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)

The objective of this study was to assess the tolerability and efficacy of rivastigmine in a group of patients with probable dementia with Lewy bodies (DLB), using an open label study. Open label treatment was with rivastigmine up to maximum tolerated dose (mean 9.6 mg daily, range 3-12 mg). Eleven patients with DLB, mean age 78.5 years, were treated with this cholinesterase inhibitor. After 12 weeks of treatment, mean Neuropsychiatric Inventory scores fell by 73% for delusions, 63% for apathy, 45% for agitation and 27% for hallucinations. Five of the patients (45%) experienced very significant clinical improvements that had not been achieved with other treatments, including low dose neuroleptics. Medication was well tolerated and parkinsonian symptoms tended to improve. Cholinesterase inhibition may be a safe and effective alternative to neuroleptic treatment in DLB. Such effects may also prove to be applicable to the management of neuropsychiatric symptoms in Parkinson's disease and Alzheimer's disease.
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PMID:Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. 1082 36

Glutamate is the major excitatory neurotransmitter of the central nervous system. Besides its importance in many physiological processes, increased glutamate release and subsequent excessive stimulation of the various glutamate receptors are thought to play critical roles in the pathophysiological mechanisms underlying many neurologic diseases. Experimental data suggest that blockade of glutamate receptors or inhibition of glutamate release has positive effects in many disease models. Glutamate antagonists are already in clinical use for the treatment of Parkinson's disease, epilepsy, spasticity, and neuropathic pain. Overall, glutamate antagonists have not been found clinically effective for neuroprotective treatment of cerebral ischemia or chronic neurodegenerative diseases, with one exception. Side effects of glutamate antagonists can be mainly attributed to central mechanisms and include psychosis, agitation, and disorientation. It is to be hoped that further development of new glutamate antagonists that block disease-relevant subtypes of glutamate receptors will lead to more effective drugs with fewer side effects.
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PMID:[Glutamate antagonists in neurology]. 1143 98

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

We report a sporadic case of unusual cerebral amyloid angiopathy (CAA) with prominent capillary involvement. A 67-year-old doctor developed gait disturbance, resting tremor and rigidity. He was diagnosed to have Parkinson's disease, for which the treatment with levodopa was effective. Four years later he began to exhibit progressive cognitive decline and behavioral abnormalities consisting of hallucination and agitation. Subsequently, his condition steadily worsened and became bedridden with severe dementia, and he died eight years after the disease onset. During the clinical course, there had been no episode of stroke. Postmortem examinations revealed the typical pathology of Parkinson's disease with frequent cortical Lewy bodies in the amygdala. The most striking pathological feature of this patient was widespread CAA where prominent beta-amyloid (A beta) deposition was observed in the capillaries of the neocortex, most pronouncedly in the occipital lobe, as well as leptomeningeal and cerebral medium-sized and small vessels. Further, perivascular plaques were found in half of the amyloid-laden capillaries. Tau-positive dystrophic neurites were only sparsely detectable within a few perivascular plaques. Despite the severe A beta pathology, there was no microaneurysmal dilatation, fibrinoid necrosis or vascular occlusion. There was only one small ischemic lesion in the brain. The cerebral white matter was unremarkable. Senile plaques of neuritic type and neurofibrillary tangles were mostly limited to the hippocampal regions and, to a lesser degree, in the amygdaloid nucleus, which did not meet the neuropathological criteria of Alzheimer's disease. On the gene analyses, his apolipoprotein E (ApoE) genotyping was verified to be heterozygous epsilon 3/epsilon 4, and no mutation was seen in exons 16 and 17 of the amyloid precursor protein gene. Severe A beta capillary angiopathy as seen in our patient is exceptional in sporadic CAA. Further, A beta angiopathy of this patient was notable in the absence of an associated cerebrovascular disease despite prominent A beta deposition in the vessel walls. Regarding the development of his severe dementia, the limbic pathology of Lewy body disease might be one of the potential causes, but A beta angiopathy appears more likely because of its severity. We speculate that widespread A beta deposition disregulates the blood-brain barrier of the capillaries leading to a disturbance of the microcirculation throughout the cerebral cortex without obvious ischemic disintegration of the neuropil. We should take into consideration that A beta angiopathy can present as progressive dementia without cerebrovascular disease.
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PMID:[Sporadic cerebral amyloid angiopathy presenting with dementia and prominent capillary beta-amyloid deposition: a case report]. 1260 81

