Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly

Abstract

Animal studies have suggested that fine particulate matter (PM) can translocate from the upper respiratory tract to the brain and cause brain inflammation. Brain inflammation is involved in the pathogenesis of neurodegenerative diseases. Hypothesizing therefore that long-term exposure to fine PM might contribute to the development of Alzheimer's disease (AD), the objective of this study was to investigate the association between exposure to fine PM and mild cognitive impairment (MCI) which is associated with a high risk of progression to AD. A study group of 399 women aged 68–79 years who lived for more than 20 years at the same residential address has been assessed for long-term exposure to PM and tested for MCI. The exposure assessment comprised background concentration of PM₁₀ and traffic-related PM indicated by the distance of the residential address to the next busy road. The women were assessed for MCI by a battery of several neuropsychological tests and their odor identification ability. Consistent effects of traffic-related air pollution exposure on test performances including a dose–response relation were found. The associations were adjusted for potential confounders using regression analysis. These results indicate that chronic exposure to traffic-related PM may be involved in the pathogenesis of AD.

Introduction

High levels of air pollution are associated with chronic respiratory and cardiovascular health effects including a decline in lung function (Brunekreef and Holgate, 2002; Schikowski et al., 2005), an increase in blood plasma viscosity (Peters et al., 1997), a reduction of heart rate variability (Gold et al., 2000; Schwartz et al., 2005) and multiple signs of inflammation (Sun et al., 2005; Calderon-Garciduenas et al., 2007). These detrimental effects are thought to be caused by fine particulate matter (PM) in ambient air, of which traffic is a major source. Recent studies suggest that exposure to PM may be linked to brain damage by chronic inflammatory processes as well. Accordingly, animal studies indicate that particles can translocate from the upper respiratory tract to the central nervous system and the brain (Oberdorster et al., 2004; Elder et al., 2006). In an observational study with canines, an association of chronic exposure to high levels of air pollutants with signs of chronic brain inflammation, such as nuclear factor-κB activation and inducible nitric oxide synthase production, could be demonstrated for the first time (Calderon-Garciduenas et al., 2002). Similarly, in mice that were exposed to PM, brain tissues showed higher levels of pro-inflammatory cytokines and chemokines (Campbell et al., 2005). A single administration of nanoparticles in the mouse olfactory bulb results in changes in neurotransmitter levels and pro-inflammatory cytokine mRNA expressions (Tin-Tin-Win-Shwe et al., 2008). In a study using autopsy brain samples, significantly higher cyclooxygenase-2 expression, an inflammation mediator, in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were observed in subjects with lifelong severe air pollution exposure compared to those with low exposure (Calderon-Garciduenas et al., 2004). In a similar study with healthy children and young adults who died suddenly, early signs of effects of lifelong exposure to high concentrations of air pollutants were an upregulation of mRNA COX2, IL-1beta, and the innate immunity receptor DC14 in several regions of the brain as well as frontal disruption of the blood–brain barrier and evidence of an activated inflamed cerebral endothelium (Calderon-Garciduenas et al., 2008).

Four pathways, at least, through which long-term exposure to PM induces neuroinflammation and neurodegeneration are now being discussed (Calderon-Garciduenas et al., 2008). First, the induction of chronic respiratory and systemic inflammation by PM produce pro-inflammatory cytokines which in turn affect the blood–brain barrier, involve neural–immune interactions and lead to chronic oxidative stress. Second, the olfactory pathway offers a direct access to the olfactory bulb since olfactory neurons have been seen loaded with PM in children. Third, PM-associated lipopolysaccharides are likely to play an important role in the vagus/trigeminal pathways if PM enters the respiratory and digestive systems. Finally, ultrafine PM directly produces reactive oxygen species, in consequence, damage the blood–brain barrier and enhance the Abeta42 production. Brain inflammation and the accumulation of Abeta42 has been implicated in the disease process of neurodegenerative diseases including Alzheimer's disease (Tuppo and Arias, 2005; McGeer and McGeer, 2007).

The incidence of Alzheimer's disease is constantly increasing (Ferri et al., 2005) mainly because of an aging population, but environmental factors may have pathogenetic influence on the development of neurodegenerative diseases additionally. Mild cognitive impairment (MCI) is associated with a high risk of progression to Alzheimer's disease. It is defined as cognitive decline greater than expected for an individual's age and educational level but that does not interfere notably with activities of daily life (Gauthier et al., 2006). While some individuals with MCI remain stable or return to baseline levels over time, more than 50% progress to dementia within 5 years (Gauthier et al., 2006). Hence, MCI could be considered a prodromal stage for Alzheimer's disease and less frequent forms of dementia.

In the present study we investigated whether long-term exposure to traffic-related fine PM is linked to the development of cognitive impairment. In order to address this question we determined MCI by means of neuropsychological tests in a cohort of elderly women, whose exposure to PM was assessed by background concentrations and distance of the residential address to the next busy road.