The association between air pollutants and hippocampal volume from magnetic resonance imaging: A systematic review and meta-analysis

Growing epidemiological evidence suggests that air pollution may increase the risk of cognitive decline and neurodegenerative disease. A hallmark of neurodegeneration and an important diagnostic biomarker is volume reduction of a key brain structure, the hippocampus. We aimed to investigate the possibility that outdoor air nitrogen dioxide (NO₂) and particulate matter with diameter ≤2.5 μm (PM_2.5) and ≤10 μm (PM₁₀) adversely affect hippocampal volume, through a meta-analysis. We considered studies that assessed the relation between outdoor air pollution and hippocampal volume by structural magnetic resonance imaging in adults and children, searching in Pubmed and Scopus databases from inception through July 13, 2021. For inclusion, studies had to report the correlation coefficient along with its standard error or 95% confidence interval (CI) between air pollutant exposure and hippocampal volume, to use standard space for neuroimages, and to consider at least age, sex and intracranial volume as covariates or effect modifiers. We meta-analyzed the data with a random-effects model, considering separately adult and child populations. We retrieved four eligible studies in adults and two in children. In adults, the pooled summary β regression coefficients of the association of PM_2.5, PM₁₀ and NO₂ with hippocampal volume showed respectively a stronger association (summary β -7.59, 95% CI -14.08 to -1.11), a weaker association (summary β -2.02, 95% CI -4.50 to 0.47), and no association (summary β -0.44, 95% CI -1.27 to 0.40). The two studies available for children, both carried out in preadolescents, did not show an association between PM_2.5 and hippocampal volume. The inverse association between PM_2.5 and hippocampal volume in adults appeared to be stronger at higher mean PM_2.5 levels. Our results suggest that outdoor PM_2.5 and less strongly PM₁₀ could adversely affect hippocampal volume in adults, a phenomenon that may explain why air pollution has been related to memory loss, cognitive decline, and dementia.