Alpha-synuclein is a presynaptic protein that has been implicated as a possible causative agent in the pathogenesis of Parkinson's disease. The native protein is a major component of nigral Lewy bodies in Parkinson's disease, and full-length alpha-synuclein accumulates in Lewy neurites. Here we present evidence that alpha-synuclein levels are elevated in midbrain dopamine (DA) neurons of chronic cocaine abusers. Western blot and immunoautoradiographic studies were conducted on postmortem neuropathological specimens from cocaine users and age-matched drug-free control subjects. The results demonstrated that alpha-synuclein levels in the DA cell groups of the substantia nigra/ventral tegmental complex were elevated threefold in chronic cocaine users compared with normal age-matched subjects. The increased protein levels in chronic cocaine users were accompanied by changes in the expression of alpha-synuclein mRNA in the substantia nigra and ventral tegmental area. Although alpha-synuclein expression is prominent in the hippocampus, there was no increase in protein expression in this brain region. The levels of beta-synuclein, a possible negative regulator of alpha-synuclein, also were not affected by cocaine exposure. Alpha-synuclein protein levels were increased in the ventral tegmental area, but not the substantia nigra, in victims of excited cocaine delirium who experienced paranoia, marked agitation, and hyperthermia before death. The overexpression of alpha-synuclein may occur as a protective response to changes in DA turnover and increased oxidative stress resulting from cocaine abuse. However, the accumulation of alpha-synuclein protein with long-term cocaine abuse may put addicts at increased risk for developing the motor abnormalities of Parkinson's disease.
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PMID:Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons. 1268 41

Parkinson's disease is a neuropsychiatric disease with multiple psychic disorders. They mainly result from a combination between neuropathogical lesions and antiparkinsonian drugs. The most frequent psychic disorders are depression and psychosis. So far, pharmacological treatments of depression has been poorly evaluated. It is suggested that the first-line treatment of depression in Parkinson's disease is the class of the Selective Serotonin Reuptake Inhibitors. The occurrence of worsening in parkinsonism and agitation in rare cases necessitates a meticulous clinical follow-up. The treatment of psychosis is based on the reduction of antiparkinsonian medications, by tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. When psychosis persists despite a simple levodopa monotherapy, then an antipsychotic drug is added. Clozapine is the only officially approved drug for psychosis in Parkinson's disease. Two double blind studies showed a clear antipsychotic effect without worsening of parkinsonism. Quetiapine, another atypical neuroleptic drug without risk of blood dyscrasia may prove to be as effective than clozapine. Olanzapine and risperidone can aggravate parkinsonism and should be used only as a last resort. Future studies will precise the place of anticholinesterases in the treatment of psychosis associated with dementia.
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PMID:[Psychic disorders] 1269 Mar 23

Parkinson's disease is a neuropsychiatric disease with multiple psychic disorders. They mainly result from a combination between neuropathological lesions and antiparkinsonian drugs. The most frequent psychic disorders are depression and psychosis. So far, pharmacological treatments of depression has been poorly evaluated. It is suggested that the first-line treatment of depression in Parkinson's disease is the class of the Selective Serotonin Reuptake Inhibitors. The occurrence of worsening in parkinsonism and agitation in rare cases necessitates a meticulous clinical follow-up. The treatment of psychosis is based on the reduction of antiparkinsonian medications, by tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. When psychosis persists despite a simple levodopa monotherapy, then an antipsychotic drug is added. Clozapine is the only officially approved drug for psychosis in Parkinson's disease. Two double blind studies showed a clear antipsychotic effect without worsening of parkinsonism. Quetiapine, another atypical neuroleptic drug without risk of blood dyscrasia may prove to be as effective than clozapine. Olanzapine and risperidone can aggravate parkinsonism and should be used only as a last resort. Future studies will precise the place of anticholinesterases in the treatment of psychosis associated with dementia.
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PMID:[Psychic disorders]. 1269 Jun 72

