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)

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

On mental status examinations, groups of equally impaired patients with subcortical (Huntington's disease, HD; Parkinson's disease, PD) or cortical (Alzheimer's disease, AD) dementias exhibit different patterns of neuropsychological deficits. Using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), classification accuracies of 90% or greater have been reported for individual patients with AD or HD. To test the generality of the RBANS classification algorithm, we studied patients with dementia (AD and PDD) and without dementia (PDND). Classification accuracies were AD: 87%, PDD: 78%, and PDND: 39%. Comparisons of performance on subtests of the RBANS showed that all groups performed more poorly on tests that require motor skill or rapid information processing and that memory performance by the PD groups was not improved by procedures that enhance encoding and facilitate retrieval. The RBANS is useful for discriminating patterns of cognitive impairment in PD and AD, but only if the diagnosis of dementia is established independent of the RBANS test results. Cognitive slowing is not specific to subcortical dementia and current concepts of memory dysfunction in PD may require re-examination.
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PMID:Analyzing the subcortical dementia syndrome of Parkinson's disease using the RBANS. 1459 46

Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.
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PMID:Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. 1474 92

Comparative investigation of motor and neuropsychological functions was conducted in 17 patients with clinically established diagnosis of dementia with Lewy bodies (DLB), 21 patients with Parkinson's disease (PD) without dementia and 26 patients with dementia (PDD). No significant differences were found in overall severity of parkinsonian features. However, comparing to PD, patients with DLB rarely had resting tremor, bilateral parkinsonism onset and good response to levadopa medication but more frequently exhibited gaze up palsy and myoclonus. Patients with PDD had more prominent akinesia, rigidity and axial disturbances, as compared to the PD patients without dementia, but there were no significant differences in these variables between patients with DLB and PDD. Comparing to PDD patients, those with DLB poorly performed on the tests measuring attention, verbal fluency and visual-spatial functions. Behavioral disturbances (especially apathy, aspontaneity, euphoria, obsessive-compulsive syndrome, dysinhibition, environment dependence) were severer in the patients with DLB and PDD, but no significant differences were found between these two groups. All the patients with DLB, 14 patients with PDD (53.8%) and 2 patients without dementia (7.4%) had psychotic disorders, which emerged later and were less pronounced in the patients with DLB compared to PDD patients. However, no significant differences were found in motor and neuropsychological impairment between DLB and PDD with psychotic disorders. The results may indicate a typological similarity of clinical manifestations of DLB and PDD that suggest nosologic proximity of these conditions included to synucleinopathies group.
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PMID:[Comparative study of Parkinson's disease and dementia with Lewy bodies]. 1487 Jun 86

Dopaminergic cell transplantation is a promising therapeutic approach for the treatment of Parkinson's disease, the potential of which is limited due to poor survival and low dopamine content within engrafted tissue. In this study, the ability of transforming growth factor-beta2 (TGF-beta2) to influence transplant survival was evaluated. Cell suspensions containing fetal rat ventral mesencephalon (VM) cells were incubated prior to surgery with vehicle (DPBS), varying concentrations of TGF-beta2 (5-1000 ng/ml), or a pan-specific antibody against TGF-beta (1D11, 100 ng/ml). VM cell suspensions (200,000 cells) were unilaterally implanted into the striatum of adult Sprague-Dawley rats (n = 5-11 animals/group). Following a 3-week survival period, small but viable VM grafts containing tyrosine hydroxylase-positive (TH+) neurons and fibers were present in all animals. Addition of TGF-beta2 resulted in a steep, bell-shaped dose-response curve with a significant effect on TH+/dopamine cell survival. At 50 ng/ml TGF-beta2, the number of surviving dopamine neurons was increased twofold compared with controls. Addition of TGF-beta2 or 1D11 did not significantly influence graft volume. Further studies, possibly in combination with other neurotrophic factors, need to be performed to obtain a greater understanding of the effects of TGF-beta on dopamine neurons and fetal VM cell engraftment.
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PMID:The effects of transforming growth factor-beta2 on dopaminergic graft survival. 1519 Nov 62

Dementia is a frequent complication of Parkinson's disease (PD) and usually occurs late in the protracted course of the illness. We have already reported numerous MHC class II-positive microglia in the hippocampus in PD patients, and that this phenomenon may be responsible for functional changes in the neurons and the cognitive decline in PD patients. In this study, we have investigated the distribution of activated microglia and the immunohistochemical and the mRNA expression of several cytokines and neurotrophic factors of the hippocampus in PD and dementia with Lewy bodies (DLB). The brains from five cases of PD and five cases of DLB that were clinically and neuropathologically diagnosed, and those from four normal controls (NC) were evaluated by immunohistochemistry using anti-HLA-DP, -DQ, -DR (CR3/43), anti-alpha-synuclein, anti-brain-derived neurotrophic factor (BDNF), and anti-glial fibrillary acidic protein antibodies. In addition, the mRNA expressions of cytokines (IL-1alpha, IL-1beta, TNF-alpha, IL-6, TGF-beta) and neurotrophic factors (BDNF, GDNF, NGF, NT-3) of these brains were evaluated by the reverse transcription-PCR method. MHC class II-positive microglia were distributed diffusely in the hippocampus of PD and DLB brains. Although the cytoplasm of pyramidal and granular cells of the hippocampus in NC brains was strongly stained by anti-BDNF antibodies, it was only weakly stained in PD and DLB brains. The mRNA expression of IL-6 was significantly increased in the hippocampus of PD and DLB brains, and that of BDNF was significantly decreased in the hippocampus of DLB brains. The increased number of activated microglia and the production of neurotrophic cytokines such as IL-6, together with the decreased expression of the neurotrophic factors of neurons in the hippocampus of PD and DLB brains, may be related to functional cellular changes associated with dementia.
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PMID:Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. 1561 28


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