Environmental Epidemiology of Essential Tremor

特发性震颤的环境流行病学

• 批准号: 8262158
• 负责人: ELAN D LOUIS
• 金额: $ 56.16万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8262158
• 关键词: Address; African; Age; Alzheimer' s Disease; Attention; Autopsy; Biological; Biological Assay; Blood; Blood specimen; Brain; Brain Diseases; Brain region; Caucasians; Caucasoid Race; Cerebellum; Chickens; Clinic; Collection; Communities; Connecticut; Data; Degenerative Disorder; Diet; Dietary Factors; Disease; Dystonia; Elderly; Enrollment; Environmental Epidemiology; Environmental Risk Factor; Epidemiologic Studies; Essential Tremor; Etiology; Fishes; Frequencies; Gender; Genes; Geographic Locations; Goals; Hand; Hour; Human; Incidence; Individual; Indoles; Institutes; Intention Tremor; Israel; Italy; Laboratory Animals; Lead; Life; Link; Location; Manganese; Measures; Meat; Medical center; Meleagris gallopavo; Methods; Monozygotic Twinning; Monozygotic twins; Neurologic; Neurotoxins; New Jersey; New York; Occupational; Organ; Organic solvent product; Parkinson Disease; Pathology; Patients; Persons; Pesticides; Play; Population; Prevalence; Process; Publishing; Purkinje Cells; Race; Recording of previous events; Reporting; Research; Research Infrastructure; Resources; Risk Factors; Role; Sample Size; Sampling; Series; Severities; Singapore; Source; Spain; Swelling; Time; Tissues; Torpedo; Toxic Environmental Substances; Toxin; Tremor; Twin Studies; United States; Universities; Vegetables; West Bank; Woman; aged; base; beef; case control; cohort; disorder prevention; disorder risk; harman; interest; kindred; men; mind control; nervous system disorder; non-genetic; population based; prevent; programs; repository; sample collection; toxicant

Essential tremor (ET) is the most common cause of tremor in humans yet its etiology remains unclear. Environmental toxicants are likely to contribute to its etiology. Such factors are thought to play an important role in other neuro-degenerative diseases,but their role in ET has received less attention. During the last eight years (2000 - 2008), we have studied several putative toxicants. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is the most promising early candidate in the search for environmental risk factors for ET. During the past three years (2005 - 2008), we studied several potential mechanisms that could underlie elevated blood harmane concentrations in our clinic-based sample of ET cases in New York. These studies suggest that dietary factors might play a role. In tandem with these studies, we have continued to collect blood harmane samples in New York. Moving forward, our goal is to now definitely establish the links between this neurotoxin and ET. This is a five-year competitive renewal in which we propose to address four inter-related questions. First, although elevated harmane concentrations have been observed in ET cases in blood, brain concentrations of this neurotoxin have not been investigated. ET is a brain disease and the brain is the presumed target organ of this neurotoxin. Are harmane concentrations elevated in the ET brain (Specific Aim 1)? Second, our finding was derived from a single study of ET cases primarily from one tertiary referral center in New York. If one were to sample a group of ET cases ascertained in a completely different manner (i.e., community-based) half-way around the world, would one find an elevated blood harmane concentration (Specific Aim 2)? Third, our finding of an elevated harmane concentration was a cross-sectional observation, sampling blood at a single time point. It is not clear whether these same ET cases would persist in demonstrating elevated blood harmane concentrations if re-assessed at a second time point several years later (Specific Aim 3)? Finally, one study found elevated blood harmane concentrations in Parkinson's disease, raising the question as to whether elevated blood harmane is specifically linked with ET or is merely a more general, global marker of neurological illness (Specific Aim 4)? Approximately 50% of ET cases are non-familial. Given its population prevalence of 4.0% in persons age > 40 years, then 2.0% of the population aged > 40 years has a non-familial form of ET, yet the environmental underpinnings for this tremor are just beginning to be explored. Identification and understanding of these toxicants is the first step in preventing a progressive neurological disease with few treatment options.

特发性震颤（ET）是人类震颤的最常见原因，但其病因仍不清楚。 环境毒物可能是其病因。这些因素被认为是重要的 在其他神经退行性疾病中的作用，但它们在ET中的作用受到的关注较少。在过去的八年里， 2000 - 2008年，我们研究了几种假定的有毒物质。Harmane（1-甲基-9H-吡啶并[3，4-B]吲哚）是 在寻找ET的环境风险因素中最有希望的早期候选者。在过去三 2005年至2008年，我们研究了几种可能导致血液中有害物质升高的潜在机制。 我们在纽约的ET病例的临床样本中的浓度。这些研究表明饮食因素 可能会发挥作用。在这些研究的同时，我们继续在纽约收集血液harmane样本， 约克。展望未来，我们的目标是现在明确建立这种神经毒素和ET之间的联系。这是一 五年竞争性续约，我们建议解决四个相互关联的问题。一是虽然 在ET病例中，已经观察到升高的哈烷浓度， 神经毒素尚未研究。ET是一种脑部疾病，大脑是其假定的靶器官。 神经毒素ET脑中的哈满浓度是否升高（具体目标1）？其次，我们的发现是， 来源于主要来自纽约一个三级转诊中心的ET病例的单一研究。如果要 对一组以完全不同的方式确定的ET病例进行采样（即，以社区为基础） 在全球范围内，是否会发现血中哈尔烷浓度升高（具体目标2）？第三，我们的发现 在一个时间点采集血液样本，进行横断面观察。 目前尚不清楚这些ET病例是否会持续显示血胆固醇升高 如果在几年后的第二个时间点重新评估浓度（具体目标3）？最后，一项研究 发现帕金森氏病患者血液中的哈尔曼浓度升高，这就提出了一个问题， 升高的血液哈曼素与ET特异性相关，或者仅仅是一种更普遍的全球性标志物， 神经系统疾病（具体目标4）？大约50%的ET病例是非家族性的。鉴于其人口 如果年龄> 40岁的人的患病率为4.0%，则年龄> 40岁的人口中有2.0%患有非家族性 虽然这是ET的一种形式，但这种震颤的环境基础才刚刚开始探索。识别 了解这些有毒物质是预防进展性神经系统疾病的第一步， 治疗方案。