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At least 19 recordsLinked to original sources
PubMed1987

Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia).

Four patients with severe dementia and a parkinsonian syndrome are described. Dysphasia, dyscalculia, dyspraxia, visual and verbal memory disturbance and psychosis, usually of depressive type, occurred early in the course of the illness. Pathologically they were characterized by the presence of numerous Lewy bodies throughout both the cerebral cortex and brainstem. Three cases also had severe neurofibrillary tangle change or senile plaques in the neocortex, compatible with Alzheimer's disease, but the cortical tangle distribution did not always match that of the Lewy bodies. This disorder may form part of the spectrum of pathology in Parkinson's disease, where it may be one possible cause of dementia.

Adult↗
PubMed2002

Familial Lewy body diseases.

Lewy body disease includes clinically and pathologically defined disorders in which Lewy bodies occur in the nervous system. In recent years, the molecular features of these disorders have been emerging. Several genetic loci have been identified in association with familial Lewy body disease; however, the genetic risks underlying most cases of familial Lewy body disease remain to be discovered. The fact that Lewy bodies stain strongly with antibodies to asynuclein and that mutations in the alpha-synuclein gene lead to syndromes in which parkinsonism and dementia occur gives us important clues regarding the biologic processes leading to disease. Pursuit of additional mendelian causes of familial Lewy body disease and study of the factors contributing to the complex phenotypes associated with Lewy body disorders will elucidate underlying disease pathways and, thus, possible targets for therapeutic intervention.

Aged↗
PubMed1992

[From Parkinson's disease to Lewy body disease].

Lewy bodies are intraneuronal inclusions initially found in the pigmented brainstem nuclei of patients with Parkinson's disease. Their aspect varies according to their neuronal or cerebral situation. They have been a long time the hallmark of Parkinson's disease, but in recent years it has emerged that a small group of rare disorders or rare variants of common degenerative diseases are also sometimes associated with Lewy bodies in the nervous system. Pathological studies have also individualized a new disorder characterized by the presence of numerous Lewy bodies throughout the cerebral cortex and the brainstem: Lewy body disease. The clinical syndrome associates dementia, parkinsonian features, dysautonomia and motor neuron disease. The dementia is cortical in type and psychiatric symptoms such as agitation, hallucinations or delusions are frequent. The pathological features are nerve cell loss, diffuse Lewy bodies, and sometimes senile plaques. The origin of this disorder remains unclear, but it could be a primitive abnormality of neuronal cytoskeleton.

Alzheimer Disease↗
PubMed1996

Lewy bodies are located preferentially in limbic areas in diffuse Lewy body disease.

Lewy bodies (LBs)are found throughout the brain stem, limbic and neocortical areas in Parkinson's disease. Lewy bodies are also associated in these areas with dementia and the substrate of 'dementia with Lewy bodies' is thought to include Lewy body pathology in limbic and neocortical areas with or without Alzheimer-type changes. In order to determine whether dementia with Lewy bodies is characterised primarily by cortical or limbic LB pathology, we have measured the density of Lewy bodies, neuritic plaques and neurofibrillary tangles in 12 neocortical, limbic and brain stem sites in 10 patients who were pathologically diagnosed with diffuse Lewy body disease (DLBD) (64.7 +/- 2.7 years). The mean LB density in limbic areas (3.00 +/- 0.61/mm2) was significantly greater than that of neocortical areas (1.13 +/- 0.22/mm2, P < 0.001). The greatest density of LBs was found in the amygdala (4.1 +/- 0.7/mm2) and the lowest in the occipital cortex (0.3 +/- 0.1/mm2). In limbic areas, LB formation positively correlated with neuritic plaque formation (r = 0.51, P < 0.01) but not with neurofibrillary tangle densities. These data indicate that dementia with Lewy bodies is characterised primarily by limbic, and secondly by neocortical, LB pathology. It remains to be determined why limbic areas are selectively vulnerable to LB pathology in dementia with Lewy bodies.

Aged↗
PubMed1997

[Diffuse Lewy body disease].

