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)

In the absence of pathognomonic clinical features, the clinical diagnosis of Alzheimer's disease (AD) remains one of exclusion of other dementias. We investigated the clinical diagnoses among 394 neuropathologically confirmed AD cases in a dementia brain bank. Most patients were correctly diagnosed as AD (348 or 88%). Among the misdiagnosed patients, AD was mistaken for a primary depressive disorder in 14, multi-infarct dementia in 13, Parkinson's disease in nine, and alcoholic dementia in four. The number of misdiagnosed AD patients did not differ between physician specialties but was greater among AD patients with agitation, depression, paranoia, or delusions. This retrospective study suggests that the diagnostic sensitivity for AD is high among a cross-section of practicing physicians and that an important factor in mistaking AD for another illness is unfamiliarity with the potential psychiatric symptoms of AD.
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PMID:Neuropathologically confirmed Alzheimer's disease: clinical diagnoses in 394 cases. 205 48

Paquid is an epidemiological study designed to gather and follow up a cohort of 4,000 elderly subjects (65 years and older) living at home in order to study normal and pathological brain aging. These subjects were randomly chosen in the general population of 75 communities of South-Western France. We present the results of the data collected from 2,792 subjects on the prevalence and the correlates of clinically diagnosed dementia. The DSM III criteria for dementia were met by 101 subjects (3.62 p. 100). These cases were reviewed by a neurologist to confirm the diagnosis and to determine the cause of dementia using the NINCDS-ADRDA criteria. Forty-three subjects were classified as probable Alzheimer's disease; 8 as possible Alzheimer's disease; 5 as vascular dementia; 5 as Parkinson's disease with dementia; 2 as alcoholic dementia; 2 as "dementified psychosis"; and 1 unclassified. Fifteen patients refused to be examined by the neurologist, 18 were false-positives, and 2 died before the neurologists visit. Using the NINCDS-ADRDA criteria, the prevalence of dementia was as low as 1.6 p. 100. The prevalence of probable Alzheimer's disease decreased dramatically as educational level increased, lung 5.4 p. 100 for subjects with no education, 1.7 p. 100 for subjects with grade school level, 0.4 p. 100 for subjects with high school level and 0.4 p. 100 for subjects with university degrees. The relationship between dementia and educational level is still controversial in the literature. In this study the sample was large and randomly selected; all the demented cases fulfilled the NINCDS-ADRDA criteria. This suggests that educational level is indeed an important correlate of dementia in the French elderly community.
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PMID:[The Paquid research program on the epidemiology of dementia. Methods and initial results]. 206 70

We present a review on recent neuroimaging techniques, like x-ray computed tomography (XCT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission tomography (SPECT) in dementia and related diseases. Significant new findings have been obtained using techniques reflecting proton density, regional brain perfusion and brain metabolism. In dementia of the Alzheimer type, for example, temporoparietal and sometimes also frontal reductions in cerebral blood flow and metabolism are characteristic. The infarctions found in multi-infarct dementia are especially well visualized on T2-weighted MRI images. Pick's disease is characterized by brain atrophy and decrease of radiotracer activity in the frontal lobes. In huntington's chorea the metabolic rate on PET scan in the area of the caudate nuclei may be reduced even before signs and symptoms become apparent. Furthermore, neuroimaging provides us with fairly typical finding in Creutzfeld-Jakob's disease, alcoholic dementia, Wilson's disease, hydrocephalus, Parkinson's disease, progressive supranuclear ophthalmoplegia, Fahr's disease, and the olivopontocerebellar ataxias. Neuroimaging techniques, however, have always to be interpreted in conjunction with clinical findings, thus disclosing their full range of information.
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PMID:[Diagnostic differentiation of dementia diseases by modern imaging procedures]. 227 95

