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Query: UMLS:C0752347 (Dementia with Lewy bodies)
 1,653 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify those patients most likely to benefit from a cerebral biopsy to diagnose dementia, we reviewed a series of 14 unselected biopsies performed during a 9-year period (1980 through 1989) at Duke University Medical Center, Durham, NC. Pathognomonic features allowed a definitive diagnosis in seven specimens. Nondiagnostic abnormalities but not diagnostic neuropathologic changes were seen in five additional specimens, and two specimens were normal. Creutzfeldt-Jakob disease was the most frequent diagnosis. One patient each was diagnosed as having Alzheimer's disease, diffuse Lewy body disease, adult-onset Niemann-Pick disease, and anaplastic astrocytoma. We conclude that a substantial proportion of patients presenting clinically with atypical dementia are likely to receive a definitive diagnosis from a cerebral biopsy. However, in those with coexisting hemiparesis, chorea, athetosis, or lower motor neuron signs, cerebral biopsies are less likely to be diagnostic.
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PMID:Evaluation of cerebral biopsies for the diagnosis of dementia. 172 59

Amyloid P (AP) component is present in all types of systemic amyloid deposits. Recently, it has been shown to be also present in cerebral amyloid lesions of Alzheimer's disease (AD). In this study, we used immunocytochemical methods to extend these findings at the electron microscope level and characterize the spectrum of AP immunoreactivity in neurofibrillary pathology (NFP) of AD and other neurodegenerative disorders including Down's syndrome (DS), Creutzfeldt-Jakob, Parkinson's, Pick's and diffuse Lewy body diseases and progressive supranuclear palsy. In AD and DS, AP immunoreaction product was evident in all the classical amyloid lesions and NFP in a large sample of all cortical areas examined. The distribution and relative intensity of immunostaining was similar to that of thioflavin S staining in serial sections. In many cases, however, plaques and vessels stained by anti-AP serum were not apparent with thioflavin S. Serial sections immunostained with antiserum to amyloid A, C-reactive protein or to other proteins involved in systemic amyloidoses and the acute phase response showed no evidence of staining in any of the cerebral lesions. Electron microscopy confirmed that AP immunoreactivity was associated with the abnormal filaments characteristic of NFP as well as amyloid fibrils found in plaques and vessels showing congophilic amyloid angiopathy. Plaques of Creutzfeldt-Jakob disease, Pick bodies of Pick's disease, tangles and Lewy bodies in Parkinson's disease and a subpopulation of Lewy bodies in the diffuse Lewy body disease coexistent with AD were also stained. With the exception of vessels in two of the five cases, AP was not detected in age-matched controls. Our observations indicate AP to be a consistent feature of cerebral NFP and amyloid deposits.
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PMID:Widespread serum amyloid P immunoreactivity in cortical amyloid deposits and the neurofibrillary pathology of Alzheimer's disease and other degenerative disorders. 189 Oct 63

The neuropathological heterogeneity of Alzheimer's disease (AD) is increasingly recognized. Diffuse Lewy body disease, for example, most frequently occurs in cases fulfilling histopathological criteria for AD, and these patients usually present with dementia rather than parkinsonism. We report five cases of concomitant AD and diffuse Lewy body disease with still another coexistent neuropathological feature: localized and stereotyped spongiform change in the neuropil. This spongiform change was most striking in the superior and inferior temporal, entorhinal, and insular cortex and the amygdala and was virtually indistinguishable from that seen in Creutzfeldt-Jakob disease. Electron microscopic study on one case revealed membrane-containing vacuoles in close association with neuritic plaques and plaired helical filament-filled processes. Immunocytochemistry using antibodies to prion proteins (PrPsc or PrP27-30) failed to label plaque or vascular amyloid in the five cases. Four primates inoculated with brain tissue from one case have not evidenced neurological disease in the 3 years since the transmission experiment. We conclude that these cases represent a neuropathological subset of AD with relatively widespread Lewy bodies and a localized spongiform change, predominantly involving the medial temporal region. Despite the light and electron microscopic commonality with Creutzfeldt-Jakob disease, there is no clear evidence that these cases represent a form of transmissible spongiform encephalopathy.
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PMID:A neuropathological subset of Alzheimer's disease with concomitant Lewy body disease and spongiform change. 254 59

