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)

Recent epidemiological and clinico-pathological data suggest overlaps between Alzheimer's disease (AD) and cerebrovascular lesions (CVL) that may show some synergistic effects, but the results of studies of the relationship between AD and stroke have been controversial. The objective of this study was to compare the frequency of cerebral infarcts, hemorrhages and minor cerebrovascular lesions in autopsy-confirmed AD and age-matched control brains. Using current routine and immunohistochemical methods 173 consecutive cases of autopsy-confirmed AD and 130 age-matched controls were compared. The total incidence of vascular pathology (56.5%) in AD was significantly less than in a previously reported smaller AD autopsy cohort (82.3%) (P<0.01), and was higher than in controls (42.4%). The incidence of severe CVL (old and recent infarcts, hemorrhages) in our cohort was slightly higher (12.7%) than in controls (8.5%), that of minor to moderate CVL (lacunes, cerebral amyloid angiopathy with or without minor vascular lesions) was more frequent in AD (43.8%) than in controls (33.9%), but the results were not statistically significant (P<0.03). The brain weight and severity of cognitive decline did not correspond to the degree of vascular pathology, but higher neuritic Braak scores and reduced brain weight contributed to the production of cognitive impairment. Like previous findings in Parkinson's disease, our data do not indicate a protective effect from stroke or a significantly greater susceptibility to death from stroke in AD in the population studied, but further prospective clinico-pathological studies are necessary.
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PMID:Incidence of cerebrovascular lesions in Alzheimer's disease: a postmortem study. 1247 55

Supra-pontine lesions resulting from neurological disorders such as vascular disease, Parkinson's disease, or Alzheimer type senile dementia lead to an increase in bladder activity. This is due in part to the removal at the cortical inhibitory control of the micturition center in the brain stem - i.e. the pontine micturition center (PMC) - and in part to facilitation of excitatory control. These inhibitory or excitatory controls consist of several neurotransmitter systems, including glutamate, dopamine, gamma-aminobutyric acid (GABA), and acetylcholine. Bladder overactivity caused by cerebral infarction is mediated by upregulation of N-methyl-D-aspartate (NMDA) glutamatergic and D2 dopaminergic excitatory mechanisms, and by downregulation of NMDA glutamatergic and Ml muscarinic inhibitory mechanisms in the brain. Bladder overactivity associated with Parkinson's disease is reportedly induced by a loss of input to the D1 dopaminergic receptor. Furthermore, bladder overactivity caused by Alzheimer type dementia is thought to be mediated by downregulation of M1 muscarinic inhibitory mechanisms. Development of bladder overactivity following cerebral infarction is mediated by activation of the NMDA receptor and accompanied by an increase in c-fos, zif268 and COX-2 mRNA expression in the dorsal pontine tegmentum.
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PMID:Overactive bladder--experimental aspects. 1247 19

We report a sporadic case of unusual cerebral amyloid angiopathy (CAA) with prominent capillary involvement. A 67-year-old doctor developed gait disturbance, resting tremor and rigidity. He was diagnosed to have Parkinson's disease, for which the treatment with levodopa was effective. Four years later he began to exhibit progressive cognitive decline and behavioral abnormalities consisting of hallucination and agitation. Subsequently, his condition steadily worsened and became bedridden with severe dementia, and he died eight years after the disease onset. During the clinical course, there had been no episode of stroke. Postmortem examinations revealed the typical pathology of Parkinson's disease with frequent cortical Lewy bodies in the amygdala. The most striking pathological feature of this patient was widespread CAA where prominent beta-amyloid (A beta) deposition was observed in the capillaries of the neocortex, most pronouncedly in the occipital lobe, as well as leptomeningeal and cerebral medium-sized and small vessels. Further, perivascular plaques were found in half of the amyloid-laden capillaries. Tau-positive dystrophic neurites were only sparsely detectable within a few perivascular plaques. Despite the severe A beta pathology, there was no microaneurysmal dilatation, fibrinoid necrosis or vascular occlusion. There was only one small ischemic lesion in the brain. The cerebral white matter was unremarkable. Senile plaques of neuritic type and neurofibrillary tangles were mostly limited to the hippocampal regions and, to a lesser degree, in the amygdaloid nucleus, which did not meet the neuropathological criteria of Alzheimer's disease. On the gene analyses, his apolipoprotein E (ApoE) genotyping was verified to be heterozygous epsilon 3/epsilon 4, and no mutation was seen in exons 16 and 17 of the amyloid precursor protein gene. Severe A beta capillary angiopathy as seen in our patient is exceptional in sporadic CAA. Further, A beta angiopathy of this patient was notable in the absence of an associated cerebrovascular disease despite prominent A beta deposition in the vessel walls. Regarding the development of his severe dementia, the limbic pathology of Lewy body disease might be one of the potential causes, but A beta angiopathy appears more likely because of its severity. We speculate that widespread A beta deposition disregulates the blood-brain barrier of the capillaries leading to a disturbance of the microcirculation throughout the cerebral cortex without obvious ischemic disintegration of the neuropil. We should take into consideration that A beta angiopathy can present as progressive dementia without cerebrovascular disease.
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PMID:[Sporadic cerebral amyloid angiopathy presenting with dementia and prominent capillary beta-amyloid deposition: a case report]. 1260 81

