Association between exposure to air pollution and prefrontal cortical volume in adults: A cross-sectional study from the UK biobank

doi:10.1016/j.envres.2020.109365

Environmental Research

Volume 185, June 2020, 109365

https://doi.org/10.1016/j.envres.2020.109365 Get rights and content

Highlights

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Prefrontal cortex volume in adults was inversely associated with air pollution.
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Education appeared to be protective against the effects of PM_2.5, NO₂ and NO_x.
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Age and sex did not appear to interact with the effects of air pollution.

Abstract

Associated with numerous cognitive and behavioral functions and with several diseases, the prefrontal cortex is vulnerable to environmental insult. Among other factors, toxins in air pollution have been associated with damage to the prefrontal cortex in children and older adults. We used data from the UK Biobank to assess further associations between an array of toxins in air pollution and gray matter in the prefrontal cortex including the left and right frontal poles, left and right superior frontal gyri, left and right frontal medial cortex, left and right orbitofrontal cortex, and left and right frontal opercula, using multivariate models adjusted for covariates that possibly could confound the association between air pollution and volume of prefrontal gray matter. The results showed inverse associations between PM 2.5, PM 10, and nitrogen oxides and prefrontal volume in models adjusted for age, sex, education, socioeconomic status, race-ethnicity, self-rated overall health, body mass index, total brain volume, smoking status, and alcohol use frequency. Education appeared to moderate the association between air pollution and prefrontal volume. The data in these analyses came from regions whose mean PM 2.5 was near the upper limit and whose mean PM 10 was under those recommended by the World Health Organization. These findings suggest that comparatively low levels of air pollution might be associated with reduced volume of the prefrontal cortex.

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; PM_2.5) 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 PM_2.5 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 PM_2.5, 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.

References (36)

F. Alfaro-Almagro
Image processing and Quality Control for the first 10,000 brain imaging datasets from UK Biobank
Neuroimage
(2018)
R.M. Babadjouni
Clinical effects of air pollution on the central nervous system; a review
J. Clin. Neurosci.
(2017)
M. Baumgart
Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective
Alzheimers Dement
(2015)
R. Beelen
Development of NO2 and NOx land use regression models for estimating air pollution exposure in 36 study areas in Europe - the ESCAPE project
Atmos. Environ.
(2013)
L. Calderon-Garciduenas
Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease
Environ. Res.
(2016)
L.G. Costa
Neurotoxicity of traffic-related air pollution
Neurotoxicology
(2017)
J. Khan
Road traffic air and noise pollution exposure assessment - a review of tools and techniques
Sci. Total Environ.
(2018)
G. Livingston
Dementia prevention, intervention, and care
Lancet
(2017)
T. Lundqvist
Frontal lobe dysfunction in long-term cannabis users
Neurotoxicol. Teratol.
(2001)
F. Piras
Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies
Cortex
(2015)

M.C. Power

Exposure to air pollution as a potential contributor to cognitive function, cognitive decline, brain imaging, and dementia: a systematic review of epidemiologic research

Neurotoxicology

(2016)

S.M. Szczepanski et al.

Insights into human behavior from lesions to the prefrontal cortex

Neuron

(2014)

T.L. Tsai

Fine particulate matter is a potential determinant of Alzheimer's disease: a systemic review and meta-analysis

Environ. Res.

(2019)

P. Yuan et al.

Prefrontal cortex and executive functions in healthy adults: a meta-analysis of structural neuroimaging studies

Neurosci. Biobehav. Rev.

(2014)

A.V. Bakian

Acute air pollution exposure and risk of suicide completion

Am. J. Epidemiol.

(2015)

K. Balakrishnan et al.

The impact of air pollution on deaths, disease burden, and life expectancy across the states of India: the Global Burden of Disease Study 2017

Lancet Planet Health

(2019)

M. Carlen

What constitutes the prefrontal cortex?

Science

(2017)

R. Casanova

A voxel-based morphometry study reveals local brain structural alterations associated with ambient fine particles in older women

Front. Hum. Neurosci.

(2016)

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Citation Excerpt :
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Association between exposure to air pollution and prefrontal cortical volume in adults: A cross-sectional study from the UK biobank

Highlights

Abstract

Introduction

Section snippets

Study sample

Results

Discussion

Acknowledgements

Neuroimage

J. Clin. Neurosci.

Alzheimers Dement

Atmos. Environ.

Environ. Res.

Neurotoxicology

Sci. Total Environ.

Lancet

Neurotoxicol. Teratol.

Cortex

Neurotoxicology

Neuron

Environ. Res.

Neurosci. Biobehav. Rev.

Acute air pollution exposure and risk of suicide completion

Am. J. Epidemiol.

The impact of air pollution on deaths, disease burden, and life expectancy across the states of India: the Global Burden of Disease Study 2017

Lancet Planet Health

What constitutes the prefrontal cortex?

Science

A voxel-based morphometry study reveals local brain structural alterations associated with ambient fine particles in older women

Front. Hum. Neurosci.