Community pathologists are often called on to perform autopsies to confirm clinical diagnoses of Alzheimer's disease, by far the most common cause of dementia. Diagnostic criteria have been provided by the Consortium to Establish a Registry for Alzheimer's Disease. Beyond pure and simple Alzheimer's disease, a significant proportion of dementia brains will feature Alzheimer's disease mixed with Lewy bodies, historically associated with idiopathic Parkinson's disease, or combined with various manifestations of cerebrovascular disease. Less commonly, the pathologist will encounter Lewy body disease alone, pure cerebrovascular disease, Pick's disease, progressive supranuclear palsy, Creutzfeldt-Jakob disease, or dementia lacking distinctive histopathology. This article is intended to reacquaint pathologists with these disorders and to provide a practical step-by-step approach to making the diagnosis of these mixed and non-Alzheimer's dementias.
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PMID:Making the diagnosis of mixed and non-Alzheimer's dementias. 748 2

Movement disorders presenting with parkinsonism may share histopathological features with Creutzfeldt-Jakob disease, a spongiform encephalopathy caused by the accumulation of pathological prion protein in brain. To investigate a possible aetiological link between these conditions and Creutzfeldt-Jakob disease, histoblot immunostaining for pathological prion protein was carried out in 90 cases including idiopathic Parkinson's disease, multiple system atrophy, diffuse Lewy body disease, Steele-Richardson-Olszewski syndrome, corticobasal degeneration, and Pick's disease. Pathological prion protein was identified in four controls with Creutzfeldt-Jakob disease but not in any of the other diseases examined. The findings suggest that an aetiological role for prions in these movement disorders is unlikely. Histoblotting provides a useful method for screening large areas of tissue for the presence of pathological prion protein and may be helpful in the differential diagnosis of difficult cases.
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PMID:Absence of disease related prion protein in neurodegenerative disorders presenting with Parkinson's syndrome. 793 89

A 30-year-old woman suffered from a progressive extrapyramidal syndrome, myoclonic jerks, spasticity, and organic brain syndrome; she was clinically suspected to suffer from Creutzfeldt-Jakob disease and died after 4 years of illness. At autopsy, widespread dystrophic axons and Lewy bodies (LBs) were found in her brain. Neuronal loss and diffuse reactive astrogliosis involved the gray matter including the cerebral cortex. Dystrophic axons occurred throughout the nervous system except for the cerebellar cortex and peripheral nerves. LBs involved the cerebral cortex as well as subcortical regions including amygdala and claustrum, brainstem including substantia nigra and locus coeruleus, and spinal cord. LBs were distributed extensively enough to be compatible with diffuse Lewy body disease (DLBD). Ubiquitin immunostaining labeled both dystrophic axons and LBs. The combination of neuroaxonal dystrophy and DLBD may result from cytoskeletal pathology which affects both neuronal cell bodies and axons with subsequent deficient proteolysis and ubiquitination.
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PMID:Neuroaxonal dystrophy combined with diffuse Lewy body disease in a young adult. 839 56

The presence of apolipoprotein E-epsilon4 (APOE-epsilon4) allele has been implicated as a risk factor for Alzheimer's disease (AD). We examined the frequencies of APOE-epsilon4 alleles in age-matched controls and subgroups of 190 AD subjects exhibited cerebral amyloid angiopathy (CAA) and other frequently associated lesions. CAA was evident in 96% of the AD subjects, which were divided into two groups, one bearing mild or no apparent CAA and the other with moderate to severe CAA. APOE-epsilon4 allele frequency (48%) in the latter advanced CAA group was six times higher than in those who exhibited mild CAA. In the advanced CAA subjects, the occurrence of an epsilon4 allele was increased by a factor of 17 (95% confidence interval, 7.56 to 38.9). This was despite the fact that neocortical amyloid-beta plaque densities in the two groups were similar and that all of the AD subjects had met the accepted neuropathological criteria. We also observed that the degree of CAA severity was greatest in the group of subjects with the epsilon4/epsilon4 genotype. The association between CAA and APOE-epsilon4 was further implicated in two non-AD subjects among neurological controls with severe CAA. These two subjects, both homozygous for the APOE-epsilon4 allele, were primarily diagnosed as having Creutzfeldt-Jakob disease and Pick's disease in the absence of significant neocortical amyloid deposition. Allele frequency comparisons between neurological control subjects with CAA and those without likewise accorded a strong relationship between the APOE-epsilon4 allele and the presence of CAA. More remarkably, the epsilon4 allele frequency was highly associated with AD subjects exhibiting lobar or intracerebral hemorrhage, all of whom had advanced CAA. We observed that 36% of the AD subjects had concomitant cerebrovascular pathology resulting from single infarcts, multiple microinfarcts, ischemic white matter lesions, or petechial hemorrhages. Although the difference in APOE genotype distribution between subjects with and without cerebrovascular lesions did not reach statistical significance, we did note that the frequency of the epsilon4 allele was significantly higher in subjects with such pathology as compared with those without. However, we found no evidence to suggest that the acquisition of an APOE-epsilon4 allele or one of the alleles, epsilon2 or epsilon3, was a factor in the occurrence of atherosclerosis localized in the basal surface arteries. Analyses of our sample also confirm that there was a lower frequency of the APOE-epsilon2 allele in AD subjects and that the frequency of the epsilon4 allele in AD subjects with concomitant diffuse Lewy body disease was intermediate between controls and AD subjects. Our results suggest that the APOE-epsilon4 allele is a significant factor in the development of CAA in AD and reveal the possibility that APOE is an independent factor in CAA and other vascular abnormalities associated with AD.
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PMID:Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. 866 92

