD the same pattern and degree of subcortical degeneration is evident, but there are clearly superimposed lesions involving cortical neurons and long projection fibers coursing through cerebral white matter that most likely account for the distinctive manifestations of dementia in this condition compared with PDD.
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PMID:Neuropathological distinction between Parkinson's dementia and Parkinson's plus Alzheimer's disease. 226 Aug 63

The clinical efficacy of dopamine (DA) replacement therapy for patients with Parkinson's disease (PD) depends on the preservation of postsynaptic DA receptors and their intracellular signalling mechanisms in the striatum long after degeneration of the nigrostriatal DA pathway. DA activates adenylyl cyclase (AC) and phospholipase C (PLC) via the D1 receptor, and inhibits through the D2 receptor, thereby regulating the production of intracellular second messengers, cyclic adenosine 3',5'-monophosphate (cAMP), 1,2-diacylglycerol (DAG) and Ca2+. Recent advances in molecular biology have made it possible to monitor the intracellular signal transduction cascade following receptor activation by various transmitters. The authors review the literature addressing this issue, summarized as follows: (1) striatal D1 and D2 receptor densities remain constant, at least in treated and non-demented patients; (2) DA-sensitive AC activity appears to be increased in the putamen of treated patients, although this remains to be confirmed; (3) levels of cAMP-dependent protein kinase (PKA) are normal in non-demented patients, consistent with unchanged levels of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of M(r) 32,000); (4) levels of Ca2+/phospholipid-dependent protein kinase (PKC) and of inositol 1,4,5-trisphosphate (InsP3) receptor also remain unchanged in non-demented patients; (5) the above three second messenger sites as well as densities of D1 and D2 receptors are decreased in the striatum of demented PD patients (PDD). We tentatively conclude that postreceptor signalling function is intact in the striatum of non-demented PD patients and that there is a clear difference between non-demented patients and PDD, i.e. striatal dopaminoceptive neurons are affected in PDD.
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PMID:Transmembrane signalling systems in the brain of patients with Parkinson's disease. 795 88

Alterations in protein kinase C (PKC) and myo-inositol 1,4,5-trisphosphate (IP3) receptors were studied in the autopsied human striata from 21 patients with Parkinson's disease (PD) (Yahr III, IV, and V), 8 patients with Huntington's disease (HD), and 23 age-matched and postmortem time-matched nonneurological controls. The concentrations of PKC and IP3 receptors were determined using [3H]4 beta-phorbol 12,13-dibutyrate (PDBu) and [3H]IP3 as respective ligands. Both the specific [3H]-PDBu and [3H]IP3 bindings were significantly reduced in the striata of Yahr V patients with dementia (PDD) and in that of HD patients, as compared to findings in the controls. These bindings were unchanged when all the PD patients without dementia, Yahr (III plus IV) patients, or Yahr V patients without dementia were compared with evidence from the controls. Immunoquantification of four PKC subspecies (alpha, beta I, beta II, and gamma) in the HD putamen revealed a selective reduction in the beta II-PKC immunoreactions. These results are supported by immunohistochemical findings in the rat brain that beta II-PKC is expressed in the striatal gabaergic efferent pathway, while the alpha-PKC is present in the nigrostriatal dopaminergic neurons. The neurochemical pathophysiology of PD differs between patients with and without dementia.
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PMID:Second messenger systems in brains of patients with Parkinson's or Huntington's disease. 809 76

Cognitive impairment and dementia are common in the later stages of Parkinson's disease (PD). Neuropathological examination of demented PD (PDD) patients often reveals changes that are typical of Alzheimer's disease (AD). In AD, there is a massive reactive gliosis and increased expression of the small heat shock proteins (hsp) hsp27 and alpha B-crystallin. Since these proteins are characteristic for reactive astrocytes in AD, we investigated their expression in the brains of PDD patients. The results were compared with those obtained in the brains of non-demented PD patients. We found (1) no detectable expression of hsp in PD without dementia, and low expression in PD with mild dementia; (2) reactive gliosis and increased expression of hsp in the cortex of PDD brains; (3) a strong association between hsp immunoreactivity and the severity of the AD-specific changes, especially with the number of tangles in the hippocampus; (4) a distinct immunoreaction of alpha B-crystallin in microglia in the substantia nigra and in the hippocampus in PDD. These results indicate that astrocytes react to the disease conditions in AD and in PDD in a similar way, namely by the increased expression of small heat shock proteins, and present additional evidence for the thesis that the pathology of the dementia in PD is related to that in AD.
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PMID:Dementia, gliosis and expression of the small heat shock proteins hsp27 and alpha B-crystallin in Parkinson's disease. 1043 47

We measured total glutathione concentrations in the cerebrospinal fluid (CSF) of non-demented Parkinson's disease patients (PD; n=71), demented PD patients (PDD; n=13), multiple system atrophy patients (MSA; n=10), Alzheimer's disease patients (AD; n=17) and age-matched controls (n=21). No statistically significant differences in the mean total CSF glutathione concentrations were found between groups and dopaminomimetic treatment was not found to have any effect on total CSF glutathione levels. Our main conclusion is that total glutathione is not useful as a CSF marker for assumed oxidative stress in patients with PD, MSA or AD.
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PMID:Normal cerebrospinal fluid glutathione concentrations in Parkinson's disease, Alzheimer's disease and multiple system atrophy. 1052 92

