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)

Changes in cognitive function and disturbances in behavior are commonly seen in parkinsonian patients and they are inherent features of the disease. Estimates on the prevalence of dementia in this disorder are quite variable, ranging from 15 to 25%. Advanced age, depression, severity of akinesia, and the presence of dopaminomimetic psychosis, are considered as risk factors in the development of cognitive deterioration within this patient population. Cognitive dysfunction may manifest as relatively circumscribed deficits or overt dementia. The finding of mild cognitive deficits is common in Parkinson's disease, such as reduced flexibility, psychomotor slowing, reduction in learning capacity and information retrieval, and disturbances in visuospatial tasks. The most prevalent cognitive disturbance is an impairment in visuospatial tasks, not necessarily related to the degree of motor disability. Dementia, when present early on in the course of the disease may suggest alternative diagnoses (Diffuse Lewy body dementia, Alzheimer's disease with extrapyramidal features, Fronto-temporal dementia, etc.), while in those cases in whom the dementing disorder develops at a later stage, it is assumed to be an integral part of the disease, albeit corresponding to variable pathogenetic mechanisms.
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PMID:[Dementia and cognitive impairment in Parkinson disease]. 1240 19

BACKGROUND: Lewy body disease is, after Alzheimer's disease, the second most common cause of senile degenerative dementia with progressive cognitive deterioration, fluctuation of cognitive and motoric functions and psychotic symptoms. It is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. The aim of this study was to measure the cortical glucose metabolism using FDG PET (2-[18F]fluoro-2-deoxy-D-glucose position emission tomography) compared to normal subjects. PATIENTS AND METHODS: Five patients (5 m, mean age 75 y) with clinically suspected diffuse Lewy body disease (DLB) were studied with FDG PET. PET studies of the head were performed with a Siemens ECAT-ART PET-scanner with attenuation correction using 137-Cs point sources. RESULTS: We found the same distribution pattern of diffuse glucose hypometabolism in the entire cortical region with relative sparing of the primary sensory-motor cortex in all the patients. The few cases reported in the literature so far describe findings similar to ours. CONCLUSION: The pattern of diffuse glucose hypometabolism in the entire cortex including the occipital region seems to be a typical feature of DLB that is distinctive from dementia of Alzheimer's disease.
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PMID:Assessment of diffuse Lewy body disease by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET). 1262 39

Behavioral and psychological symptoms of dementia (BPSD) are a common manifestation of Alzheimer's disease (AD) and other dementia syndromes. Patients experience prominent and multiple symptoms, which are both distressing and a source of considerable social, health, and economic cost. Development of symptoms is in part related to progressive neurodegeneration and cholinergic deficiency in brain regions important in the regulation of behavioral and emotional responses including the cortex, hippocampus, and limbic system. Cholinesterase (ChE) inhibitors offer a mechanism-based approach to therapy to enhance endogenous cholinergic neurotransmission. Studies using ChE inhibitors have demonstrated their clear potential to improve or stabilize existing BPSD. Differences have been noted between selective acetylcholinesterase (AChE) inhibitors (donepezil and galantamine) and dual ChE inhibitors (rivastigmine) in terms of treatment response. While donepezil has shown efficacy in moderate to severe noninstitutionalized AD patients, conflicting results have been obtained in mild to moderate patients and in nursing home patients. Galantamine has been shown to delay the onset of BPSD during a five-month study but has been otherwise poorly studied to-date. Both donepezil and galantamine have not as yet demonstrated efficacy in reducing psychotic symptoms or in reducing levels of concomitant psychotropic medication use. Studies with the dual ChE inhibitor rivastigmine in mild to moderately severe AD and in Lewy body dementia (LBD) have shown improvements in behavioral symptoms including psychosis. Improvements have been maintained over a period of up to two years. In addition, institutionalized patients with severe AD have shown symptomatic benefits with a reduction in the requirement for additional psychotropic drugs following treatment with rivastigmine. The psychotropic properties associated with rivastigmine may in part be mediated through effects on butyrylcholinesterase. Current treatment options are limited for patients with dementia syndromes other than AD. However, data concerning rivastigmine in patients with LBD and preliminary studies in Parkinson's disease dementia and vascular dementia suggest a role for ChE inhibitors across the spectrum of dementia syndromes. Finally, studies that incorporated a delayed start design demonstrate that ChE inhibitors may delay the progression of BPSD.
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PMID:The ABC of Alzheimer's disease: behavioral symptoms and their treatment. 1263 79

