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

在美国，最近发现某些地区的居民更容易患上阿尔茨海默氏症 疾病(AD)和相关痴呆症与其他地区相比。然而，决定这一点的因素 地理上的差异尚不清楚。氡是一种无色、无味和放射性的气体，通过 进入家庭和其他建筑物的镭-226通过裂缝和穿透的放射性衰变 这座建筑的底座。研究已经将氡暴露与神经疾病的风险联系在一起，如 脑血管疾病或中风。此外，氡浓度与阿尔茨海默病死亡率显著相关。 美国不受年龄、高血压和糖尿病等传统风险因素的影响。氡气 暴露被认为在病理机制和健康方面与烟草吸烟相似。 对肺癌的影响。虽然氡与肺癌之间的因果关系很好 有文献记载，氡暴露如何影响认知的确切机制尚未明确阐明。 氡衰变后，血液、静脉、动脉和各种组织(包括大脑)中都可以检测到氡气。 产品被吸入。来自氡及其衰变产物的阿尔法粒子沿着它们的 会导致细胞和DNA损伤的追踪。此外，已经证明，氡及其衰变 在血流以及血管和脑组织中的产品，会诱导氧化应激和/或促进 炎症，这是痴呆症的危险因素。线粒体DNA拷贝数(MtDNAcn)，a 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 作为一种新的认知功能下降的生物标志物。在体外研究中，氡暴露导致线粒体功能障碍。 氡暴露引起的氧化应激也可能有助于线粒体的功能。最重要的是 该项目的目标是研究氡暴露与认知障碍和mtDNAcn之间的关系 美国的普通人口。为了达到研究目标，我们建议对原因进行辅助研究。 中风的地理和种族差异研究--一项以美国全国人口为基础的队列研究 非裔美国人和高加索成年人。具体地说，我们将研究住宅和 县级氡暴露并伴有认知障碍。此外，我们将调查这一关联 居室氡暴露和mtDNAcn之间的关系。根据美国环境保护署的说法 (EPA)，在美国，大约每15户家庭中就有1户的氡浓度超过EPA的氡浓度 4pci/L的行动水平，以及现代北美住宅内氡暴露的稳步上升 环境。由于大多数房屋在建造时并不防氡，因此人们暴露在氡中的风险更高。 现在比30年前估计的处于危险之中。这项研究的发现将为我们提供对 美国痴呆症或阿尔茨海默病的地理变异和种族差异，并可能确定共同的 这一全球主要致残健康状况的可修改风险因素。

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.