Effects of Air Pollution on Neurodegeneration: Implications for Physiotherapy

Original Editors - Srishti Banerjee User Name

Top Contributors - Kim Jackson, Lucinda hampton and Srishti Banerjee      

Introduction[edit | edit source]

The World Health Organization defines air pollution as the contamination of the indoor or outdoor environment by a chemical, physical or biological agent that modifies the natural characteristics of the environment[1] . Air pollution has become a major challenge faced by most countries across the globe. According to a WHO report, ambient air pollution accounts for about 4.2 million deaths per year due to stroke and lung cancer, as well as acute and chronic lung disease. In addition to outdoor air pollution, indoor air pollutants such as smoke from cooking fires in low and middle-income countries account for about 3.8 million premature deaths.

The air pollution index (which is the measurement of air pollution) provides information about the detrimental effects of air pollution. The air pollution index of about 1oo signifies the moderate quality of air. However the index remains as high as  200 in countries like India and China which signifies moderately polluted air ,potent enough to cause breathing difficulties in patients with heart and lung diseases. Diesel exhaust is considered one of the largest contributors to such poor air quality in India and China. In Mega Cities such as Delhi, diesel exhaust contributes to about 72 % of air pollution.

Air pollution has a detrimental effect on health, and the ill effects are extensively studied specifically in the cardiorespiratory system ( ie the Heart and Respiratory System). However, in the past 15 years, there is emerging evidence of the detrimental effects of air pollution on the nervous system. We as physical therapists, on a regular clinical basis, deal with a lot of patients with neurological deficits therefore it is important to consider air pollution as an emerging cause of neurological deficits.

Air pollution comprises a mixture of particulate matter and gases. Ground-level ozone, carbon monoxide, sulfur oxides, and nitrogen oxides comprise the gaseous part of air pollution, while the particulate matter is comprised of organic compounds such as polycyclic aromatic hydrocarbons, endotoxins, and metals such as vanadium, nickel, and manganese (see also Heavy Metal Toxicity) [2]. The particulate matter, a mixture of solid particles and liquid droplets being suspended in the air, has a potent effect on the nervous system. These ambient particles exist in various sizes and aerodynamic properties, being defined as:

  1. Coarse particulate matter with a diameter of 2.5 to 10µm (PM10): are respirable and emitted from road and agriculture dust, tire wear emission, wood combustion, mines, construction and demolition works.
  2. Fine particulate matter with a diameter of less than 2.5µm (PM2.5): is formed by condensation of vapors formed as a result of combustion and industrial activities emitted from oil refineries, residential fuel combustion, power plants, and wildfires.
  3. Ultrafine particulate matter(UFPM) of less than 0.1 µm diameter: specifically emitted from vehicles, aircraft, and submarines. Are the most potent for the pathologically induced changes due to their size which makes for easy lung deposition, penetration, and have extended effects beyond the central nervous system(CNS).

PM2.5 and UFPM have potent effects on the central nervous system (apart from being toxic to cardiorespiratory following inhalation) they can cross the blood air barrier (alveolar-capillary barrier) and reach the peripheral circulation and brain [3].

Impact of air pollution on the brain[edit | edit source]

Air pollution and neurodevelopment[edit | edit source]

The infant’s brain is particularly vulnerable to the potent indoor and outdoor pollutants because of the easy absorption of the toxins, which easily gains access to the developing brain and the infant’s brain being unable to detoxify these toxins [4]. The clinical manifestations, such as impaired neurocognitive function and behavioral changes in infants, are associated with alteration of critical processes in the brain (for example synaptogenesis i.e. development of cell to cell communication due to pollutant exposure) [5]. The major source of indoor ambient air pollution is cooking gas and gas cookers, commonly present in households in developed countries. A complex mixture of volatile compounds, sulfur dioxide, particulate matter less than PM10 and UFPM, carbon dioxide, nitric acid, carbon monoxide, and nitrogen dioxide are produced by cooking gas[6] ,[7].

As women and young children tend to spend a greater amount of time indoors and specifically in the kitchen, they are greatly affected by these indoor pollutants rather than outdoor pollutants. These indoor pollutants have a potent effect on the fetal as well as young brain as the maturation of the brain cortex is intensive in the initial years of life. There is emerging evidence of the potent effect of air pollution on the fetal brain, which is suggestive of intrauterine growth retardation, low and very low birth weight, and prematurity[8]. See also Neonatal Intensive Care Unit

This is associated with maternal exposure to pollutants in the second and third trimesters of pregnancy.