Dementia with Lewy bodies (DLB) accounts for 15-20% of all autopsy confirmed dementias in old age. Characteristic histopathological changes are intracellular Lewy bodies and Lewy neurites, with abundant senile plaques but sparse neurofibrillary tangles. Core clinical features are fluctuating cognitive impairment, persistent visual hallucinations and extrapyramidal motor symptoms (parkinsonism). One of these core features has to be present for a diagnosis of possible DLB, and two for probable DLB. Supportive features are repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, delusions and hallucinations in other modalities. DLB is clinically under-diagnosed and frequently misclassified as systemic delirium or dementia due to Alzheimer's disease or cerebrovascular disease. Therapeutic approaches to DLB can pose difficult dilemmas in pharmacological management. Neuroleptic medication is relatively contraindicated because some patients show severe neuroleptic sensitivity, which is associated with increased morbidity and mortality. Antiparkinsonian medication has the potential to exacerbate psychotic symptoms and may be relatively ineffective at relieving extrapyramidal motor symptoms. Recently there is converging evidence that treatment with cholinesterase inhibitors can offer a safe alternative for the symptomatic treatment of cognitive and neuropsychiatric features in DLB. This review will focus on the clinical characteristics of DLB, its differential diagnosis and on possible management strategies.
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PMID:Dementia with lewy bodies--diagnosis and treatment. 1270 40

THE MAJOR THERAPEUTIC TRENDS: The treatment of psychosis in late life depends on the etiology of the delusion but also on its behavioral consequences (agitation, aggressiveness). We distinguish between the treatment of long term old psychosis and delusions occurring late in life (after the age of 60). FOR THE OLD PSYCHOSES: The reduction in the symptomatology often permits a reduction in the doses and the relay to atypical neuroleptics with improved tolerance. FOR DELUSIONS OCCURRING LATE IN LIFE: The treatment will be adjusted to the etiology of the delusion: delirious states associated with dementia, thymus delusion, schizophrenic or non-schizophrenic psychosis, delusion related to cerebral-vascular disorders or to sensorial dysafferentation. One should note that emotional and delusional disorders are often concomitant in the elderly. THE TWO TREATMENT AXES: The first therapeutic element is non-pharmacological: reassurance or even brief psychotherapy, family counseling and prevention of enhancing, notably environmental, factors. The pharmacological element preferably includes atypical anti-psychotics, antidepressants in some cases together with anti-epileptics in cases of concomitant rebellious aggressiveness. In cases of dementia with cholinergic deficiency (Alzheimer, Lewy body dementia, mixed dementia) cholinesterase inhibitors have demonstrated their efficacy on the hallucinations. Advice for a pertinent strategy of action should be provided.
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PMID:[Delirious states in elderly persons. Therapeutic modalities]. 1285 35

Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.
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PMID:Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy brain bank. 1450 69

Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.
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PMID:Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms. 1526 67

Dementia with Lewy bodies results from the accumulation from Lewy-type pathology (Lewy bodies, Lewy neurites), secondary cellular injury, and apoptotic neurodegeneration. The severity of dementia correlates with the abundance of Lewy bodies in the cortex. Dementia with Lewy bodies co-occurs with 2 specific syndromes, one beginning with dementia complicated by visual hallucinations and parkinsonism; the other beginning with Parkinson's disease and progressing to a parkinsonian-dementia syndrome. Clinical syndromes associated with these 2 pathways to dementia share many clinical features including the type of cognitive impairment, fluctuating attentional disturbances, prominent visual hallucinations and psychosis, depression, and rapid eye movement sleep behavior disorder. Lewy pathology results from protein misfolding and the accumulation of alpha-synuclein in the cell cytoplasm. Dementia with Lewy bodies is one of many neurodegenerative disorders linked to protein misfolding. Identification of clinical symptoms indicative of the presence of a specific protein disturbance will assist in choosing therapies when protein-specific disease-modifying treatments are available. Classification systems based on symptom complexes related to the presence of protein misfolding will assist therapeutic decisions.
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PMID:Dementia with lewy bodies: molecular pathogenesis and implications for classification. 1531 74

Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
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PMID:The neuropsychiatry of Parkinson's disease and related disorders. 1555 Feb 93

Dementia with Lewy bodies (DLB) is known for its partial resistance and hypersensitivity to some treatments, but DLB is treatable with cholinesterase inhibitors, sometimes better than in Alzheimer's disease. Cholinesterase inhibitors have a symptomatic effect on cognition and behavior. Nevertheless, new antipsychotics are sometimes also useful to manage psychotic symptoms. Although DLB patients respond less well to levodopa than patients with Parkinson's disease, 75 percent of DLB patients improve with levodopa, which is the best-tolerated dopaminergic agent. Nonpharmacological strategies include speech therapy, physiotherapy, psychotherapy, and educational support groups for care givers.
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PMID:[Treatment of dementia with Lewy bodies]. 1644 31


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