Total muscarinic receptor levels, the levels of the subtypes exhibiting high and low affinity for pirenzepine, and the high- and low-affinity agonist states of the receptor were investigated in hippocampal tissue obtained at autopsy from mentally normal individuals and the following pathological groups: Alzheimer's disease, Parkinson's disease, Down's syndrome, alcoholic dementia, Huntington's chorea, and motor-neurone disease. A moderate decrease in the density of both high-affinity pirenzepine and high-affinity agonist subtypes was found in Alzheimer's disease, whereas a trend towards an increase in the overall muscarinic receptor density was apparent in the parkinsonian patients without dementia, mainly due to an increase in the low-affinity agonist state; the differences between the Alzheimer's disease and nondemented parkinsonian cases were highly significant. As previously reported, the levels of both choline acetyltransferase and acetylcholinesterase were markedly reduced in both Alzheimer's disease and Parkinson's disease--with a greater loss of both enzymes in the demented subgroup of parkinsonian patients. Activities of the cholinergic enzymes were also extensively reduced in Down's syndrome, accompanied by a loss of high-affinity pirenzepine binding. There were no significant receptor or enzyme alterations in the other groups studied. These observations suggest that in the human brain, extensive degeneration of cholinergic axons to the hippocampus, as indicated by a loss of cholinergic enzymes, is not necessarily accompanied by extensive muscarinic receptor abnormalities (as might be expected if a major subpopulation were presynaptic). Moreover, the opposite changes in muscarinic binding in Parkinson's and Alzheimer's diseases may be related to the greater severity of dementia in the latter disease.
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PMID:Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. 333 58

Cholinergic receptors (muscarinic subtypes M1 and M2, and putative nicotinic binding) have been examined in the hippocampus obtained at autopsy from a variety of patients with cognitive disorders (Alzheimer's, Parkinson's, and Huntington's diseases, Down's Syndrome and alcoholic dementia) and compared with neurologically normal controls and cases of Motor Neuron disease. In all of the disorders associated with a pre-synaptic cortical cholinergic deficit reflected by an extensive loss of choline acetyltransferase (Alzheimer's disease, Parkinson's disease and Down's Syndrome) there was a substantial reduction in the binding of (3H) nicotine to the nicotinic receptor. By contrast reductions in both muscarinic subtypes (M1 and M2) were apparent to only a moderate extent in Alzheimer's disease, whereas in Parkinson's disease binding was significantly increased (apparently not in relation to anti-cholinergic drug treatment) in the non-demented but not demented cases. A further abnormality detected in Alzheimer's disease but not the other disorders investigated was a decrease in an endogenous inhibitor of nicotinic binding, the identity of which is as yet unknown but which may be a candidate for a possible endogenous modulator of the nicotinic receptor. These observations suggest that in Alzheimer's disease not only muscarinic but also nicotinic receptor function should be considered in relation both to future therapeutic strategies and, in the search for a clinical marker which might be of diagnostic value, to potential probes of the cortical cholinergic system.
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PMID:Cholinergic receptors in cognitive disorders. 379 Oct 66

Apolipoprotein E (ApoE) genotyping was conducted in sporadic Alzheimer's disease (AD, n = 91) as well as in other dementing disorders including Parkinson's disease (PD, n = 73), autopsy-confirmed diffuse Lewy body disease (DLBD, n = 16), progressive supranuclear palsy (n = 13), vascular dementia (n = 55), alcoholic dementia (n =25) and normal control subjects (n = 77). ApoE epsilon 4 allele frequency was significantly higher in AD (33.5%, p < 0.001), DLBD (40.6%, p < 0.001) and demented PD (29.4%, p < 0.05) compared to that in normal controls (11.7%). The association of the ApoE epsilon 4 allele with AD was more pronounced in early-onset AD (46.4%) than in late-onset AD (27.8%). 46% of the AD individuals developed AD without association to ApoE epsilon 4, and epsilon 4 homozygotes were found not only in AD, but also in many of other dementing disorders. These results suggest that ApoE genotyping cannot provide certainty about the presence of absence of AD, and that it should be used as an adjunct to other diagnostic tests for AD. On the other hand, cerebrospinal fluid (CSF) tau levels were significantly elevated (p < 0.0001) in AD (78.0 +/- 44.2 pg/ml) compared to those in normal controls (10.6 +/- 8.6 pg/ml). The specificity and the sensitivity of distinguishing AD from normal controls was 95.0 and 91.2%, respectively. Elevated CSF-tau levels were also detected in some patients with acute neurological diseases including meningoencephalitis, Creutzfeld-Jacob disease, normal pressure hydrocephalus and vitamin B12 deficiency encephalopathy. Increased CSF-tau levels in AD were found regardless of the age at onset, clinical stage, ApoE genotype, alpha 1-antichymotrypsin genotype, and presenilin-1 genotype. The CSF-tau levels continued to be abnormal during the progression of AD. These results suggest that CSF-tau serves as an unequivocal and reliable biological marker to aid in the clinical diagnosis of AD.
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PMID:Apolipoprotein E genotyping and cerebrospinal fluid tau protein: implications for the clinical diagnosis of Alzheimer's disease. 918 33

Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post-translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities.
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PMID:Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress. 2688 65