The emerging risk of exposure to air pollution on cognitive decline and Alzheimer's disease - Evidence from epidemiological and animal studies

Abstract

As incidence of Alzheimer's disease (AD) and other neurodegenerative diseases rise, there is increasing interest in environmental factors which may contribute to disease onset and progression. Air pollution has been known as a major health hazard for decades. While its effects on cardiopulmonary morbidity and mortality have been extensively studied, growing evidence has emerged that exposure to polluted air is associated with impaired cognitive functions at all ages and increased risk of AD and other dementias in later life; this association is particularly notable with traffic related pollutants such as nitrogen dioxide, nitrous oxide, black carbon, and small diameter airborne solids and liquids known as particulate matter. The exact mechanisms by which air pollutants mediate neurotoxicity in the central nervous system (CNS) and lead to cognitive decline and AD remain largely unknown. Studies using animal and cell culture models indicate that amyloid-beta processing, anti-oxidant defense, and inflammation are altered following the exposure to constituents of polluted air. In this review, we summarize recent evidence supporting exposure to air pollution as a risk for cognitive decline at all ages and AD at later lifetime. Additionally, we review the current body of work investigating the molecular mechanisms by which air pollutants mediate damage in the CNS. Understanding of the neurotoxic effects of air pollution and its constituents is still limited, and further studies will be essential to better understand the cellular and molecular mechanisms linking air pollution and cognitive decline.

Keywords: Cognition; Dementia; Particulate matter.

Fig. 1

A depiction of particulate matter (PM) primary deposition areas in the body and potential routes to affect the CNS. Larger particles (PM₁₀, orange) tend to be trapped in the upper respiratory tract, while the fine (PM_2.5, green) and ultra-fine (PM_0.1, blue) fractions can reach deep in the lungs . Ultra-fine PM deposit in the alveoli and can cross into the interstitium and blood, where they may cause systemic effects , . In addition, ultra-fine PM can directly cross the olfactory epithelium and enter the CNS , .

Fig. 2

Proposed pathways by which particulate matter exposure leads to neurotoxicity and cognitive deficits. Direct infiltration of PM to the brain , can provide a pathway for metals and other neurotoxic chemicals to accumulate in neural tissue, and potentially provide a reactive surface as occurs in the lungs . Systemic effects from PM infiltrating the blood via the alveoli include cardiovascular disease , , which can lead to impaired cognition and promote AD pathology . Both pathways potentially contribute to the inflammatory, glial, and amyloid pathology responses observed in animal models , , , cell culture , , , and human studies , , . The cascade from these responses to neurotoxicity and cognitive loss is well documented , , , and consistent with results showing neuronal toxicity , , and behavioral effects , , observed with PM exposure.