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Air Pollution, Growing brAin and cognitive disordeR in children

Periodic Reporting for period 1 - APGAR (Air Pollution, Growing brAin and cognitive disordeR in children)

Reporting period: 2015-10-15 to 2017-10-14

Brain maturation during the first years of life is very intensive. This period of life is considered an important window for brain development, but is also particularly vulnerable to environmental insults that may interfere with the cascade of neurodevelopmental processes . Traffic-related air pollution, a global public health threat, may be one of these neurodevelopment disruptors. All around the world, air pollution exposure has indeed been associated with adverse effects on mental development and on behavioral functions such as attention, with a reduced global IQ, with a decrease in memory and academic performance, and with a higher prevalence of Attention Deficit Hyperactivity Disorder (ADHD) and autism. However, studies about the potential damages on growing brain induced by chronic exposure to air pollution are still scarce. Interfacing environmental epidemiology and neuroimaging may offer the opportunity to yield insights on mechanisms underlying the association between exposure to air pollution and cognitive disorder by detecting which brain function and structures may be altered by air pollution exposure.
The objectives of the APGAR project were: 1) To determine the impact of urban air pollution on the structures and functions of the growing brain in children from the general population, 2) To determine to what extent the urban air pollution-related structural and functional changes of the growing brain are associated with cognitive performance in children.
279 primary schoolchildren aged 8-12 years from the BREATHE Study underwent brain neuroimaging between 2012 and 2013 in Barcelona, Spain. Several aspects of their cognition and their behavior were evaluated: ADHD symptoms using the ADHD-DSM-IV scale, general behavior using the Strengths and Difficulties Questionnaire, attention using the Attention Network Test, working and superior working memory using the n-back test. Air pollution levels were measured at the children´s school at the time of the study, and estimated at the residential address of each participant during the prenatal period.
We performed statistical analyses to examine the relationships between 1) brain structures volumes and air pollution levels, 2) brain structures volumes and cognition and behavior, 3) air pollution levels and cognition.
Firstly, we found that an increase in polycyclic aromatic hydrocarbons (PAHs) levels , and in particular an increase of 70 pg/m3 in outdoor benzo[a]pyrene (BAP) levels in the school environment, was associated with a reduction corresponding to almost 2% of the mean caudate nucleus volume (when the mean caudate nucleus volume is only 7 to 8% approximately smaller in children with ADHD). It is important to highlight that the levels of BAP in the different schools of the study ranged between 20 and 304 pg/m3 (median of 86 pg/m3), levels far below the legislated annual target levels of 1000 pg/m3 for BAP established in the European Union (European Council Directive 2004/107/EC,
Secondly, we observed that an increase of approximately 7µg/m3 in the concentration of fine particles (particles matter with aerodynamic diameter <2.5µm, PM2.5) during the third trimester of pregnancy was significantly associated with a reduction corresponding to almost 4% of the mean volume of the corpus callosum (when the mean corpus callosum volume is only 16% approximately smaller in children with autism), and with an increase corresponding to almost 13% of the mean lateral ventricles volume. These prenatal PM2.5 levels ranged between 12.7 and 45.0 µg/m3 (median of 23.6 µg/m3), when the limit target value established by the European Union for 2015 was 25 µg/m3 (European Council directive 2008/50/EC,
These relationships between air pollution exposure and brain structural changes were observed independently of children´s age, sex, intracranial volume, maternal education and residential neighborhood socioeconomic status.
The BAP-related caudate nucleus change appeared to be subclinical given that we only observed a trend for an association between a reduction in the caudate nucleus volume and an increase in ADHD symptoms, but the relationship was not statistically significant.
In contrast, the reduction in the corpus callosum and the increase in the lateral ventricles volumes were significantly associated with an increase in behavioral problems (higher hyperactivity subscore on the ADHD scale and higher total score on the Strengths and Difficulties Questionnaire).
So far, the few previous studies interfacing neuroimaging and environmental epidemiology in children had shown that chronic exposure to air pollution may have a deleterious impact on cerebral white matter. However, these studies had some limitations such as very small size samples, sample coming from minority population limiting the generalization of the results or aggregated estimations of air pollution exposure levels.
In conclusion, in our large sample of children from the general population and with real measures of PAHs levels at schools as well as with personal estimations of prenatal exposure to PM2.5 the results from the APGAR project suggest that urban air pollution has also an impact on subcortical brain structures involved in many crucial cognitive and behavior processes. The air pollution-related brain changes identified were observed for levels of air pollution exposure below, or at least not exceeding, the target levels established by the European Union. Hence, by providing scientific arguments about the deleterious effects of urban air pollution on the brain of children encountering air pollution level in the range of this recommended by the Europe legislation, our project´s results may lead to decisive actions to improve air quality in Europe.
Understanding the link between air pollution and cognition: the central role of neuroimaging