Exploring the epigenome to identify biological links between the urban environment and neurodegenerative disease: an evidence review

Global urbanisation has occurred in tandem with population ageing, having implications on human cognitive health. Urban environmental factors such as air pollution are known risk factors of cognitive impairment and neurodegenerative disease. However, due to the sparse evidence base, the biological pathways by which urban environmental factors operate are not well understood. The aim of this review is to explain how exploring the epigenome (i.e. chemical modifications to the genome which do not change the underlying gene sequence) can further our understanding of these biological pathways. The epigenome is influenced by environmental factors and has implications for cognitive impairment and neurodegenerative disease. Utilising complex epigenetic analytical techniques including epigenetic clocks, Mendelian randomization and multi-omic approaches, it is possible to identify environmental consequences on underlying biology. Through better understanding of how epigenetic modifications, which can be inherited or change dynamically in response to environmental exposures, impact cognitive outcomes, we can work to encourage the development of public health policies, as well as urban planning and design policies to reduce the burden of neurodegenerative disease and encourage healthier ageing in the older adult population.