Data on the relationship between Parkinson's disease (PD) and stroke have been conflicting, some studies showing a reduced risk of stroke during life, and others indicating an increased risk of stroke-related death. Consecutive cases (n=617) of autopsy-proven idiopathic PD (Lewy body disease of the brain stem type) and age-matched controls (n=535) were compared using current routine and immunohistochemical methods. The total frequency of cerebrovascular lesions (lacunes, amyloid angiopathy, white matter lesions, old and recent ischemic infarcts and hemorrhages) in PD (44.0%) was higher than in controls (32.8%), while acute, often fatal ischemic or hemorrhagic strokes were less frequent in parkinsonian patients (1.8% vs 2.6%). Like previous postmortem findings in a smaller cohort, these findings neither indicate a protective effect against stroke nor a greater susceptibility to death from stroke in the populations studied. Cognitive impairment in PD appears to be largely independent from coexistent vascular pathology except in cases with severe cerebrovascular lesions.
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PMID:Prevalence of cerebrovascular lesions in Parkinson's disease. A postmortem study. 1267 40

The frequency of vascular lesions in dementia with Lewy bodies (DLB) has been suggested to be less common than for Parkinson disease (PD), but exact data on the relationship between DLB and stroke are not available. 387 consecutive cases of autopsy-proven Lewy body disease - 291 cases of idiopathic PD (Lewy body disease of brainstem type) and 96 cases of DLB - and 390 age-matched controls were compared using current routine stains and immunohistological methods. The frequency of cerebrovascular lesions of various intensity (lacunes, amyloid angiopathy, old ischemic infarcts and hemorrhages) was lower in DLB than in both PD and controls (34.4% vs. 36.7% and 33.3%) (p > 0.03). While acute ischemic strokes and hemorrhages were rarely present in both PD and controls (4.1 vs. 3.3%), no such lesions were observed in DLB. At variance to previous findings in autopsy-proven PD and Alzheimer disease (AD), these data suggest a protective effect against stroke and no greater susceptibility to death from stroke in the DLB population studied, but the reasons remain unclear. On the other hand, like in PD and AD, cognitive impairment in DLB appears to be independent from coexisting vascular pathology and is mainly related to neuritic Alzheimer pathology.
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PMID:Prevalence of vascular lesions in dementia with Lewy bodies. A postmortem study. 1281 37

The diagnosis of Parkinson's disease (PD) is clinical and is based on the identification of a combination of the cardinal motor signs of bradykinesia plus at least one of the following: rigidity, tremor or postural instability. There are many causes of parkinsonism such as drug induced parkinsonism, subcortical vascular disease, and multisystem atrophy. PD is a well characterised syndrome which represents only a part of the various causes of parkinsonism. A good response to dopaminergics is an important diagnostic criteria for PD. Pharmacotherapy for PD relies primarily on levodopa and dopamine agonists. Deep brain stimulation is increasingly used in the management of patients with severe dopa fluctuations and dyskinesias. Cholinesterase inhibitors are introduced for dementia in parkinsonism. Neuroprotective compounds, nerve growth factors such as GDNF and the implantation of dopaminergic cells are studied in clinical trials.
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PMID:[Diagnosis and treatment of Parkinson's syndrome. What is important for the general practitioner?]. 1457 97

The clinical severity of late onset Parkinson's disease (PD) varies from patient to patient and it is further complicated by the increasing prevalence of accompanying disorders in the elderly. We set out to study the impact of ischemic heart disease, minor stroke, hypertension and diabetes mellitus in a group of late onset PD patients (age >or=70 years). Consecutive late onset PD patients seen in the Department of Neurology, Medical School of Patras, Greece were included in this study. We used very strict criteria to eliminate the possibility of including patients with vascular parkinsonism. Comparisons were made between groups of patients suffering with idiopathic Parkinson's disease (IPD) and the above-mentioned diseases. One hundred and sixty-seven consecutive late onset PD patients were included in this study. The most common accompanying disorders in our group were hypertension in 31 (18%) of the patients and minor stroke in 20 (12%). The Hoen and Yahr score in late onset IPD patients who suffered from minor stroke, ischemic heart disease or diabetes mellitus was significantly higher when compared with patients without the above disorders. The results clearly suggest that the presence of vascular disease on an IPD patient may aggravate PD severity. In clinical grounds, these findings can be proved significant since early and aggressive prevention of vascular disease and treatment of vascular risk may contribute in controlling symptom severity in PD.
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PMID:The effect of vascular disease on late onset Parkinson's disease. 1698 45

