Radon exposure in relation to the risk of cognitive impairment and mitochondrial function

氡暴露与认知障碍和线粒体功能风险相关

• 批准号: 10591204
• 负责人: Ka Kahe
• 金额: $ 239.62万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591204
• 关键词: Adult; Affect; African American; Age; Air; Alpha Particles; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease related dementia; American; Ancillary Study; Area; Arteries; Biological Markers; Blood; Blood Vessels; Brain; Brain Neoplasms; Caucasians; Cerebrovascular Disorders; Chile; Cognition; Cognitive deficits; Country; County; DNA Damage; DNA copy number; Death Rate; Dementia; Diabetes Mellitus; Disease; District of Columbia; Dose; Environment; Environmental Risk Factor; Exposure to; Female; Functional disorder; Future; Gases; General Population; Goals; Health; Home; Housing; Human; Hypertension; Impaired cognition; In Vitro; Individual; Inflammation; Inhalation; Italy; Link; Malignant neoplasm of lung; Measures; Mitochondria; Mitochondrial DNA; Modernization; Modification; Neurodegenerative Disorders; New Zealand; Oxidative Phosphorylation; Oxidative Stress; Oxidative Stress Induction; Pathologic; Penetration; Persons; Proteins; Radioactive; Radium; Radon; Reasons for Geographic And Racial Differences in Stroke; Reporting; Research; Research Personnel; Resistance; Review Literature; Risk; Risk Factors; Scotland; Source; Stream; Stroke; Sweden; Tissues; Tobacco smoking behavior; United States Environmental Protection Agency; Veins; Visit; brain tissue; burden of illness; cancer risk; cell injury; cognitive change; cohort; dementia risk; effective therapy; energy balance; experience; follow-up; geographic difference; high risk; insight; ionization; male; mitochondrial dysfunction; modifiable risk; mortality; nervous system disorder; novel marker; population based; racial disparity; randomized, clinical trials; systematic review

In the US, it has been recently found that inhabitants in certain areas are more likely to have Alzheimer’s disease (AD) and related dementias compared to those in the other areas. However, the determinants for this geographic variation are unclear. Radon is a colorless, odorless, and radioactive gas formed through the radioactive decay of radium-226, which enters homes, and other buildings, through cracks and penetrations in the building’s substructure. Studies have linked radon exposure to the risk of neurological disorders such as cerebrovascular diseases or stroke. Also, radon concentrations are significantly correlated with AD mortality in the US independent of some traditional risk factors such as age, hypertension and diabetes mellitus. Radon exposure is considered to be similar to tobacco smoking in terms of pathologic mechanism and its health impact regarding lung cancer. While the causal association between radon and lung cancer is well documented, the exact mechanisms how radon exposure may affect cognition has not been clearly elucidated. Radon gas is detectable in the blood, veins, arteries and various tissues including the brain after radon decay products are inhaled. The alpha particles from radon and its decay products impart dense ionization along their track that can lead to cell and DNA damage. In addition, it has been demonstrated that radon and its decay products, in the blood stream as well as vascular and brain tissue, induce oxidative stress and/or promote inflammation, which are risk factors for dementia. Moreover, mitochondrial DNA copy number (mtDNAcn), a marker for both mitochondrial quantity and function as well as for oxidative stress levels, has been suggested as a novel biomarker for cognitive decline. In vitro studies, radon exposure induced mitochondrial dysfunction. Oxidative stress induced by radon exposure could also contribute to mitochondrial function. The overarching goal of this project is to examine the association of radon exposure with cognitive impairment and mtDNAcn in the US general population. To achieve the research goal, we are proposing an ancillary study in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study – an US national population-based cohort of African American and Caucasian adults. Specifically, we will examine the associations of residential and county-level radon exposure with cognitive impairment. Additionally, we will investigate the association between residential radon exposure and mtDNAcn. According to the US Environmental Protection Agency (EPA), approximately 1 out of every 15 homes in the US has radon concentrations exceeding the EPA’s Radon Action Level of 4 pCi/L, and radon exposure is rising steadily within the modern North American residential environment. Because most homes are not built radon-resistant, people are at higher risk of radon exposure now than had been estimated to be at risk 30 years ago. Findings from this study will provide insights into the geographic variation and racial disparity of dementia or AD in the US and potentially identify a common modifiable risk factor for this major global disabling health condition.

在美国，最近发现某些地区的影响者更有可能拥有阿尔茨海默氏症 与其他地区相比，疾病（AD）和相关痴呆症。但是，确定词为此 地理变化尚不清楚。 ra是一种无色的，无味的和放射性气的 通过裂缝和穿透进入，进入房屋和其他建筑物的放射性腐烂，进入家园和其他建筑物 该建筑物的子结构。研究已将ra暴露与神经系统疾病的风险（例如 脑血管疾病或中风。同样，ra浓度与AD死亡率显着相关 美国独立于一些传统的危险因素，例如年龄，高血压和糖尿病。氡 就病理机制及其健康而言，暴露被认为与吸烟相似 有关肺癌的影响。虽然ra和肺癌之间的因果关系很好 证明，确切的机制可能影响认知的确切机制尚未清楚地阐明。 在血液，静脉，动脉和各种组织中，可以检测到ra剂气体，包括ra衰变后的大脑 产品被吸入。 ra的α颗粒及其衰减产物沿其沿其衰减的产物散发着致密的电离 跟踪会导致细胞和DNA损伤的轨迹。此外，已经证明ra及其衰变 产物，在血液以及血管和脑组织中，诱导氧化应激和/或促进 炎症，是痴呆症的危险因素。此外，线粒体DNA拷贝数（mtdnaCn），a 已经提出了线粒体数量和功能以及氧化应激水平的标记物 作为认知能力下降的新型生物标志物。体外研究，ra暴露会诱导线粒体功能障碍。 ra暴露引起的氧化应激也可能有助于线粒体功能。总体 该项目的目标是检查ra暴露与认知障碍和mtdnaCn的关联 美国普通人群。为了实现研究目标，我们提出了一项辅助研究的原因 对于中风（问起）的地理和种族差异 - 美国国家人口的同类 非裔美国人和高加索成年人。具体而言，我们将研究居民的协会和 县级ra暴露有认知障碍。此外，我们将调查协会 在居民之间，ra暴露和mtdnacn。根据美国环境保护局的说法 （EPA），美国每15所房屋中约有1个具有超过EPA ra的ra浓度 在现代北美居民中，动作水平为4 PCI/L，ra暴露在稳步上升 环境。因为大多数房屋不是耐药的，所以人们暴露ra的风险较高 现在比估计30年前处于危险之中。这项研究的发现将为您提供见解 在美国，痴呆症或AD的地理差异和种族差异，并有可能确定一个常见 这种主要的全球残疾健康状况的可修改风险因素。