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)

Parkinson's disease (PD) is one of the major neurological diseases affecting elderly subjects. Presumed prevalence of PD is 80-100 per 100 thousands and it is estimated that there are approximately 100 thousands patients in Japan. From a statistic on age distribution of patients visiting doctors, it is estimated that patients with ages at 75-79(639/100,000) and 80-84(632/100,000) are highest in number. Juvenile parkinsonism is a syndrome with parkinsonian motor symptoms and dystonia developing before and after ten years of age. Reports on this syndrome have been accumulated in Japan and gene abnormality in a enzyme relating to dopamine metabolism was discovered in the hereditary progressive dystonia with marked diurnal fluctuation (Segawa). Among symptomatic parkinsonism, cerebrovascular parkinsonism is mainly due to multiple infarction in the basal ganglia or Binswanger's disease in Japan, and both conditions develops parkinsonism, pseudobulbar palsy and dementia progressively. Diffuse Lewy body disease and a unique type of progressive supranuclear palsy presenting a disorder designated "pure akinesia" were studied mainly in Japan. In drug therapies of PD, it has been argued why the maintenance dose of levodopa or dopamine agonists was generally low in Japan. In addition to constitution and drug metabolism, attitude of Japanese people to worry side effects more than merit with beneficial effects by a drug may have inevitably lead to low maintenance dose. Development of new drugs have been undertaken in parallel with US and Europe. Talipexole hydrochloride has been on market in Japan recently, but MAO-B inhibitors and COMT inhibitors are in final stages to wait evaluations by the governmental committee.
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PMID:[Clinical characteristics and trends in research of Parkinson's disease and parkinsonism in Japan]. 901 16

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

Cognitive abnormalities are common in Parkinson's disease, with important social and economic implications. Factors influencing their evolution remain unclear but are crucial to the development of targeted therapeutic strategies. We have investigated the development of cognitive impairment and dementia in Parkinson's disease using a longitudinal approach in a population-representative incident cohort (CamPaIGN study, n = 126) and here present the 5-year follow-up data from this study. Our previous work has implicated two genetic factors in the development of cognitive dysfunction in Parkinson's disease, namely the genes for catechol-O-methyltransferase (COMT Val(158)Met) and microtubule-associated protein tau (MAPT) H1/H2. Here, we have explored the influence of these genes in our incident cohort and an additional cross-sectional prevalent cohort (n = 386), and investigated the effect of MAPT H1/H2 haplotypes on tau transcription in post-mortem brain samples from patients with Lewy body disease and controls. Seventeen percent of incident patients developed dementia over 5 years [incidence 38.7 (23.9-59.3) per 1000 person-years]. We have demonstrated that three baseline measures, namely, age >or=72 years, semantic fluency less than 20 words in 90 s and inability to copy an intersecting pentagons figure, are significant predictors of dementia risk, thus validating our previous findings. In combination, these factors had an odds ratio of 88 for dementia within the first 5 years from diagnosis and may reflect the syndrome of mild cognitive impairment of Parkinson's disease. Phonemic fluency and other frontally based tasks were not associated with dementia risk. MAPT H1/H1 genotype was an independent predictor of dementia risk (odds ratio = 12.1) and the H1 versus H2 haplotype was associated with a 20% increase in transcription of 4-repeat tau in Lewy body disease brains. In contrast, COMT genotype had no effect on dementia, but a significant impact on Tower of London performance, a frontostriatally based executive task, which was dynamic, such that the ability to solve this task changed with disease progression. Hence, we have identified three highly informative predictors of dementia in Parkinson's disease, which can be easily translated into the clinic, and established that MAPT H1/H1 genotype is an important risk factor with functional effects on tau transcription. Our work suggests that the dementing process in Parkinson's disease is predictable and related to tau while frontal-executive dysfunction evolves independently with a more dopaminergic basis and better prognosis.
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PMID:The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. 1981 13