  • Studies by Alehan et al:  Maternal exposure to non-lethal CO, due to defective indoor gas heater led to postnatal abnormalities such as dystonia in the infant at 2 months of age. In addition to this, the changes seen on brain MRI were abnormal signal changes in globus pallidus and basal ganglia during the first few years of life. The child showed gross motor growth retardation, spasticity, severe dystonia, and mild mental retardation[9].
  • Study by Vrijheid et al.: 2012 found a decline in cognitive development during the first 14 months of life in exposed infants[10] .
  • In the past few years, several studies have found an association between exposure to outdoor pollutants, generated specifically from vehicular emissions, and autism[11] [12],[13]

Air pollution and neurodegeneration[edit | edit source]

Alzheimer’s disease (AD) and Parkinson’s disease are neurodegenerative diseases found to be associated with air pollution exposure [14]. Studies have shown the presence of CD-68, CD-163, HLA-DR positive cells which are indicative of infiltrating monocytes or activation of microglia, elevated pro-inflammatory markers such as interleukins, cyclooxygenase -2, increased Aβ2ease i.e. is a hallmark sign for Alzheimer’s, damage to the blood-brain barrier and activation of endothelial cells. It is interesting to note that these changes are specific to the frontal cortex, substantia nigra, and vagus nerve[15]. Exposure to air pollution leads to deposition of Aβ42  i.e. beta-amyloid which is a part of plaques and α-synuclein which is a part of the Lewy body in the early year of life which is indicative of premature aging of the brain[16]. One of the underlying mechanisms associated with this is the nanoparticles and corresponding oxidative stress from the pollution results in modification of aggregation and rate of protein fibrillation which in turn affects Aβ and α-synuclein[17] [1][2]. A study conducted by Jung et al established a strong association between long-term exposure to O3 and PM2.5 increased the risk of developing AD by 138% in the age group older than 65 years for every 4.34µg/m3 in PM2.5  over 10 years of follow up [3].

Air pollution and stroke[4][edit | edit source]

Acute as well as chronic exposure to air pollution is established as a predisposing factor to the occurrence of stroke. The potential underlying mechanisms can be divided into two categories 1. Following acute exposure 2. Following chronic exposure.

Acute exposure to air pollution has transient effects such as rupture of a plaque or formation of thrombus which leads to an ischaemic stroke. In addition to this hemorrhagic stroke results due to rupture of an aneurysm or microaneurysm. Acute exposure to air pollution results in a transient increase in blood coagulability or blood pressure precipitating a stroke. Spikes in air pollution occurring on daily basis are a trigger of these acute effects.

Chronic exposure to air pollution is described as sustained exposure to high levels of pollutants for a prolonged duration of time such as months and years. Chronic exposure to air pollution leads to a progression of the atherosclerotic process which was triggered due to acute exposure to air pollution.

Air Pollution and Other Miscellaneous Neurological Disorders[edit | edit source]

It has been established that air pollutants results in low circulating vitamin D levels. There is an inverse relationship between serum vitamin D levels and the risk of multiple sclerosis.   Therefore air pollution tends to increase the risk of developing multiple sclerosis. In addition to this air pollution is found associated with neurological disorders such as depression, schizophrenia, and attention deficit hyperactivity disorder however, a clear-cut establishment of a link with air pollution is still under research.[5][6]

Implications for PTs[edit | edit source]

It is important to take into consideration the deleterious effects of air pollution as a physiotherapist because it is important for a physical therapist to have detailed documentation of environmental history at home and work to know the exposure of the individual to air pollution. It is important to consider air pollution in cases of difficult diagnostic where all the other causative etiologies are ruled out. This is even applicable in the case of infants with developmental disorders where other etiological factors are ruled out and:

  • If the mother was exposed to air pollution during pregnancy or
  • If after birth the neonate and mother are chronically exposed to air pollution

However, this is a proposed hypothesis and further research is required for validation.

