The mediating role of inflammation and oxidative stress, as well as vascular-related factors, in the association between air pollution and dementia or related cognitive outcomes: A systematic review

Background: Air pollution is a growing global concern and has now been identified as a significant risk factor for dementia. While the mechanisms underlying this relationship remain unclear, inflammation and oxidative stress, as well as vascular-related factors have been hypothesised as being involved. Objective: This systematic review aimed to investigate these factors as potential mediators between particulate matter air pollution and dementia or related cognitive outcomes. Methods: This review was registered with PROSPERO. A systematic search of Medline, Embase, PsycINFO, and grey literature was conducted in May 2024, adhering to the PRISMA guidelines. Results: Of 1098 articles retrieved, 14 studies met the inclusion criteria, involving a total of 143,124 participants. The majority of studies investigated vascular-related factors (n = 12), a smaller number examined inflammation and oxidative stress (n = 5). A meta-analysis was not performed due to high study heterogeneity in terms of exact exposures, mediators, and outcomes. Some evidence suggested that hypertension may partially mediate the association between indoor air pollution and cognitive decline, and stroke may contribute to the impact of air pollution on dementia risk. However, the evidence for both was conflicting and limited. No consistent evidence supported the involvement of other mediators. Conclusions: Due to the limited studies undertaken, there is insufficient evidence about whether inflammation and oxidative stress, or vascular-related factors mediate the effects of air pollution on dementia and related cognitive outcomes. Further longitudinal studies are needed to address this research gap, elucidate the underlying mechanisms, enhance disease understanding, and inform prevention and risk reduction strategies.