Before the advent of ubiquitin immunochemistry and immunogold electron microscopy, there was no known intracellular molecular commonality between neurodegenerative diseases. The application of antibodies which primarily detect ubiquitin protein conjugates has shown that all of the human and animal idiopathic and transmissible chronic neurodegenerative diseases, (including Alzheimer's disease (AD), Lewy body disease (LBD), amyotrophic lateral sclerosis (ALS), Creutzfeldt-Jakob disease (CJD) and scrapie) are related by some form of intraneuronal inclusion which contains ubiquitin protein conjugates. In addition, disorders such as Alzheimer's disease, CJD and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins which may be associated with cytoskeletal reorganisation. Although our knowledge about these diseases is increasing, they remain largely untreatable. Recently, attention has focused on the mechanisms of production of different types of amyloid and the likely involvement within cells of the endosome-lysosome system, organelles which are immuno-positive for ubiquitin protein conjugates. These organelles may be 'bioreactor' sites for the unfolding and partial degradation of membrane proteins to generate the amyloid materials or their precursors which subsequently become expelled from the cell, or are released from dead cells, and accumulate as pathological entities. Such common features of the disease processes give new direction to therapeutic intervention.
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PMID:Endosome-lysosomes, ubiquitin and neurodegeneration. 886 Oct 20

The accuracy of the clinical diagnosis of corticobasal degeneration (CBD) is unknown. To determine its diagnostic accuracy, we presented 105 cases with known neuropathologic diagnoses, including CBD (n = 10), progressive supranuclear palsy (PSP, n = 24), Parkinson's disease (n = 15), diffuse Lewy body disease (n = 14), multiple system atrophy (n = 16), postencephalitic parkinsonism (n = 7), Pick's disease (n = 7), Creutzfeldt-Jakob disease (n = 4), Alzheimer's disease (n = 4), vascular parkinsonism (n = 3), and Whipple's disease (n = 1), as clinical vignettes to six neurologists unaware of the autopsy findings. Reliability was measured with the kappa statistics. The neurologists' clinical diagnoses were compared with clinicopathologic diagnoses for sensitivity, specificity, and positive predictive values at first and last clinic visits. The group reliability for the diagnosis of CBD significantly improved from moderate for the first visit (mean = 34 months after onset) to substantial for the last (68 months after onset). For the first visit, mean sensitivity for CBD was low (35%), but specificity was near-perfect (99.6%). For the last visit, mean sensitivity minimally increased (48.3%), and specificity remained stable. False-negative misdiagnoses mainly occurred with PSP. False-positive diagnoses were rare. The extremely low sensitivity of the clinical diagnosis of CBD suggests that this disorder is markedly underdiagnosed. Although the validity of the clinical diagnosis might have been improved if neurologists could have examined these patients, more important is that this disorder was misdiagnosed by the primary neurologists. In our data set, the best predictors for the diagnosis of CBD included limb dystonia, ideomotor apraxia, myoclonus, and asymmetric akinetic-rigid syndrome with late onset of gait or balance disturbances.
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PMID:Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. 900 6

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


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