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)

We examine the evidence for free radical involvement and oxidative stress in the pathological process underlying Parkinson's disease, from postmortem brain tissue. The concept of free radical involvement is supported by enhanced basal lipid peroxidation in substantia nigra in patients with Parkinson's disease, demonstrated by increased levels of malondialdehyde and lipid hydroperoxides. The activity of many of the protective mechanisms against oxidative stress does not seem to be significantly altered in the nigra in Parkinson's disease. Thus, activities of catalase and glutathione peroxidase are more or less unchanged, as are concentrations of vitamin C and vitamin E. The activity of mitochondrial superoxide dismutase and the levels of the antioxidant ion zinc are, however, increased, which may reflect oxidative stress in substantia nigra. Levels of reduced glutathione are decreased in nigra in Parkinson's disease; this decrease does not occur in other brain areas or in other neurodegenerative illnesses affecting this brain region (i.e., multiple system atrophy, progressive supranuclear palsy). Altered glutathione metabolism may prevent inactivation of hydrogen peroxide and enhance formation of toxic hydroxyl radicals. In brain material from patients with incidental Lewy body disease (presymptomatic Parkinson's disease), there is no evidence for alterations in iron metabolism and no significant change in mitochondrial complex I function. The levels of reduced glutathione in substantia nigra, however, are reduced to the same extent as in advanced Parkinson's disease. These data suggest that changes in glutathione function are an early component of the pathological process of Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The Royal Kings and Queens Parkinson's Disease Research Group. 151 Mar 85

The management of dementia patients encompasses pharmacologic, behavioral, and psychosocial intervention strategies. Before pharmacologic intervention is instituted, it is important that sources of excess disability and comorbidity be eliminated or reduced. Identification of comorbid medical and psychiatric conditions, such as depression and delirium, should be identified and appropriately treated. Providing caregivers with education, support, and practical advice is a critical component of the management of the demented patient. The current standard of care for pharmacologic management of the cognitive and functional disabilities of AD consists of the combination of a cholinesterase inhibitor and high-dose vitamin E. This standard is based on the results of large-scale, double-blind, placebo-controlled trials. Cholinesterase inhibitors are the only FDA-approved pharmacologic treatments for AD. Cholinesterase inhibitors have been shown to be effective in the treatment of the cognitive, behavioral, and functional deficits of AD. Large-scale placebo-controlled trials of tacrine, donepezil, rivastigmine, and galantamine have demonstrated moderate benefits in patients with mild to moderate AD. Donepezil, rivastigmine, and galantamine are the first-line choices in the treatment of AD because of their lack of hepatotoxicity, ease of administration, few significant drug-drug interactions, and mild to moderate side effects. There are few contraindications to the use of cholinesterase inhibitors. Known hypersensitivity to a specific drug or its derivatives is the only true contraindication. Cautious administration of cholinesterase inhibitors is advised in patients who have a previous history of allergy or adverse reactions to prior cholinesterase inhibitors, severe liver disease, preexisting bradycardia, peptic ulcer disease, current alcoholism, asthma, or chronic obstructive pulmonary disease. Nausea, vomiting, diarrhea, and anorexia are the most common side effects of cholinesterase inhibitors. These gastrointestinal side effects can be minimized by gradual dose increases, administration with food, adequate hydration, and judicious use of an antiemetic. Vitamin E has been demonstrated to slow the progression of AD in several small and one large placebo-controlled trials. Because of its low cost and safety, it is recommended in addition to a cholinesterase inhibitor for the treatment of AD. There are no FDA-approved treatments for DLB and VaD. One small placebo-controlled trial demonstrated that rivastigmine may be effective in the treatment of DLB. More large-scale placebo-controlled trials are needed to confirm the results of this study. Treatment of VaD focuses on the control, identification, and management of cerebrovascular disease and vascular risk factors. Although there are no peer-reviewed reports on the efficacy of cholinesterase inhibitors for VaD or mixed AD/VaD, early reports suggest that these agents may also be effective for mixed AD/VaD. The indications for the use of cholinesterase inhibitor drugs are eventually likely to broaden to include DLB, mixed AD/VaD, and AD in its more advanced stages.
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PMID:Pharmacologic treatments of dementia. 1217 Oct 61

