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)

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

Dementia with Lewy bodies appears to be the second most common form of dementia, accounting for about one in five cases. The condition is characterized by dementia accompanied by delirium, visual hallucinations, and parkinsonism. Other common symptoms include syncope, falls, sleep disorders, and depression. The presence of both Lewy bodies and amyloidplaques with deficiencies in both acetylcholine and dopamine neurotransmitters suggests that dementia with Lewy bodies represents the middle of a disease spectrum ranging from Alzheimer's disease to Parkinson's disease. The diagnosis of dementia with Lewy bodies is based on clinical features and exclusion of other diagnoses. Individualized behavioral, environmental, and pharmacologic therapies are used to alleviate symptoms and support patients and their families. Cholinesterase inhibitors are more effective in patients who have dementia with Lewy bodies than in those with Alzheimer's disease. Conversely, patients who have dementia with Lewy bodies do not respond as well to antiparkinsonian medications. Anticholinergic medications should be avoided because they exacerbate the symptoms of dementia. Traditional antipsychotic medications can precipitate severe reactions and may double or triple the rate of mortality in patients who have dementia with Lewy bodies.
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PMID:Dementia with Lewy bodies: an emerging disease. 1662 10

Cholinesterase inhibition in patients with Alzheimer's disease (AD) may affect heart rate, sometimes inducing bradycardia. Additional cardiac safety considerations apply in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PDD), in whom cardiovascular autonomic nervous system dysfunction is common. We conducted a review of the safety data available for rivastigmine in these two conditions. A modest reduction in the mean heart rate of 1.5-2 bpm was seen. No clinically meaningful treatment differences in bradycardia or ECG abnormalities were apparent. Compared with placebo, rivastigmine appeared to be associated with fewer vascular disorder adverse events (AEs) (p = 0.002) and fewer AEs of syncope (p = 0.018) in PDD patients (n = 541). A smaller randomised, placebo-controlled study of rivastigmine in DLB (n = 120) showed similar findings. Rivastigmine appears to have a favourable cardiac safety profile in PDD and DLB patients.
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PMID:Cardiac safety of rivastigmine in Lewy body and Parkinson's disease dementias. 1680 45

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are pathological overlapping and important causes of dementia for which clinical trials are in their infancy. Cholinesterase inhibitors may be of benefit in DLB and PDD, as suggested by placebo-controlled clinical trials of rivastigmine and donepezil. The anti-psychotic agent clozapine has been of benefit in PD and PDD, but other agents, such as quetiapine, require adequate assessment. Barriers to trials include pathological overlap that can lead to inaccuracies in clinical diagnosis, unavailability of a consensus definition for PDD, unanswered questions regarding natural history and the paucity of validated outcome measures. Motor impairment must be considered in patients with PDD and DLB; conversely, cognitive impairment should be assessed in trials targeting motor impairment in advanced PD. Potential targets for treatment include onset of dementia, cognitive impairment, behavioral impairment, functional decline, falls, nursing home placement, mortality, quality of life and economic impact. Biomarkers including neuroimaging and cerebrospinal fluid markers are not currently established. At present PDD and DLB are distinct entities by definition. Future studies, including clinical trials and biomarker studies, will help to further define the clinical and therapeutic implications of this distinction.
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PMID:Clinical trials in Parkinson's disease dementia and dementia with Lewy bodies. 1746 93

I report here clinical effects of cholinesterase inhibitors (rivastigmine and donepezil) on visual hallucinations emerging in the course of Parkinson's disease (PD) and clinically unresponsive to antipsychotics. Five patients with PD (with or without dementia) complicated by visual hallucinations and unresponsive to atypical antipsychotics were offered a 12-week, open-label trial of a cholinesterase inhibitor. All 5 subjects completed the trial with no major adverse effects and, of note, no discontinuations due to adverse events. Visual hallucinations resolved in 4 subjects and were markedly diminished in one person. Neither changes in UPDRS scores nor exaggeration of subjective complaints about extrapyramidal symptoms were noted during treatment. Cholinesterase inhibitors might represent a useful alternative to antipsychotics for patients with PD accompanied by visual hallucinations even in the absence of dementia. One must, however, not forget that their use with this indication remains experimental and safety measures as well as accurate clinical surveillance are of crucial importance.
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PMID:Parkinson's disease-related visual hallucinations unresponsive to atypical antipsychotics treated with cholinesterase inhibitors: a case series. 1762 23

