A systematic review of associations between the environment, DNA methylation, and cognition

The increasing prevalence of neurodegenerative diseases poses a significant public health challenge, prompting a growing focus on addressing modifiable risk factors of disease (e.g. physical inactivity, mental illness, and air pollution). The environment is a significant contributor of risk factors which are known to impact the brain and contribute to disease risk (e.g. air pollution, noise pollution, green and blue spaces). Epigenetics can offer insights into how various environmental exposures impact the body to contribute to cognitive outcomes. In this systematic review, we examined studies which have associated an environmental exposure to a type of epigenetic modification, DNA methylation, and a cognitive outcome. We searched four databases with keywords "environmental exposures," "epigenetics," and "cognition." We yielded 6886 studies that we screened by title/abstract followed by full text. We included 14 studies which focused on four categories of environmental exposure: air pollution (n = 3), proximity to roads (n = 1), heavy metals (n = 6), and pesticides (n = 4). Overall, n = 10/14 studies provided evidence that DNA methylation is statistically significant in the association between the environment and a cognitive outcome. Furthermore, we identified that n = 5/14 studies performed a type of biological pathway analysis to determine the presence of biological pathways between their environmental exposure and cognitive outcome. Our findings underscore the need for methodological improvements and considerations in future studies, including investigation of other environmental exposures considering tissue-specificity of methylation profiles and stratifying analysis by sex, ethnicity and socioeconomic determinants of disease. This review demonstrates that further investigation is warranted, the findings of which may be of use in the development of preventative measures and risk management strategies for neurodegenerative disease.