Vascular parkinsonism has not been well defined and the clinical correlation of vascular parkinsonism is still not clear. The aim of the study was to estimate prevalence of occurrence of vascular parkinsonism, analysis of risk factors leading to its development and to identify clinical features that suggest a vascular origin. 214 patients with Parkinson's disease were examined. Their ages ranged from 37 to 88 years (median 66.4 years). Evidence of vascular parkinsonism was assessed using a vascular rating scale previously described by Winikates and Jankovic. Statistical analysis was performed with Mann-Whitney U test, chi 2 Pearson test, chi 2 Yates test, Spearman rank correlation and Student's t test. Out of 214 patients 8 were proved to have developed Parkinson's disease due to vascular disease, what gave 3.74%. Out of risk factors for stroke 5 patients had hypertension, 3 had diabetes mellitus, 2 suffered from heart disease, 2 had infarctus myocardii, 1 had hyperlipidemia, 1 had atrial fibrillation. Additionally, those patients had neuroimaging (CT or MRI) evidence of vascular disease in one or more vascular territories. Patients with vascular parkinsonism were older, had shorter duration of disease, were more likely to present rigidity rather than tremor. Dementia and incontinence were more common in vascular group than in Parkinson's disease group. Patients with vascular parkinsonism were also significantly more likely to have corticospinal findings. Proving that Parkinson's disease had vascular etiology is extremely difficult. The test results are inconclusive.
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PMID:[Clinical correlation of vascular parkinsonism]. 1509 42

Hyperhomocysteinemia is as a risk factor for increased vascular disease in l-dopa-treated Parkinson disease (PD) patients. This effect of l-dopa is associated with the metabolism of l-dopa by methylation. This study aimed to assess the effect of pergolide on plasma homocysteine levels. Plasma homocysteine levels were compared between PD patients treated with pergolide as monotherapy, with l-dopa as monotherapy, or with an l-dopa and pergolide combination and compared with controls. Plasma homocysteine levels were significantly higher in the l-dopa monotherapy group, and there were no significant differences for the pergolide treatment groups. Pergolide can be beneficial for increased plasma homocysteine levels.
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PMID:Plasma homocysteine levels in pergolide-treated Parkinson disease patients. 1531 1

Deposition of amyloid-beta, the fibrillogenic product of the cell surface protein AbetaPP (amyloid-beta protein precursor), occurs in the cerebral cortex of patients with Dementia with Lewy bodies (DLB). Amyloid deposition, basically in the form of senile plaques, occurs not only in the common form (DLBc), which is defined by changes consistent with diffuse Lewy body disease accompanied by Alzheimer's disease (AD), but also in the pure form (DLBp), in which neurofibrillary tangles are absent. The present study analyses the expression of AbetaPP mRNA isoforms with (AbetaPP751 and AbetaPP770) and without (AbetaPP695) the Kunitz-type serine protease inhibitor (KPI) domain, in the cerebral cortex in DLBc (n=4), DLBp (n=4), Parkinson's disease (PD, n=5), AD (n=3 stages I-IIA, and n=4 stage VC of Braak and Braak), amyloid angiopathy (AA, n=2) and progressive supranuclear palsy (PSP, n=4) compared with age-matched controls (n=6). For this purpose, TaqMan RT-PCR assay was used on frozen post-mortem samples of the frontal cortex (area 8) obtained with short post-mortem delays (8.29+/-4.57 h) and strict RNA preservation (A260/280 of 1.78+/-0.15). A 3.66-fold, 6.67-fold, 4.28-fold and 5.24-fold increases, in the (AbetaPP751+AbetaPP770)/AbetaPP695 mRNA ratio were found in DLBc, DLBp, AD stage VC and AA, respectively, when compared with controls. No modifications in the ratio were found in PD, AD stage I-IIA and PSP. These findings suggest that alternative splicing of the AbetaPP mRNA may play a role in betaA4 amyloidogenesis in DLBp, DLBc, AD stage VC and Amyloid angiopathy.
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PMID:Amyloid-beta deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in AbetaPP mRNA isoforms containing the Kunitz protease inhibitor. 1567 Jun 42


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