Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last six years, eight new substances for the treatment of idiopathic parkinsonism (IP) have been approved for use: four oral and one parenteral dopamine agonist (apomorphine), two COMT-inhibitors and budipine. The old drug amantadine has experienced a renaissance in the treatment of a complication occurring during long-term treatment of IP, namely levodopa-induced dyskinesia. Deep brain stimulation with programmable pulse generators and stereotactically implanted electrodes are increasingly being used in patients with severe on-off phases and levodopa dyskinesia. The treatment of Parkinson's disease unresponsive to dopaminergic substances and that associated with dementia remains problematical. In combinations of parkinsonism and dementia, the cholinesterase inhibitors are being used in particular for Lewy body dementia.
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PMID:[Dopaminergic agents, COMT inhibitors or amantadine? Proper treatment for your Parkinson patient]. 1207 Aug 48

As cholinergic mechanisms may be at least partially responsible for hallucinations and delusions in Parkinson's disease (PD), we conducted an open study in 8 PD patients to assess the efficacy and tolerability of the cholinesterase inhibitor donepezil, 5 mg at bedtime for two months, in the treatment of these complications. Hallucinations and delusions improved significantly in all patients. Donezepil was overall well tolerated, but a deterioration in motor disability was noted in 2 out of 8 patients.
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PMID:Donepezil in the treatment of hallucinations and delusions in Parkinson's disease. 1211 20

Multiple behavioural and psychological symptoms of dementia (BPSD) are commonly associated with all dementia subtypes, and worsen during disease progression. BPSD arise due to impairment of cholinergic function in the cortex, hippocampus and related limbic systems. Recent studies have investigated the effect of cholinesterase inhibitors on BPSD. The dual acetylcholinesterase/butyrylcholinesterase (AChE/BuChE) inhibitor rivastigmine was shown to have several potential advantages over the AChE-selective inhibitors donepezil and galantamine for the treatment of BPSD. Rivastigmine appears to be effective across the range of dementia severity from mild to severe, and across the spectrum of dementia (Alzheimer's disease [AD], the AD variant with Lewy bodies, Parkinson's disease dementia and vascular dementia subtypes). It also appears to have a disease-modifying potential. Rivastigmine improved a wider range of behavioural symptoms (apathy, anxiety/depression, hallucinations and delusions) than donepezil and galantamine (which improved apathy and depression/anxiety only). Unlike donepezil, rivastigmine reduced the need for psychotropic medications to treat BPSD. Dual inhibition of AChE and BuChE and brain-region selectivity through preferential inhibition of the G1 isoform of AChE may provide the underlying reasons for the apparently greater and broader efficacy of rivastigmine over AChE-selective inhibitors for the treatment of BPSD. However, randomised, controlled trials are required to compare dual inhibitors, such as rivastigmine, and AChE-selective agents, to confirm and quantify any differences in their effects on BPSD.
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PMID:The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia. 1213 65

Parkinson's disease patients may suffer from cognitive impairment and behavioural problems such as apathy, personality changes, speech disturbances and visual hallucinations (Parkinson's disease dementia). However, there is currently no recommended treatment for Parkinson's disease dementia and antipsychotic agents can worsen extrapyramidal symptoms, making them unsuitable for patients with this condition. The observation that patients with Parkinson's disease dementia have extensive cholinergic deficits led to the hypothesis that cholinesterase inhibitors may provide benefits for patients with this condition. Here, we present a case series of patients with Parkinson's disease and dementia who we treated with rivastigmine, a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) that shows brain region-selectivity. The introduction of rivastigmine led to improvements in cognitive and functional abilities, as well as the resolution of behavioural problems and visual hallucinations. Rivastigmine was well tolerated by our patients when the dose was escalated slowly, including one patient who had previously experienced severe side-effects with the AChE-selective inhibitor donepezil. Despite the large number and range of concomitant medications being received by the patients, no side-effects thought to be related to drug-drug interactions were reported. A large, placebo-controlled study is warranted to ascertain the full clinical profile of rivastigmine in Parkinson's disease dementia.
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PMID:Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson's disease: a case series. 1224 Jul 87

Cholinesterase inhibitors are licensed for treatment of dementia in Alzheimer's disease. However, the effects of these drugs on the cognitive symptoms of dementia are very small. We suggest that symptoms like impairment of attention and concentration, anxiety, restlessness and hallucinations, delineate a specific central cholinergic deficiency syndrome (CDS), that may be a much better target for such treatment. Changes in the quantitative electroencephalogram, muscarinic subtype radioimaging and serum anticholinergic activity may potentially help to diagnose the CDS. CDS is suggested to occur in various neurodegenerative diseases like Alzheimer's disease, Lewy body dementia and Parkinson's disease and to respond well to cholinesterase inhibitor therapy.
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PMID:The cholinergic deficiency syndrome and its therapeutic implications. 1245 52

Alzheimer's disease is the most common cause of dementia, but Parkinson's disease also shows dementia in the later stages. Donepezil is a cholinesterase inhibitor used for the treatment of Alzheimer's disease. Variable responses to this drug suggest that Alzheimer's disease is clinically heterogeneous. In the clinical trial of tacrine, a first developed cholinesterase inhibitor, three cases markedly improved and, several years later, they were pathologically confirmed as dementia with Lewy bodies (DLB). In recent years, another cholinesterase inhibitor, rivastigmine, has also been reported to be effective for patients with DLB by a placebo-controlled, double-blind, multicenter study. Parkinson's disease with dementia, which is known to fulfill the pathological criteria of DLB, also shows a favorable response to donepezil. In some cases, not only does cognitive function improve, but also parkinsonism. Both DLB and Parkinson's disease with dementia show characteristic CBF patterns: While the parietal and temporal lobes are involved in Alzheimer's disease, the occipital lobe is additionally affected in these diseases. Alzheimer's disease and Parkinson's disease have been considered discrete disease entities. However, viewed from the aspects of response to donepezil treatment and CBF patterns, both diseases overlapped. A brain SPECT may be a useful tool to detect such treatable conditions.
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PMID:Responses to donepezil in Alzheimer's disease and Parkinson's disease. 1248 Jul 91