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past 15 years, from an initial interpretation of symptoms as dopaminergic drug adverse effects to the current view of a complex interplay of extrinsic and disease-related factors.PD psychosis has unique clinical features, namely that it arises within a context of a clear sensorium and retained insight, there is relative prominence of visual hallucinations and progression occurs over time. PD psychosis tends to emerge later in the disease course, and disease duration represents one risk factor for its development. The use of anti-PD medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for PD psychosis. Other risk factors discussed in the literature include older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression.Recent efforts have aimed to explore the complex pathophysiology of PD psychosis, which is now known to involve an interaction between extrinsic, drug-related and intrinsic, disease-related components. The most important extrinsic factor is use of dopaminergic medication, which plays a prominent role in PD psychosis. Intrinsic factors include visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); neurochemical (dopamine, serotonin, acetylcholine, etc.) and structural abnormalities involving site-specific Lewy body deposition; and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype). Preliminary reports have also shown a potential relationship between deep brain stimulation surgery and PD psychosis.When reduction in anti-PD medications to the lowest tolerated dose does not improve psychosis, further intervention may be warranted. Several atypical antipsychotic agents (i.e. clozapine, olanzapine) have been shown to be efficacious in reducing psychotic symptoms in PD; however, use of clozapine requires cumbersome monitoring and olanzapine leads to motor worsening. Studies of ziprasidone and aripiprazole are limited to open-label trials and case reports and are highly variable; however, it appears that while each may be effective in some patients, both are associated with adverse effects. While quetiapine has not been determined efficacious in two randomized controlled trials, it is a common first-line treatment for PD psychosis because of its tolerability, ease of use and demonstrated utility in numerous open-label reports. Cholinesterase inhibitors currently represent the most promising pharmacological alternative to antipsychotics. Tacrine is rarely tried because of hepatic toxicity, and controlled trials with donepezil have not shown significant reductions in psychotic symptoms, due perhaps to methodological limitations. However, results from an open-label study and a double-blind, placebo-controlled trial involving 188 hallucinating PD patients support the efficacy of rivastigmine. With regard to non-pharmacological interventions, case reports suggest that electroconvulsive therapy has the potential to reduce psychotic symptoms and may be considered in cases involving concurrent depression and/or medication-refractory psychosis. Limited case reports also suggest that specific antidepressants (i.e. clomipramine and citalopram) may improve psychosis in depressed patients. Finally, studies in the schizophrenia literature indicate that psychological approaches are effective in psychosis management but, to date, this strategy has been supported only qualitatively in PD, and further studies are warranted.
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PMID:Pathophysiology and treatment of psychosis in Parkinson's disease: a review. 1866 59

The pharmacotherapy of Parkinson disease dementia and Lewy body dementia with cholinesterase inhibitors and selected psychotropic drugs is relatively new. Review of literature supplemented by expert opinion. Cholinesterase inhibitors can be used by primary care practitioners and specialists, with often clinically meaningful results. Primary care practitioners play an essential role in the diagnosis and management of patients with these conditions.
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PMID:Pharmacotherapy of Parkinson disease dementia and Lewy body dementia. 1918 71

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use.
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PMID:Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology. 2108 41

Dementia more than one year after the onset of motor features associated with Parkinson's disease is defined as Parkinson's disease with dementia (PDD). If it develops within one year of the motor features, the term dementia with Lewy bodies (DLB) is used. Since clinical and pathological features are similar, it is generally accepted that both represent a continuum of the same disorder. PDD together with DLB account for around one fifth of all cases of dementia in the elderly. Studies suggest that most patients with Parkinson's disease would eventually develop dementia if they lived long enough. The diagnosis of PDD in the presence of long-standing pronounced motor features rarely poses a diagnostic dilemma. However, the diagnosis of DLB may be more difficult. It relies on the revised consensus clinical criteria which require the presence of at least two of the following three syndromes: persistent visual hallucinations, fluctuating defects in cognitive and functional ability, and parkinsonism. An early referral to a specialist clinic may not only help to confirm the diagnosis, but also to co-ordinate the group of professionals working with the patient. Well lit rooms and the use of glasses and hearing aids can help to reduce hallucinations. Cholinesterase inhibitors used in Alzheimer's disease have a role in DLB and PDD. Trials show moderate improvements in cognitive function in patients treated with rivastigmine. The greatest impact, however, seems to be on the psychotic features of the disease. Patients with DLB are less likely to have a good motor response from L-dopa than patients with Parkinson's disease or PDD.
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PMID:Tackling dementia in patients with Parkinson's disease. 2137 Jul 9

Dementia with Lewy-bodies (DLB) and Parkinson's disease dementia (PDD) are no rare causes of dementia. Both have neuropathologically, clinically, and neurochemically much in common. In the course of both conditions frequently psychotic symptoms occur, often induced by antiparkinsonian medication. Treatment of psychotic features with conventional antipsychotics is not tolerated in many cases. Therefore low-dose clozapine treatment is acknowledged usual practise for psychosis in Parkinson's disease and a case report indicates efficacy for psychosis in DLB, too. All other atypical antipsychotics except risperidone are not licensed for dementia in Germany, but risperidone is contraindicated in DLB due to manufacturer's notice and usually not well tolerated in DLB and Parkinson's disease. Open trials indicate safety for treatment of psychosis in DLB and PDD with quetiapine. Randomized controlled trials indicate, that quetiapine is less effective than clozapine against psychotic symptoms in both conditions, although comparatively safe. Cholinesterase inhibitors, especially rivastigmine, are a therapeutic alternative for treating both psychotic and cognitive symptoms in both conditions. Parkinsonism in DLB-patients responds worse to levodopa compared to patient with Parkinson's disease. Anticholinergic drugs often induce delirium in demented patients and therefore should be avoided. The same problem is associated with dopamine agonists in PDD and DLB. Amantadine, a NMDA-receptor antagonist like memantine, potentially bears the same risk of worsening psychotic symptoms. The following preliminary recommendation for drug treatment of PDD and DLB can be given: Stop all anticholinergic medication and reduce levodopa and other antiparkinsonian medication to the tolerated minimum. Levodopa alone is preferred. Treat with cholinesterase inhibitors to the maximum tolerated dose. If there is no adequate response regarding psychotic symptoms, add quetiapine. If this approach fails, replace quetiapine by low-dose clozapine. If behavioural disturbances are due to depression, anxiety, or irritability, treatment with an antidepressant, preferably citalopram, is an option.
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PMID:[Drug treatment of dementia with Lewy bodies and Parkinson's disease dementia--common features and differences]. 2142 15


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