The study of the effects of pollutants is critically important for addressing the epochal challenges we face, as global populations are increasingly shifting from rural to urban centers, transforming our world into an urban world. These transformations will exacerbate pollution, thereby underscoring the need to uncover its impact on human health. Epidemiological studies have reported that pollution increases the risk of neurological diseases, with growing evidence for an elevated risk of neurodegenerative disorders. Air pollution and waterborne pollutants are the primary chemical agents driving this risk. These chemicals can promote inflammation, acting synergistically with genetic vulnerability. However, the biological underpinnings of this association remain unknown. In this review, we focus on the link between pollution and brain network connectivity at the macroscopic level. We provide an up-to-date overview of epidemiological findings and studies investigating pollution-related changes in brain networks, and we discuss mechanistic insights into pollution-induced brain changes through neural networks. We describe in detail the pollutome–connectome axis that could provide the functional substrate for pollution-induced processes leading to cognitive decline and neurodegeneration. We illustrate this framework in the context of two pollutants: air pollution, a widely recognized threat, and per- and polyfluoroalkyl substances, a broad class of synthetic chemicals currently emerging as a novel neurotoxic source.
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