Lewy body disease (LBD) is a progressive neurological disorder with parkinsonism, having many Lewy bodies (LBs) and degenerative changes. LBD is classified into the three types according to the distribution of LBs: "brain-stem type", "transitional type" and "diffuse type". The brain-stem type is identical to classical Parkinson's disease (PD). The diffuse type is nominated as "diffuse Lewy body disease" (DLBD). DLBD is a neuropathological entity, characterized by abundant LBs not only in the basal ganglia and brain-stem but in the cerebral cortex, combined with senile changes. Juvenile onset DLBD is called "pure form" of DLBD because of no or few senile changes. The LBs are present in the amygdala, nucleus basalis of Meynert, hypothalamic nuclei, substantia nigra, nucleus paranigralis, locus caeruleus, dorsal vagal nucleus and reticular nuclei. The cerebral LBs are numerous in the parahippocampal gyrus, cingular gyrus, and insular, frontal and temporal cortices. The LBs show immunoreactivity to ubiquitin and the ubiquitin-immunoreactive neurites in the CA2-3 region appear to be specific for DLBD. The clinical features of DLBD in the senium are progressive dementia, psychotic state, parkinsonism and autonomic signs. In general, progressive dementia is an initial symptom, followed by parkinsonism in the later stage. Some show progressive autonomic failure. A few present respiratory failure or vocal cord palsy resulting in sudden death in DLBD. DLBD is characterized neurochemically by severe affection of multiple neurotransmitters networks. In DLBD an impairment of the innominato-cortical cholinergic and mesocortical dopaminergic system, differentiating from Alzheimer's disease and PD, may play an important role in developing disease process.

Humans↗
PubMed1996

Lewy body disease.

Lewy bodies have historically been considered a histopathologic hallmark of idiopathic Parkinson's disease. Recently, it has become clear that Lewy bodies play a role in neurodegenerative processes other than idiopathic Parkinson's disease, including diffuse Lewy body disease and diffuse Lewy bodies with concomitant Alzheimer's disease changes. It is likely that these processes represent a spectrum of neurodegenerative change in which Lewy bodies play a pivotal role. Although much is known and has been written regarding the histopathology and pathophysiology of Lewy body diseases, specific criteria for their diagnosis remain problematic. Within the spectrum of Lewy body disease, overlap in clinical presentation and histopathologic findings has caused some to dismiss attempts at subcategorizing Lewy body disease as artificial. We present, in brief, current information and theories concerning the pathology and pathogenesis of Lewy body disease.

Alzheimer Disease↗
PubMed1996

Purification and characterization of Lewy bodies from the brains of patients with diffuse Lewy body disease.

Lewy bodies (LBs) are the pathological hallmarks of degenerating neurons in the brains of patients with Parkinson's disease and diffuse Lewy body disease. We developed a novel purification procedure for LBs using sucrose density separation followed by fluorescence-activated particle sorting, and we raised > 15 monoclonal antibodies to LBs purified from diffuse Lewy body disease brains. The monoclonal antibody that stained the largest number of LBs most intensely did not recognize ubiquitin in free or monoubiquitinated forms nor the ubiquitin conjugating enzymes, but it did react with polyubiquitin chains as well as with high molecular weight polyubiquitinated LB-derived proteins. Thus, these results suggest that LBs contain polyubiquitin chains. Although polyubiquitination of LB proteins may trigger ubiquitin-proteasome proteolytic pathways, the incomplete activation of these pathways could play a mechanistic role in the formation of LBs in neurodegenerative diseases.

Aged↗
PubMed2004

Multiplication of the alpha-synuclein gene is not a common disease mechanism in Lewy body disease.

Lewy body disease (LBD) refers to a heterogeneous group of disorders presenting with parkinsonism and Lewy body (LB) formation. Although the relationship between dementing syndromes with LBs, Parkinson's disease, and Alzheimer's disease is unclear, the former constitute a common form of degenerative dementia and may account for up to 20% of cases in the elderly. We recently demonstrated triplication of the alpha-synuclein gene as the cause of disease in the Spellman-Muenter kindred. Neuropathological examination of affected members of the kindred demonstrated extensive LB pathology consistent with diffuse LBD. We examined a large collection of pathologically confirmed LBD cases and found no evidence for multiplication of the alpha-synuclein gene, suggesting that this mechanism is not a common cause of LBD.

Aged↗
PubMed1997

Alzheimer's disease, Lewy body disease and aging: a comparative study of the perforant pathway.

The relationship between Alzheimer's disease (AD) and Lewy body disease (LBD) is poorly understood. In AD there is severe loss of neurons comprising the perforant pathway. To assess perforant pathway integrity in pure LBD we compared neuronal counts in layer II of the entorhinal cortex (ERC) in 11 cases of pure LBD that did not meet CERAD pathologic criteria for AD with ERC neuronal counts from seven AD cases with a similar disease duration and six cognitively normal individuals. We counted cell bodies/island in layer II of the ERC using formalin-fixed, paraffin-embedded, tau/cresyl violet-stained sections at the level of the rostral-most body of the hippocampus. There was marked variability in neuronal counts among cases in the LBD group; LBD data overlapped with data from both normal and AD groups. Overall, perforant pathway perikaryal counts in LBD differed significantly from those in AD, but not from those in aged normals (mean perikarya/island = 30.09 +/- 8.95, 7.57 +/- 6.08, and 38.83 +/- 8.98, respectively; F = 26.131, P < 0.001). The percent of remaining neurons bearing neurofibrillary tangles in LBD also overlapped with AD and control groups (16.17 = 13.85%, 87.86 +/- 11.81%, and 24.36 +/- 13.30% of remaining neurons, respectively, F = 65.62, P < 0.001). We conclude that although perforant pathway neuronal loss may occur in LBD, it is more often milder and more variable than that seen in AD.