References [edit | edit source]

  1. 1.0 1.1 1.     Air Pollution in India: Major Issues and Challenges. (n.d.). Www.teriin.org. https://www.teriin.org/article/air-pollution-india-major-issues-and-challenges
  2. 2.0 2.1  Akimoto, H. (2003). Global Air Quality and Pollution. Science, 302(5651), 1716–1719. https://doi.org/10.1126/science.1092666
  3. 3.0 3.1 Craig, L., Brook, J. R., Chiotti, Q., Croes, B., Gower, S., Hedley, A., Krewski, D., Krupnick, A., Krzyzanowski, M., Moran, M. D., Pennell, W., Samet, J. M., Schneider, J., Shortreed, J., & Williams, M. (2008). Air Pollution and Public Health: A Guidance Document for Risk Managers. Journal of Toxicology and Environmental Health, Part A, 71(9-10), 588–698. https://doi.org/10.1080/15287390801997732
  4. 4.0 4.1 Grandjean, P., & Landrigan, P. (2006). Developmental neurotoxicity of industrial chemicals. The Lancet, 368(9553), 2167–2178. https://doi.org/10.1016/s0140-6736(06)69665-7
  5. 5.0 5.1 Rice, D., & Barone, S. (2000). Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environmental Health Perspectives, 108(suppl 3), 511–533. https://doi.org/10.1289/ehp.00108s3511
  6. 6.0 6.1 Ng, T. P., Seet, C. S. R., Tan, W. C., & Foo, S. C. (2001). Nitrogen dioxide exposure from domestic gas cooking and airway response in asthmatic women. Thorax, 56(8), 596–601. https://doi.org/10.1136/thx.56.8.596
  7. Ng, T. P., Seet, C. S. R., Tan, W. C., & Foo, S. C. (2001). Nitrogen dioxide exposure from domestic gas cooking and airway response in asthmatic women. Thorax, 56(8), 596–601. https://doi.org/10.1136/thx.56.8.596
  8. Dennekamp, M. (2001). Ultrafine particles and nitrogen oxides generated by gas and electric cooking. Occupational and Environmental Medicine, 58(8), 511–516. https://doi.org/10.1136/oem.58.8.511
  9. Alehan, F., Erol, I., & Onay, Ö. S. (2007). Cerebral palsy due to nonlethal maternal carbon monoxide intoxication. Birth Defects Research Part A: Clinical and Molecular Teratology, 79(8), 614–616. https://doi.org/10.1002/bdra.20379
  10. Vrijheid, M., Martinez, D., Aguilera, I., Bustamante, M., Ballester, F., Estarlich, M., Fernandez-Somoano, A., Guxens, M., Lertxundi, N., Martinez, M. D., Tardon, A., & Sunyer, J. (2012). Indoor Air Pollution From Gas Cooking and Infant Neurodevelopment. Epidemiology, 23(1), 23–32. https://doi.org/10.1097/ede.0b013e31823a4023
  11. Becerra, T. A., Wilhelm, M., Olsen, J., Cockburn, M., & Ritz, B. (2013). Ambient Air Pollution and Autism in Los Angeles County, California. Environmental Health Perspectives, 121(3), 380–386. https://doi.org/10.1289/ehp.1205827
  12. Roberts, A. L., Lyall, K., Hart, J. E., Laden, F., Just, A. C., Bobb, J. F., Koenen, K. C., Ascherio, A., & Weisskopf, M. G. (2013). Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants. Environmental Health Perspectives, 121(8), 978–984. https://doi.org/10.1289/ehp.1206187
  13. Volk, H. E., Hertz-Picciotto, I., Delwiche, L., Lurmann, F., & McConnell, R. (2011). Residential Proximity to Freeways and Autism in the CHARGE Study. Environmental Health Perspectives, 119(6), 873–877. https://doi.org/10.1289/ehp.1002835
  14. Hirtz, D., Thurman, D. J., Gwinn-Hardy, K., Mohamed, M., Chaudhuri, A. R., & Zalutsky, R. (2007). How common are the “common” neurologic disorders?. Neurology, 68(5), 326–337. https://doi.org/10.1212/01.wnl.0000252807.38124.a3
  15. Calderón-Garcidueñas, L., Solt, A. C., Henríquez-Roldán, C., Torres-Jardón, R., Nuse, B., Herritt, L., Villarreal-Calderón, R., Osnaya, N., Stone, I., García, R., Brooks, D. M., González-Maciel, A., Reynoso-Robles, R., Delgado-Chávez, R., & Reed, W. (2008). Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults. Toxicologic Pathology, 36(2), 289–310. https://doi.org/10.1177/0192623307313011
  16. Kim, H., Kim, W.-H., Kim, Y.-Y., & Park, H.-Y. (2020). Air Pollution and Central Nervous System Disease: A Review of the Impact of Fine Particulate Matter on Neurological Disorders. Frontiers in Public Health, 8.
  17. Colvin, V. L., & Kulinowski, K. M. (2007). Nanoparticles as catalysts for protein fibrillation. Proceedings of the National Academy of Sciences, 104(21), 8679–8680. https://doi.org/10.1073/pnas.0703194104