The objective was to summarize recent findings about the clinical features, diagnosis and investigation of dementia with Lewy (DLB) bodies, together with its neuropathology, neurochemistry and genetics. Dementia with Lewy bodies (DLB) is a primary, neurodegenerative dementia sharing clinical and pathological characteristics with both Parkinson's disease (PD) and Alzheimer's disease (AD). Antiubiquitin immunocytochemical staining, developed in the early 1990s, allowed the frequency and distribution of cortical LBs to be defined. More recently, alpha-synuclein antibodies have revealed extensive neuritic pathology in DLB demonstrating a neurobiological link with other "synucleinopathies" including PD and multiple system atrophy (MSA). The most significant correlates of cognitive failure in DLB appear to be with cortical LB and Lewy neurites (LNs) rather than Alzheimer type pathology. Clinical diagnostic criteria for DLB, published in 1996, have been subjected to several validation studies against autopsy findings. These conclude that although diagnostic specificity is high (range 79- 100%, mean 92%), sensitivity is lower (range 0- 83 %, mean, 49%). Improved methods of case detection are therefore required. Fluctuating impairments in attention, visual recognition and construction are more indicative of DLB than AD. Relative preservation of medial temporal lobe volume on structural MRI and the use of SPECT tracers for regional blood flow and the dopamine transporter are the most reliable current biomarkers for DLB. There are no genetic or CSF tests recommended for the diagnosis of DLB at present. Between 15 and 20% of all elderly demented cases reaching autopsy have DLB, making it the most common cause of degenerative dementia after AD. Exquisite, not infrequently fatal, sensitivity to neuroleptic drugs and encouraging reports of the effects of cholinesterase inhibitors on cognitive, psychiatric and neurological features, mean that an accurate diagnosis of DLB is more than merely of academic interest. Dementia developing late in the course of PD shares many of the same clinical and pathological characteristics.
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PMID:Dementia with Lewy bodies. 1256 32

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

This review provides an overview of the three most widely used cholinesterase (ChE) inhibitors: donepezil, rivastigmine, and galantamine. Differences in pharmacologic profiles will be discussed, and consideration will be given to how such differences may relate to and influence the clinical efficacy and tolerability of the various agents. In addition to providing cognitive benefits in patients with Alzheimer's disease (AD), growing clinical evidence also suggests that ChE inhibitors can produce favorable and clinically relevant effects on neuropsychiatric/behavioral disturbances and activities of daily living. Furthermore, recent data indicate that these agents may be effective at all levels of disease severity and for all rates of disease progression. The clinical utility of ChE inhibitors in a wider spectrum of dementias which share a common cholinergic deficit, such as Lewy body dementia, Parkinson's disease dementia, and vascular dementia, is currently under investigation. Beyond symptomatic relief, data suggest that ChE inhibitors may also slow the underlying disease process. As clinical and research experience with these agents continues to accumulate, the differences in their effects will become more apparent and will help physicians tailor ChE inhibition treatment to the needs of the individual patient.
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PMID:A clinical overview of cholinesterase inhibitors in Alzheimer's disease. 1263 82

Traditionally, the neuropsychiatric symptoms of Alzheimer's disease (AD) have been managed with neuroleptics or benzodiazepines, which have serious side effects. Preliminary observations suggest the possible value of cholinesterase inhibitors in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer's type, dementia with Lewy bodies, and in patients with Parkinson's disease. Twelve inpatients with AD with psychotic symptoms and lack of improvement of their delusions/hallucinations during perphenazine treatment (8 mg/day) for 3 weeks received random open-label donepezil 5 mg daily in addition to an ongoing treatment of 8 mg/day perphenazine or 16 mg/day perphenazine. Assessments conducted at baseline and after weeks 2 and 4 included the Mini-Mental State Examination, the Global Deterioration Scale, the Positive and Negative Symptoms Scale, and the Clinical Global Impressions scale. Frequency of extrapyramidal symptoms was measured according to the Abnormal Involuntary Movement Scale. The donepezil-perphenazine group exhibited substantially greater and clinical improvements in mental state. At the end of the trial (4 weeks), Positive and Negative Symptoms Scale scores revealed significant differences between both groups (p = 0.006). The Clinical Global Impressions scale and the Mini-Mental State Examination scores also showed significant differences between the donepezil-perphenazine group and the perphenazine group (p = 0.028 and p = 0.027 respectively). No significant differences were found in the Global Deterioration Scale scores. Abnormal Involuntary Movement Scale scores showed a significant deterioration in extrapyramidal symptoms in the perphenazine group compared with the donepezil-perphenazine group (p = 0.016). Donepezil augmentation of neuroleptics may be appropriate for those patients for whom neuroleptic monotherapy either does not lead to symptom remission or is associated with intolerable adverse effects. This was an open-label study and there is need for larger studies with double-blind control and a long-term study design to define the efficacy of donepezil for patients with AD and psychotic symptoms.
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PMID:Donepezil as add-on treatment of psychotic symptoms in patients with dementia of the Alzheimer's type. 1267 28


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