Adult↗
PubMed1997

Neurofibrillary tangles in the dentate granule cells of patients with Alzheimer's disease, Lewy body disease and progressive supranuclear palsy.

Recent studies have shown that the dentate granular cells of the hippocampus are affected in patients with Alzheimer's disease (AD). To gain a better understanding of the cytoskeletal alterations in these cells, we carried out immunocytochemical and immunoelectron microscopic analysis of the dentate gyrus of patients with primary degenerative dementias, using a monoclonal antibody against paired helical filaments (TG3). This antibody labeled a large number of spherical inclusions in the dentate granule cells of patients with AD and its Lewy body variant (LBV). These inclusions consisted of straight tubular structures (about 18-25 nm in diameter), similar to those found in progressive supranuclear palsy (PSP). These inclusions, although in a smaller number, were also found in demented patients with PSP, but not in those with diffuse Lewy body disease or age-matched controls. These findings indicate that the neurofibrillary alterations in the dentate granule cells of patients with AD, LBV and PSP share cytoskeletal similarities.

Alzheimer Disease↗
PubMedDate not supplied

Neuropathological diagnoses in elderly patients in Oslo: Alzheimer's disease, Lewy body disease, vascular lesions.

Neuropathological changes in elderly residents of Oslo, Norway were characterised with respect to the cerebral substrates of dementia. Ninety-two brains were examined, representing 41% of all deaths occurring in 10 nursing homes during a 9-month period. The autopsy cohort showed a similar mean age (85 years) and sex ratio (73% female) and proportion of demented patients (75%) compared to all the patients resident in these homes who died during the same period. Clinical data was compiled retrospectively. Diagnosis was made using the CERAD protocol, and criteria for the diagnosis of Lewy body dementia. Lewy body formation was present in 20% and cerebral infarction in 21% of patients. In the demented group (69 patients) 90% fulfilled CERAD criteria for definite or probable Alzheimer's disease. Eight demented cases had absent neocortical neurofibrillary tangles and 6 other cases showed Lewy body dementia (9% of demented patients). A further 8 of these demented cases had brain stem Lewy bodies with only minimal cortical involvement. Thirteen cases (19% of the sample) had cerebral infarcts but these were considered to be clinically significant in only 4 (6%). In the non-demented patients (23) 4 patients had brain stem Lewy bodies and 6 had cerebral infarcts. Despite inclusion criteria biased towards the collection of Alzheimer's disease and normal patients, both Lewy body dementia (7%) and cerebral infarcts contributing to dementia (6%) were frequent.

Aged↗
PubMed1994

Alzheimer's disease and Lewy body disease: a comparative clinicopathological study.

The exact nature of the relationship between Lewy body disease and Alzheimer's disease (AD) is unknown. To investigate this, we compared cases of pure Lewy body disease, mixed Lewy body disease with AD, and pure AD to see what pathological features were shared and how they differed. We counted neurons, Lewy bodies, diffuse and neuritic senile plaques, neurofibrillary tangles, and neuropil threads in the frontal and medial temporal cortex and hippocampus from 5 autopsied cases of Lewy body disease (without AD histopathology), 7 with combined Lewy body disease and AD, 6 with AD, and 5 age-matched normal control subjects. Average neuronal counts in the cases with Lewy body disease were indistinguishable from those of control subjects, but higher than those for AD and combined Lewy body disease and AD. Diffuse plaque densities were similar in all disease forms. Neuritic senile plaques, neurofibrillary tangles, and neuropil threads were numerous in AD and combined Lewy body disease and AD, but sparse or absent in Lewy body disease and controls. Pure Lewy body disease and AD appear to be distinct clinicopathological entities except for the common feature of diffuse plaques in both disorders.

Aged↗
PubMed2001

Diffuse Lewy Body Disease.

