Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.
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PMID:Clinical neurochemistry: developments in dementia research based on brain bank material. 986 26

Psychosis has been recognized as a common feature in neurodegenerative disease for many years. Hallucinations, delusions, and other psychotic phenomena occur in a wide range of degenerative disorders including Alzheimer disease, Huntington disease, Parkinson's disease, diffuse Lewy body disease, "Parkinson plus" syndromes, Pikc's disease, and other frontotemporal degenerations, amyotrophic lateral sclerosis, and prion associated diseases. It is also interesting that neurodegenerative disease-type dementia may be a feature in some psychotic illnesses such as schizophrenia. Clinical evaluation of psychosis in the setting of dementia presents a significant challenge for clinicians and researchers. Amnesia, language or speech impairments, and behavioral problems amy distort and obscure the presentation of symptoms. However, recognition and understanding of the psychotic manifestations may lead to the institution of more effective therapeutic or preventive options that can serve to delay long term care placement and improve patient and caregiver quality of life. In addition, a more comprehensive understanding of the pathophysiology, neuroanatomical substrates, and distinctive pathological features underlying the development of psychotic symptoms in neurodegenerative diseases may provide important insights into psychotic processes in general.
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PMID:Psychosis in Neurodegenerative Disease. 1032 Apr 31

We report a rare familial case of dementia with Lewy bodies (DLB). The patient was a man who died at the age of 51. His parents were first cousins. Among three siblings, two were diagnosed as probable cases of DLB, and one was a possible case, according to the clinical diagnostic criteria of the consortium on DLB. Following the patient's autopsy, he was found to have had DLB without neurofibrillary tangles or senile plaques (pure form of diffuse Lewy body disease). His other siblings have been followed for more than ten years. Although these patients with familial DLB displayed clinical variability, all three siblings showed progressive dementia of early onset and progressive language disorder with paraphasia and difficulty in finding words. Psychotic features were also seen in the three siblings. The patient's sister showed compulsive behavior, and the other two siblings showed symptoms of parkinsonism. Neuropathologically, in addition to the usual neuropathology of DLB, the autopsy findings showed numerous small spheroids in the stratum pyramidale from the subiculum to CA1 of the hippocampus. Significant neuronal loss in CA2-3 of the hippocampus was detected. Axonal flow disturbance may be involved in the hippocampal formations of this incidence of familial DLB.
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PMID:Familial dementia with Lewy bodies (DLB). 1050 32

Dementia with Lewy bodies (DLB) has been associated with important behavioural disturbances, such as psychotic symptoms. Unfortunately, neuroleptic sensitivity in these patients limits effective pharmacological management of these symptoms. Seven patients, five male and two female (mean age 75.3+/-4.7 years, range 68-81), diagnosed with DLB were treated with the acetylcholinesterase inhibitor donepezil (5-10 mg once daily) to determine its effect on treating behavioural disorders. Although the intended length of treatment was a minimum of 8 weeks, only three patients completed 8 weeks of therapy, one patient completed 6 weeks, two patients completed 4 weeks and one patient was discontinued after 5 days. The primary outcome (behavioural disturbances) was measured prospectively by the Neuropsychiatric Inventory (NPI), while other outcomes included cognition (Mini-Mental State Examination (MMSE)) and Clinical Global Impression. Three of the seven subjects showed marked improvement in behaviour, with NPI scores dropping significantly over time. Donepezil therapy was discontinued prematurely in three of the cases due to insufficient response and/or adverse events. Overall, five of the seven patients were rated at least minimally improved in behavioural symptoms. Our experience with donepezil in this group of patients shows promise. Given the limited experience with this agent in treating behavioural disorders associated with DLB, further studies are warranted.
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PMID:Donepezil for behavioural disorders associated with Lewy bodies: a case series. 1076 34

The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson's disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the alpha-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight alpha-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with alpha-synuclein immunostaining, including pleomorphic Lewy bodies, synuclein-positive glial inclusions and widespread, severe neuritic dystrophy. We also discuss the relationship of this familial disorder to a Lewy body disease clinical spectrum, ranging from Parkinson's disease to dementia with psychosis.
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PMID:Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p. 1086

Alzheimer's disease (AD) has become recognised as a major cause of morbidity and mortality in the ageing population worldwide. Over 20 million people worldwide are affected by AD, which ensures that the disease imposes a major economic burden. Alzheimer's disease is a progressive neurodegenerative disorder with characteristic clinical and neuropathological features. Neurofibrillary tangles, neuritic plaques and amyloid angiopathy occur in varying severity in brains of patient's with Alzheimer's disease. Biological markers of AD allowing an early definitive premorbid diagnoses are currently not available. Memory loss for recent events is invariable and often the earliest prominent symptom. Language disorders, difficulties with complex tasks, depression, psychotic symptoms and behavioral changes are other common manifestations of AD. Diagnosis involves the early detection of cognitive decline and ruling out other causes of dementia like vascular dementia, Lewy body dementia, fronto-temporal degeneration or reversible causes like hypothyroidism. Acetylcholinesterase inhibitors have shown to be effective in mild to moderate AD in improving the cognitive function of patients in clinical trials. Caregiver intervention programs have considerable potential to improve both the caregiver and patient quality of life.
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PMID:Diagnosis and management of Alzheimer's disease--an update. 1107 82