Previous research suggests that lexical and semantic verbal fluency are differentially sensitive to the effects of cortical and subcortical dementias, but little is known about action fluency performance in dementias. The present study compared lexical, semantic, and action fluency in groups of patients with Parkinson's disease (PD) with and without dementia and an elderly control group. Findings revealed an interaction between fluency type and subject group. Although the demented PD (PDD) group performed significantly more poorly than their non-demented counterparts and normal controls on all three fluency tasks, a disproportionate disparity in scores was noted on the action fluency task. The findings suggest that action fluency may be particularly sensitive to PD-associated dementia and may be an early indicator of the conversion from PD to PDD. As reported elsewhere, PD without dementia was not associated with significant impairment on any of the fluency tasks.
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PMID:Lexical, semantic, and action verbal fluency in Parkinson's disease with and without dementia. 1055 Aug 4

Patients suffering from Parkinson's disease (PD), often develop dementia (PDD). Their brain histology reveals Alzheimer's disease (AD) like changes and decreased cholin-acetyl transferase (ChAT) activity, in addition to typical PD changes. This cholinergic deficiency has been related to the degree of mental decline. As centrally acting cholinesterase inhibitors (ChEIs) provide cognitive and non-cognitive improvement for AD patients, the same therapeutic effect was hypothesized for PDD patients as well. The goal of this study was to assess the effect of ChEIs on both the cognitive and motor state of PDD patients. An open study was conducted. Eleven consecutive PDD patients (M/F 6/5 mean age 75 y) were found eligible for inclusion. They were treated for 26 weeks with tacrine (7 patients) and donepezil (4 patients) as add-on to their regular anti PD drugs. Cognitive assessment was performed at baseline and endpoint by Mini-Mental-State-Examination (MMSE) and Alzheimer's-Disease-Assessment-Scale (ADAS-cog). Global Deterioration Scale (GDS) was performed to evaluate active daily living (ADL). Motor evaluation was performed using Short Parkinson Evaluation Scale (SPES) at baseline and end-point. Statistical analysis used Student's paired t-test, ANOVA with repeated measures and Pearson correlation coefficient. ChEIs treated PDD patients showed improvement in their cognitive state. Mean ADAS-cog improved significantly by 3.2 points (p < 0.012). Mean MMSE and GDS improved non-significantly by 1.2 and 0.2 points respectively. There was no change in motor function as evident by mean SPES scores, 16.5 at baseline and endpoint. Five individuals actually demonstrated motor improvement under ChEIs. We conclude that ChEIs have a beneficial effect on the cognitive state of PDD patients without aggravating motor function.
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PMID:The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson's disease and dementia. 1176 30

We investigated the relative differences in dopaminergic function through the whole brain in patients with Parkinson's disease without dementia (PD) and with dementia (PDD) using 6-[18F]fluoro-L-dopa (18F-dopa) PET and a voxel-by-voxel analysis. The 10 PD and 10 PDD patients were equivalently disabled, having mean scores of 3.2 +/- 0.6 and 3.2 +/- 0.7, respectively, on the Hoehn and Yahr rating scale. 18F-dopa influx constant (Ki) images of those patients and 15 normal age-matched subjects were transformed into standard stereotactic space. The significant differences between the groups (expressed in mean regional Ki values) were localized with statistical parametric mapping (SPM) on a voxel-by-voxel basis. Compared with the normal group, SPM localized declines of the 18F-dopa Ki bilaterally in the putamen, the right caudate nucleus and the left ventral midbrain for the PD group (P < 0.01, corrected). Compared with the normal group, the PDD group showed reduced 18F-dopa Ki bilaterally in the striatum, midbrain and anterior cingulate area (P < 0.01, corrected). A relative difference in 18F-dopa uptake between PD and PDD was the bilateral decline in the anterior cingulate area and ventral striatum and in the right caudate nucleus in the PDD group (P < 0.001, corrected). Accordingly, we conclude that dementia in PD is associated with impaired mesolimbic and caudate dopaminergic function.
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PMID:Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[18F]fluoro-L-dopa PET study. 1202 24

Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.
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PMID:Parkinson's disease is associated with hippocampal atrophy. 1281 57

Risk factors predicting an increased risk of dementia in Parkinson's disease (PD) are not fully established. The dementia associated with PD (PDD) closely resembles dementia with Lewy bodies (DLB). Based upon a high frequency of non-dopaminergic mediated clinical features in DLB, we predicted that a motor subtype comprising postural instability and balance problems would be more common in PDD. We examined extrapyramidal, cognitive, and affective features in 38 PD, 43 PDD, and 26 DLB patients in a cross-sectional study design. Motor subtype was subdivided into postural-instability gait difficulty (PIGD) or tremor (TD) dominant. The PIGD-subtype was more common in PDD (88% of cases) and DLB (69% of cases) groups compared with the PD group (38% of cases), in which TD and PIGD sub-types were more equally represented (P < 0.001). Although the mean depression scores overall were modest, PDD patients scored significantly higher than PD, but not DLB patients (Cornell; P = 0.006, and Geriatric Depression scale, GDS-15; P = 0.001), while within the PD group, those patients with a PIGD subtype had greater depression scores than the TD subtype (GDS-15; P < 0.05). We conclude that non-dopaminergic motor features are frequent in PDD. Neurodegeneration within the cholinergic system is likely to mediate many of these motor problems, as well as playing a significant role in determining the neuropsychiatric symptomatology of both PDD and DLB.
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PMID:Extrapyramidal features in Parkinson's disease with and without dementia and dementia with Lewy bodies: A cross-sectional comparative study. 1288 77


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