Parkinson's disease (PD) is the most common cause of parkinsonism. Parkinsonism is characterized by resting tremor, bradykinesia, rigidity and gait impairment. There is no specific diagnostic test for PD and it is important for clinicians to understand the clinical signs which help to distinguish PD from parkinsonism. It is equally important to be aware of the clinical signs which can be an indication that the diagnosis is not PD. These so-called Parkinson-plus syndromes include progressive supranuclear palsy (PSP), multiple systems atrophy (MSA), corticobasal degeneration (CBD), vascular parkinsonism (VP) and parkinsonism with dementia (Lewy body dementia, LBD). The differential diagnosis of parkinsonism will be discussed. Initiating pharmacologic therapy for PD must take into consideration the degree of dysfunction the patient is experiencing, the question of neuroprotection, the degree of motor response required, and the potential complications of long-term treatment. Neuropro-tective trials of coenzyme Q10 (CoQ), vitamin C, vitamin E, monoamine oxidase B inhibitors (MAO-I) and dopamine agonists do not support the use of any of these drugs for a neuroprotective effect. There is recent supportive evidence that levodopa may have a neuroprotective effect. Either dopamine agonists or levodopa may be initiated. Dopamine agonists are associated with fewer motor fluctuations and dyskinesias, while levodopa is associated with better motor performance. Initiation of therapy should be tailored to individual patients with the emphasis on symptom control, with the hope that new approaches to treatment of PD (including neuroprotection) will be forthcoming.
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PMID:Parkinson's disease. Diagnosis and the initiation of therapy. 1617 58

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review the evidence on the drug treatment for dementia. The level of evidence (types) was rated using a standard system: Types 1a and 1b (evidence from meta-analysis of randomised controlled trials or at least one controlled trial respectively); types 2a and 2b (one well-designed study or one other type of quasi experimental study respectively); type 3 (non-experimental descriptive studies); and type 4 (expert opinion). There is type 1a evidence for cholinesterase inhibitors (donepezil, rivastigmine and galantamine) for mild to moderate Alzheimer's disease; memantine for moderate to severe Alzheimer's disease; and for the use of bright light therapy and aromatherapy. There is type 1a evidence of no effect of anti inflammatory drugs or statins. There is conflicting evidence regarding oestrogens, with type 2a evidence of a protective effect of oestrogens but 1b evidence of a harmful effect. Type 1a evidence for any effect of B12 and folate will be forthcoming when current trials report. There is type 1b evidence for gingko biloba in producing a modest benefit of cognitive function; cholinesterase inhibitors for the treatment of people with Lewy body disease (particularly neuropsychiatric symptoms); cholinesterase inhibitors and memantine in treatment cognitive impairment associated with vascular dementia; and the effect of metal collating agents (although these should not be prescribed until more data on safety and efficacy are available). There is type 1b evidence to show that neither cholinesterase inhibitors nor vitamin E reduce the risk of developing Alzheimer's disease in people with mild cognitive impairment; and there is no evidence that there is any intervention that can prevent the onset of dementia. There is type 1b evidence for the beneficial effects of adding memantine to cholinesterase inhibitors, and type 2b evidence of positive switching outcomes from one cholinesterase inhibitor to another. There is type 2a evidence for a positive effect of reminiscence therapy, and type 2a evidence that cognitive training does not work. There is type 3 evidence to support the use of psychological interventions in dementia. There is type 2 evidence that a clinical diagnosis of dementia can be made accurately and that brain imaging increases that accuracy. Although the consensus statement dealt largely with medication, the role of dementia care in secondary services (geriatric medicine and old age psychiatry) and primary care, along with health economics, was discussed. There is ample evidence that there are effective treatments for people with dementia, and Alzheimer's disease in particular. Patients, their carers, and clinicians deserve to be optimistic in a field which often attracts therapeutic nihilism.
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PMID:Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. 1706 Mar 46