Dementia with Lewy bodies is a relatively common cause of dementia. Much has been learned about this disorder, yet much remains to be elucidated, especially in regard to early clinical diagnosis. To clarify the future research agenda in this area, the authors critically appraise the literature on cognitive and behavioral changes in DLB and provide a brief overview of the history of DLB, the main pathological changes, and the findings related to extrapyramidal symptoms and treatment issues. Twenty-one studies on cognition and 47 on behavioral changes in DLB are reviewed. Impairments of working memory and visuospatial functions, visual hallucinations, and depression (or symptoms of depression such as apathy and anxiety) have been identified as early indicators of DLB. However, longitudinal and cross-sectional data are lacking, particularly for different aspects of working memory, visual perception, and non-psychotic behavioral symptoms.
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PMID:A review of the cognitive and behavioral symptoms in dementia with Lewy bodies. 1108 60

There is a now a substantial body of evidence that suggests the new antipsychotic agent, risperidone, may be safe and effective for treating psychotic, affective or behavioural symptoms associated with various disorders other than schizophrenia, schizophreniform disorder or schizo-affective disorder. These conditions include bipolar disorder, obsessive-compulsive disorder, Tourette's syndrome, dementia, Lewy body disease, mental retardation, Parkinson's disease, idiopathic segmental dystonia and organic catatonia. Although much of the data is anecdotal or in the form of open studies, there is now emerging a small number of well controlled investigations supporting efficacy for mania, dementia, behavioural disturbance in mental retardation and conduct disorder. Conventional antipsychotics have long been used, either in a primary capacity or as an adjunct to treat these disorders; however, they have limited benefit, pose significant risks of extrapyramidal side-effects, and may cause the potentially life-threatening neuroleptic malignant syndrome. In contrast, risperidone at the recommended low doses may be efficacious and pose reduced risk of motor side-effects. This article reviews the evidence that risperidone may be an effective new treatment for disorders other than schizophrenia.
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PMID:Does risperidone have a place in the treatment of nonschizophrenic patients? 1119 55

Dementia with Lewy bodies (DLB) accounts for 15 to 20% of late-onset dementias. The overlap of cognitive symptoms, neuropsychiatric features, parkinsonism and severe sensitivity to antipsychotic drugs raise a number of key management issues. The neurochemical profile of DLB provides a good theoretical rationale for the potential value of cholinesterase inhibitor therapy, which is supported by clinical evidence from a number of case series and one placebo-controlled double-blind trial. It appears that cholinesterase inhibitor treatment is well tolerated and improves fluctuating confusion, cognition and psychotic symptoms; however, the evidence can still only be considered preliminary and a further double-blind study is imperative. Given the high prevalence of severe sensitivity to antipsychotic drugs in patients with DLB, their role in the treatment of psychiatric symptoms and behavioural problems is uncertain, although a small case report literature indicates that some patients may benefit. On the current balance of evidence, prescription of antipsychotic agents to patients with DLB is not recommended, although further studies focussing on patients with severe and intractable neuropsychiatric symptoms are required. Provisional case series indicate a high degree of motor response to levodopa therapy, although controlled trials are a priority to carefully evaluate the benefits in the context of possible adverse effects, such as the exacerbation of psychosis.
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PMID:Dementia with Lewy bodies: clinical features and treatment. 1141 14

Dementia with Lewy bodies (DLB) may include both Alzheimer and Lewy body pathology, but has never been reported to cause primary progressive aphasia. We report a 69-year-old woman who died 11 years after presenting with the syndrome of progressive aphasia. Six years after aphasia onset she developed visual hallucinations, and subsequently parkinsonism. Autopsy examination revealed Alzheimer's disease (AD), cortical Lewy bodies, and depigmentation and Lewy bodies in the substantia nigra and locus ceruleus. The aphasia most likely reflected the initial onset of AD, and the psychosis and parkinsonism most likely reflected the subsequent onset of Lewy body pathology. This first reported case of progressive aphasia occurring within the context of AD and Lewy body pathology uniquely illustrates the clinical and pathological nosological relationships between these two disease processes, and demonstrates a limitation of the general term, 'DLB'.
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PMID:Progressive aphasia with Lewy bodies. 1214 51


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