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)

Depression, hallucinations, psychosis and cognitive deficits may often complicate advanced Parkinson's disease. Their detection and treatment have extraordinary importance, as they may cause significant invalidity and even an increase in mortality. Optimization of antiparkinsonian therapy may exert a positive influence on depressive symptoms, and should therefore be performed before antidepressant drugs are started. On the other hand, hallucinations and dementia do usually benefit from a discontinuation or dosage reduction of anticholinergic drugs, selegiline, DA-agonists and amantadine. When a levodopa monotherapy is indicated, slow-release formulations should be avoided. When a neuroleptic treatment is needed, clozapine and maybe quetiapine should be preferred. Preliminary evidence suggests that cholinesterase inhibitors might partially improve cognitive deficits in Parkinson's disease.
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PMID:[Psychological and cognitive problems in Parkinson disease--therapeutic possibilities]. 1193 48

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

In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmacology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.
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PMID:A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials. 1211 73

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

Although Alzheimer's disease, Parkinson's disease, and motor neurone disease are distinct disorders, there could be a common neurodegenerative mechanism that characterises the death of selective neurone populations in each case. We propose that this mechanism could be an aberrantly activated, developmental process involving a non-classical, non-enzymatic action of acetylcholinesterase mediated via a short linear motif near the C-terminal end of the molecule. Since this motif has a highly conserved homology with part of the amyloid precursor protein, it may be particularly attractive as a target for novel therapeutic strategies in neurodegeneration.
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PMID:Parkinson's disease, Alzheimer's disease and motor neurone disease: identifying a common mechanism. 1215 Jul 69

A new method for quantitative measurement of brain acetylcholinesterase (AChE) activity in living human brain using positron emission tomography (PET) is described. We tested several radiolabeled lipophilic acetylcholine analogs, e.g., N-methylpiperidyl esters, which readily entered the brain via the blood-brain barrier, were hydrolyzed selectively by AChE, and were then trapped in the brain. Among them, and tested and N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) was chosen as the tracer for PET. Quantitative measurement of cortical AChE was accomplished by fitting the time course of cerebral radioactivity concentration measured by PET and the metabolite-corrected arterial plasma input function using a nonlinear least-squares fitting method. Normal control studies of subjects with a wide range in age (24-89 years) showed no decrease in AChE activity in the cerebral cortex with age. Studies on patients with Alzheimer's disease demonstrated a widespread reduction of AChE activity in the cerebral cortex (more profound in early-onset than in late-onset Alzheimer's disease). Parkinson's disease and progressive supranuclear palsy, clinically similar disorders, could be differentiated with [11C]MP4A/PET studies. Simple methods without using an arterial input function are also proposed. The method provides a quantitative measure of the cholinergic aspect of brain function and proved to be useful in diagnosis of neurodegenerative disorders including Alzheimer's disease.
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PMID:Positron emission tomography: quantitative measurement of brain acetylcholinesterase activity using radiolabeled substrates. 1218 13

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

Common to all subtypes of dementia, including Alzheimer's disease (AD), and those associated cerebrovascular disease (CVD), Lewy body pathology and Parkinson's disease, is degeneration of cholinergic neurotransmission. The cholinergic hypothesis of AD is based on evidence of reduced cholinergic markers and decreased numbers of cholinergic neurons and nicotinic acetylcholine receptors (nAChR) in the hippocampus and cortex of the brain-both areas associated with memory, learning and executive function impairments characteristic of cognitive decline in AD. There is growing evidence for the involvement of the cholinergic system in vascular dementia (VaD). Attention has, therefore, recently turned to the use of cholinergic treatments such as galantamine (Reminyl), which has demonstrated broad-spectrum and long-term efficacy in AD, for the treatment of patients with VaD or AD with CVD. Galantamine is both a moderate, reversible, competitive acetylcholinesterase inhibitor, and an allosteric modulator of nAChR. Recent evidence suggests that the unmatched efficacy of galantamine in cognitive as well as behavioral and functional symptoms in patients with AD, as well as those with VaD or AD with CVD, may at least partly result from its unique dual cholinergic mode of action. Here, the rationale for using galantamine to treat dementia related to CVD is discussed. In particular, some interesting findings are covered which indicate the potential of galantamine to modulate other neurotransmitter systems (e.g. serotonergic, dopaminergic), which may be of specific relevance in the behavioral symptoms of dementia related to CVD.
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PMID:The rationale behind cholinergic drug treatment for dementia related to cerebrovascular disease. 1241 71

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


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