The continuance of sexual expression in the elderly as age advances is well recognized. Sexual disinhibition, however, in a restricted environment such as in nursing care facilities has received scant attention. We wish to describe eight patients residing in nursing care facilities who were seen because of their problematic sexually related behaviors. These behaviors include cuddling, touching of the genitals, sexual remarks propositioning, grabbing and groping, use of obscene language and masturbating without shame. In all instances concern emanated from members of the nursing staff. Other associated behaviors included aggression, agitation, and irritability amongst others. The computed tomography (CT) scan of the brain showed infarction in the frontal lobe (4), parietal lobe (1), and the caudate (1). One had severe Parkinson's Disease and one had severe dementia of the Alzheimer's disease. All ten patients had an organic basis for their symptoms. Sexually inappropriate behaviors remain highly controversial and labeling them as 'diseased' or an 'illness' may have enormous individual, cultural and medico-legal implications. The clinico-anatomical correlation are discussed.
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PMID:Hypersexuality in nursing care facilities--a descriptive study. 1476 58

Neurodegenerative diseases are increasingly common in elderly patients, who present a particular anaesthetic challenge. The majority of people over the age of 70 years have some degree of cerebral atrophy. The pathogenesis of neurodegenerative diseases is due to alterations in the transport, degradation and aggregation of proteins. Alterations in physiology that occur with advancing age affect both the pharmacokinetics and pharmacodynamics of drugs used in the elderly. Changes in pharmacokinetics result in either increased or reduced drug concentrations depending on the variable contributions of absorption, metabolism and elimination. The distribution of a drug depends on its protein binding, cardiac output and blood volume, which are all altered in the elderly. Metabolism and excretion of drugs are also affected due to changes in hepatic and renal mass and blood flow in the elderly. A number of drugs are used in neurodegenerative disorders including antidepressants, benzodiazepines, antipsychotics, acetylcholinesterase inhibitors and levodopa. Polypharmacy is a common problem, which can lead to adverse drug interactions and an exacerbation of dementia. Levodopa, bromocriptine and tricyclic antidepressants are known to cause orthostatic hypotension in patients with neurodegenerative disease. Elderly patients are liable to excessive sedation from benzodiazepines in both the pre- and postoperative period; therefore these drugs should be prescribed in low doses. For induction of general anaesthesia propofol is a suitable agent in patients with neurodegenerative disease due to its rapid metabolism, but may not be suitable in patients with Parkinson's disease as it can induce spontaneous involuntary movements. Volatile inhalational agents should be administered carefully in the elderly, as they are more sensitive to the depressant cerebral and cardiovascular effects. Levodopa should be avoided in conjunction with halothane, which sensitises the heart to catecholamines. Co-administration of monoamine oxidase inhibitors and opioids should be avoided as it can cause agitation, muscular rigidity, sweating and hyperpyrexia. If an anticholinergic agent is required, then glycopyrronium bromide is the drug of choice in this group of patients, as it does not cross the blood brain barrier. Patients should continue to take their usual medications in hospital and do not let the change in routine alter the times at which treatments are administered. This is particularly relevant to the timing of levodopa in Parkinson's disease, as missed treatment can be detrimental. Regional anaesthesia may, however, have significant advantages in patients with Parkinson's disease, who can continue to take oral levodopa preoperatively, during surgery, if required, and early in the postoperative period. Anti-emetic drugs such as phenothiazines, butyrophenones and metoclopramide should be used carefully in the postoperative period in these patients as their antidopaminergic effects may induce or exacerbate parkinsonian effects.
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PMID:Anaesthesia in elderly patients with neurodegenerative disorders: special considerations. 1501 69

Psychotic symptoms are common and can be a major therapeutic challenge in patients with Parkinson's disease (PD). PD-related psychosis is usually characterized by visual hallucinations or delusions and is most often induced by antiparkinsonian medications. However, other medical conditions, psychoactive medications, sleep disturbances, mood disorders, and cognitive impairments are relevant risk factors. Patients with PD should be continually monitored for factors that can trigger the development of psychotic symptoms, including minor symptoms. This includes ongoing critical re-evaluation of the therapeutic regimen, with adjustments as indicated to optimize function across motor, cognitive, and psychiatric domains. Treatment strategies to reduce psychotic symptoms are determined by the clinical picture. "Benign" symptoms may require only education and reassurance. Antipsychotic medications are required for disabling symptoms and emergency hospitalization may be required for agitation that affects the safety of the patient or others. Medication management is often complex and includes elimination or reduction of antiparkinsonian agents (although this can compromise motor function), management of medical comorbidities, and use of atypical antipsychotics. Clozapine and quetiapine are regarded as the most safe and effective atypical neuroleptics in PD patients. Cholinesterase inhibitors can enhance cognition and may reduce psychotic symptoms.
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PMID:Psychosis in Parkinson's Disease. 1504 1


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