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居民更有可能患有阿尔茨海默氏症 疾病（AD）和相关的痴呆症相比，在其他地区。然而，决定因素 地理差异尚不清楚。氡气是一种无色、无味的放射性气体，通过大气形成 镭-226的放射性衰变，通过裂缝和渗透进入家庭和其他建筑物， 大楼的底层结构研究表明，氡暴露与神经系统疾病的风险有关， 脑血管疾病或中风。此外，氡浓度与AD死亡率显著相关， 美国独立的一些传统的危险因素，如年龄，高血压和糖尿病。氡 在病理机制和健康方面，暴露被认为与吸烟相似 对肺癌的影响。氡与肺癌之间的因果关系 尽管有文献记载，但氡暴露如何影响认知的确切机制尚未明确阐明。 氡衰变后，在血液、静脉、动脉和各种组织（包括大脑）中可检测到氡气 产品被吸入。氡及其衰变产物产生的α粒子沿其自身的轨道沿着产生密集电离。 这可能会导致细胞和DNA损伤。此外，已证明氡及其衰变 产品，在血流以及血管和脑组织，诱导氧化应激和/或促进 炎症，这是痴呆症的危险因素。此外，线粒体DNA拷贝数（mtDNA Acn）， 线粒体数量和功能以及氧化应激水平的标志物，已经被提出 作为认知能力下降的新生物标志物。在体外研究中，氡暴露诱导线粒体功能障碍。 氡暴露引起的氧化应激也可能影响线粒体功能。总体 本项目的目的是研究氡暴露与认知障碍和线粒体DNA的关系， 美国一般人口。为达致研究目的，我们建议进行一项辅助研究， 卒中的地理和种族差异（REGARDS）研究-一项基于美国全国人群的队列研究 非裔美国人和白人成年人。具体来说，我们将研究住宅和 县级氡暴露伴认知功能障碍。此外，我们还将调查 住宅氡暴露和线粒体DNA之间的关系据美国环境保护署 (EPA)在美国，大约每15个家庭中就有一个的氡浓度超过了美国环保署的氡浓度。 行动水平为4 pCi/L，在现代北美住宅中，氡暴露量稳步上升 环境由于大多数房屋都没有防氡建筑，人们面临更高的氡暴露风险 比30年前估计的要危险。这项研究的结果将提供深入了解 在美国痴呆症或AD的地理变异和种族差异，并可能确定一个共同的 这一全球主要致残性健康状况的可改变风险因素。