Association between exposure to air pollution and prefrontal cortical volume in adults: A cross-sectional study from the UK biobank
Introduction
Neurodegenerative disease is a major global-health concern, with an estimated 47 million people worldwide in 2015 having Alzheimer's disease (Livingston et al., 2017), a type of neurodegeneration. In addition to genetic risk factors, numerous environmental factors, some of which are potentially modifiable, have been associated with Alzheimer's disease (Livingston et al., 2017; Xu et al., 2015). Further, several different brain regions are associated with neurodegenerative diseases including the prefrontal cortex. In addition to the involvement of the prefrontal in neurodegenerative diseases such as frontal-temporal neurodegeneration (Szczepanski and Knight, 2014), abnormal function of the prefrontal cortex is associated with other disease such as schizophrenia (Mubarik and Tohid, 2016) and obsessive-compulsive disorder (Piras et al., 2015).
The prefrontal cortex appears to be involved in a variety of behavioral and cognitive processes. Among other things, the ventromedial prefrontal cortex is involved in problem solving (Peters et al., 2017), theory of mind (Stuss et al., 2001), attention, goal-directed behavior, working memory (Carlen, 2017), executive function (Yuan and Raz, 2014), cognitive flexibility, motivation, social cognition (Szczepanski and Knight, 2014), and cognitive control (Higo et al., 2011). Furthermore, the results from a meta-analysis found a positive association between prefrontal thickness and volume and executive function (Yuan and Raz, 2014).
In addition to its association with neurodegeneration and neuropsychiatric disease, the prefrontal cortex appears vulnerable to environmental insult, such as traumatic brain injury (Stuss, 2011) and long-term cannabis use (Lundqvist et al., 2001), and it is clear that lesions to the prefrontal cortex can result in changes in behavior and cognitive function (Szczepanski and Knight, 2014).
Air pollution appears to be associated with declines in cognitive function and possibly dementia (Power et al., 2016). Similarly, emerging evidence suggests that exposure to air pollution, specifically nitrogen dioxide and nitrogen oxides, is associated with symptoms of psychosis in adolescents (Newbury et al., 2019). In addition, both fine particulate matter (diameter ≤2.5 μm; PM2.5) and nitrogen dioxide have been associated with risk for suicide (Bakian et al., 2015). As such, the effects of air pollution could potentially involve multiple brain regions as evidenced by associations with both behavior and cognition as well as strong evidence that air pollution affects the central nervous system (Babadjouni et al., 2017). Exposure to air pollution plausibly could affect the brain via several mechanisms, including neurotoxicity from inflammation and oxidative stress (Costa et al., 2017). In children, there is an association between exposure to high concentrations of air pollution and evidence of damage to the prefrontal cortex (Calderon-Garciduenas et al., 2016), and pollution also has been associated with changes in the prefrontal cortex in older adults (Casanova et al., 2016; Power et al., 2018).
Based on the overarching importance of prefrontal cortex function and the involvement of the prefrontal cortex in some types of neurodegeneration and given the associations between prefrontal-cortex dysfunction and environmental factors including toxins found in air pollution, we sought to investigate further associations between an array of toxins in air pollution and gray-matter volume of several regions in the prefrontal cortex using the large, community-based adult UK Biobank (http://www.ukbiobank.ac.uk) dataset while adjusting for potentially confounding demographic and medical variables.
Section snippets
Study sample
Study participants came from the UK Biobank, a community-based sample of approximately 500,000 adults enrolled at approximately ages 40–69 years between 2006 and 2010 and sampled using population-based registries (http://www.ukbiobank.ac.uk). The UK Biobank assessed participants at 22 centers (Sudlow et al., 2015). The Research Ethics Committee (reference 11/NW/0382) gave ethical approval, and all subjects provided informed consent (http://biobank.ctsu.ox.ac.uk/crystal/field/cgi?id=200). The UK
Results
The final sample comprised of UK Biobank participants who had MRI data and non-missing values for the covariates was 18,288. Fifty-two percent of the sample were women. The average age was 62.15 years, with a range from 44 to 80 years. Fifty percent of the sample had a college degree, and 97 percent were white. The average PM2.5 concentration was 9.90 μg/m3, with a standard deviation of 1.01 and a range from 8.17 μg/m3 to 19.65 μg/m3. Table 1 lists means, standard deviations (for continuous
Discussion
The main finding from this community-based dataset of 18,288 participants is that PM2.5, PM10, and nitrogen oxides concentrations are associated with decreased volume of the prefrontal cortex in models adjusted for several variables that could potentially confound this association. In this dataset, the frontal poles appeared to be particularly sensitive to the effects of air pollution, suggesting that individual prefrontal regions might differ in their vulnerability to air pollution. Further,
Acknowledgements
This research has been conducted using the UK Biobank Resource under Application Number 41535. We also acknowledge the participants in the UK Biobank.
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