Diffuse Lewy body disease (DLB) is a neurodegenerative disorder characterized by dementia, fluctuations in mental status, hallucinations, and parkinsonism. Diffuse Lewy body disease is the second most common cause of dementia, following Alzheimer's disease. The treatment of DLB includes cholinergic therapy for cognitive impairment, atypical neuroleptics to alleviate hallucinations, and levodopa/carbidopa to improve parkinsonism. The recognition and diagnosis of DLB has critical treatment implications. Centrally acting cholinesterase inhibitors, such as rivastigmine, donepezil, and galantamine partially reverse decreased cortical cholinergic activity and may improve cognition and neuropsychiatric symptoms in DLB. Rivastigmine has been demonstrated to improve cognition and neuropsychiatric symptoms in patients with DLB without worsening parkinsonian features. Due to the potential adverse events associated with neuroleptics in this population, treatment with cholinesterase inhibitors is currently considered first-line therapy in the treatment of hallucinations and mental status fluctuations in DLB. Exquisite sensitivity to neuroleptic medications is a hallmark of DLB and life-threatening complications have been reported. Caution should be exercised when implementing antipsychotic therapy for the treatment of behavioral disturbances of DLB. When required, atypical neuroleptics with the least extrapyramdial side effects, such as quetiapine, should be used. The parkinsonian features of DLB may respond to dopaminergic therapy with levodopa. If parkinsonian symptoms result in clinical disability, a trial of levodopa is warranted. Unfortunately, dopaminergic medications may worsen hallucinations. Because dopamine agonists have a greater tendency to induce hallucinations and somnolence, levodopa is the treatment of choice for parkinsonism in DLB. Rapid eye movement (REM) sleep behavior disorder (RBD) is now recognized as a feature of DLB. Awareness of the presence of this symptom in patients with DLB is important and treatment with low dose clonazepam may help. Cholinergic aumentation may also improve these symptoms in patients with DLB.

Journal Article↗
PubMed1995

[Diffuse Lewy body disease].

Diffuse Lewy body disease (DLBD), which we have proposed since 1976, has received great attention among both researchers and clinicians. Recently, it was reported by some English and American research groups that DLBD is the second most frequent dementing illness in the elderly, following Alzheimer-type dementia (ATD). Our recent research of 79 autopsied dementia cases in a hospital disclosed that DLBD (15.4%) was the second most common degenerative dementia, following ATD (43.6%). In 1980 we proposed Lewy body disease, and classified it into three types: brain stem type, transitional type, and diffuse type. Diffuse type of LBD is now called DLBD. In 1990 we divided DLBD into two forms: common form and pure form. The common form of DLBD has more or less Alzheimer pathology, and pure form has none. Very recently, we proposed the cerebral type of LBD, in which numerous Lewy bodies are found in the cerebral cortex and amygdala, but no PD pathology is present in the brain stem. Therefore, LBD is now classified as follows: [table: see text]

Brain↗
PubMed2002

Glial involvement in diffuse Lewy body disease.

Diffuse Lewy body disease (DLBD) is characterized by the presence of Lewy bodies (LB) in the neurons and neurites of cortical, subcortical, and brain stem structures. Recently, alpha-synuclein (alphaS) has been found to be a central constituent of LB. In DLBD, abnormal accumulation of alphaS has been reported in both neurons and glia, but studies on glial lesions in DLBD have been limited. We examined in detail the constituents and distribution of glial lesions in eight patients with DLBD and report the pathogenesis of the glial lesions. alphaS-positive neuronal cytoplasmic inclusions (NI), neuropil threads (NT), and coiled bodies (CB) showed similar immunostaining profiles. Without pretreatment, NI, NT, and CB were detected by all antibodies against alphaS. The immunostaining profile of star-like astrocytes (SLA) was quite different from those of NI, NT, and CB. A few SLA were stained by an antibody against the non-Abeta component portion of alphaS without pretreatment, but formic acid pretreatment dramatically enhanced SLA immunoreactivity. SLA and CB were found in all eight brains with DLBD. SLA were scarce in the brain stem, but there were hundreds of SLA per visual field at x100 magnification in the temporal cortex of most cases, while CB were found diffusely in both the cerebral cortex and brain stem, similar to NI. This suggests that the pathogenesis of SLA is different from those of NI and CB.

Aged↗
PubMed2000

[Diffuse Lewy body disease].

Diffuse Lewy body disease is the second cause of dementia after Alzheimer's disease. It is characterized by a progressive dementia, often difficult to differentiate from Alzheimer's disease, but fluctuations of cognitive deficits, frequent hallucinations, delirium, hypersensitivity to neuroleptics, unexplained falls, atypical receiving "black-outs" and parkinsonian features are characteristics features evocative of the diagnosis. The response to anticholinesterase medication is often much better than in Alzheimer's disease.

Biopsy↗
PubMed2000

Diffuse Lewy body disease.

Diffuse Lewy body disease (DLBD) has been studied from various viewpoints and, although clinical diagnostic criteria for DLBD have been proposed, diagnosis remains difficult. DLBD has been reported to be the second most common form of dementia in the aged, following Alzheimer-type dementia. It has, however, been clinically under-diagnosed. Therefore, the search for diagnostic markers for DLBD must continue. Very recently, 'dementia with Lewy bodies' (DLB) was proposed as a generic term for various forms of dementia with Lewy bodies, including DLBD and similar disorders. Cortical Lewy bodies are the most important pathologic marker for diagnosis of DLBD. At present, however, the mechanism responsible for cortical Lewy body formation has yet to be disclosed.

Brain↗