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.

Radon is a colorless, odorless, toxic radioactive gas and radon exposure is common and rising steadily within the modern North American residential environment. The proposed study aims to examine the associations of radon exposure with cognitive impairment and mitochondrial function, a biomarker of cognitive impairment, in the US general population. Since randomized clinical trials on radon exposure is not feasible, findings from this study will provide insights into the geographic variation and racial disparity of dementia or Alzheimer’s disease in the US and potentially identify a common modifiable risk factor for this major disabling health condition.