January/February 2024

Pollution and Brain Health
By Mark D. Coggins, PharmD, BCGP, FASCP
Today’s Geriatric Medicine
Vol. 17 No. 1 P. 18

Among the many ways it damages the body, pollution affects cognition.

Air pollution is a global threat to the health of every person, with the World Health Organization reporting that 99% of the world’s population is exposed to dangerous levels of air pollution.1 It causes approximately nine million deaths annually and accounts for one in six deaths worldwide.2 While air pollution is harmful to the lungs and airway, it can also damage most organs in the body, leading to a range of diseases, including worsening asthma and lower respiratory infections, COPD, cardiovascular disease, stroke, cancers, systemic inflammatory diseases, diabetes, osteoporosis and bone fractures, and many others.3 There’s also growing evidence raising concern about the effects of air pollution on the central nervous system, including decreased cognitive functions and the increased risk of dementia and mental health issues.

What Is Air Pollution?
Air pollution is contamination of the indoor or outdoor environment by any chemical, physical, or biological agent that modifies the natural characteristics of the atmosphere.1 It’s made up of mixtures of different compounds, including particulate matter (PM), carbon monoxide, lead, ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide.4 Common sources of air pollution include household combustion devices, motor vehicles, industrial facilities, and forest fires.

Particulate Matter
PM, also known as particle pollution, is a term used to describe a mixture of tiny solid particles and liquid droplets suspended in air. PM comprises various components, including nitrates, sulfates, organic chemicals, metals, and particles from the soil, dust, and allergens (pollen or mold spores). Particle pollution mainly comes from motor vehicles, woodburning heaters, and industry; however, it can also come from natural events such as bushfires or dust storms.

Categories of PM
PM is separated into three categories based on physical size: coarse particles (PM10), fine particles (PM2.5), and ultrafine particles (PM0.1). These sizes generally differ in origin and severity of health effects.

Coarse Particles (PM10)
PM10 describes coarse particles with a diameter of 10 μm or smaller. These can irritate the nose, throat, and eyes and are small enough to pass through to the lungs, causing severe health effects to the heart and lungs. PM10 consists primarily of insoluble crust-derived minerals, biological material (such as pollen, endotoxins, fungi, and bacteria), and sea salts.5 Also, they’re commonly created directly through construction work, road dust, or natural dust storms.

Fine Particles (PM2.5)
PM2.5 describes fine particles with a diameter of 2.5 μm or smaller. For perspective, a single human hair is almost 30 times larger than the largest fine particle.6 Their small size makes these particles extremely dangerous, as they can find their way from the lungs into the bloodstream. PM2.5 particles can originate from natural or human-made sources and come primarily from the combustion of gasoline, oil, diesel fuel, or wood.

Ultrafine Particles (PM0.1)
PM0.1 describes ultrafine particles as those with a diameter of 0.1 μm or smaller. PM0.1 originates from similar sources as PM2.5 particles. They also represent more than 80% of the airborne PM indoors.7 Due to their small size, these particles can enter the body even more readily than larger particles and likely have the potential to cause even more significant cardiovascular toxicity and oxidative stress.

How Air Pollution Damages the Brain
Inflammation is likely behind many of the adverse health effects of air pollution. While the initial phase of inflammation is a protective mechanism in response to harmful stimuli, an inflammation cascade can occur, leading to oxidative stress throughout the body, which can cause damage and death to neurons in the brain. Air pollution can affect the brain through several potential pathways. One possibility is that pollution breathed into the lungs enters the bloodstream, setting off neuroinflammatory responses that change the permeability of the blood-brain barrier, allowing the toxic chemicals to reach and damage the brain. Another possibility is that harmful particles are inhaled into the nose and enter olfactory neurons that connect the nose to the brain, damaging neurons. Air pollution particles can also enter the stomach, causing systemic inflammation and indirect neurological damage.

Effects of Air Pollution Across the Lifespan
Air pollution’s detrimental health effects can span every stage of life, including before and during pregnancy, childhood, and adulthood. By the time an individual becomes an older adult, a great deal of damage may already have been done in the following ways.

Reproductive Outcomes
Studies have shown that air pollution negatively affects reproductive outcomes in females and males. Air pollution can affect fertility by lowering sperm count and motility. It also can impair fetal development in the womb, increasing the risk of miscarriage, premature birth, and low birth weight. Research finding that air pollution particles can travel through pregnant women’s lungs and lodge in the placenta is of great concern.8,9 More recently, researchers found that black carbon nanoparticles, a component of PM pollution, get into the first- and second-trimester placenta and reach into the organs of the developing fetus, including the lung, liver, and brain.10

Brain Development
The developing human brain is especially vulnerable to toxic chemical exposure in utero, during infancy, and early childhood. Because the brain develops during fetal life, air pollution in utero can cause permanent brain damage or increase the risk of cognitive impairment in old age.11 Further, exposure to high levels of ambient air pollution during pregnancy can lead to a more significant adverse effect on brain development than exposure during childhood.12 Prenatal PM exposure also negatively influences brain volumes, with studies demonstrating the neurological basis of impaired cognition in children exposed prenatally to air pollutants.13 Prenatal air pollution may also interfere with fetal neurodevelopment by inducing oxidative stress and inflammation or altering the placenta’s or fetus’s epigenetic programming.14

Childhood Behavioral, Cognitive, and Mental Health Concerns
High pollution levels have been found to be a risk factor for many cognitive, behavioral, and mental disorders in children.

Impact of Traffic-Related Air Pollution
Traffic-related air pollution (TRAP) is a significant concern worldwide and is associated with adverse effects on mental development and behavioral functions in children, such as attention, reduced global IQ, a decrease in memory and academic performance, and a higher prevalence of autistic spectrum disorder and ADHD.15

Autism
Autistic spectrum disorder is a neurodevelopmental condition with core characteristics involving deficits in communication skills, problems with social interactions, repetitive behaviors, and restricted interests. Exposure to TRAP, NO2, PM2.5, and PM10 during pregnancy and the first year of life has been found to be associated with autism.16

ADHD
ADHD is a common behavioral disorder in children that frequently continues throughout adulthood and is characterized by hyperactivity, inattention, and impulsiveness symptoms. Studies have shown conflicting results regarding air pollution’s role in ADHD. However, a systematic review found that nine out of 12 epidemiological studies showed an association between PM2.5 and ADHD.17 However, the researchers advised the results be reviewed with care as they categorized five of the 12 studies as high quality and seven as good quality.

Behavioral Problems and IQ
Children exposed to NO2 and PM in utero and early life may experience impaired behavioral functioning and cognitive performance.14 One study found that children whose mothers were exposed to high levels of NO2 during pregnancy, particularly in the first and second trimesters, were more likely to develop behavioral problems. In addition, each 2 μg/m3 increase in PM at age 2 to 4 years resulted in increased total behavioral problems and reduced IQ. The associations between PM2.5 and total problem score were generally stronger in girls.

Depression and Anxiety
In another study, researchers followed children in New York City from before birth to age 6 or 7. They found that children exposed while in utero to higher levels of urban air pollutants—polycyclic aromatic hydrocarbons, which are byproducts of burning fossil fuels—were more likely to experience attention problems and symptoms of anxiety and depression.18

Cognitive Function and Dementia Risk in Adults
Many studies have demonstrated an association between air pollution and reduced cognitive function and increased dementia risk.

TRAP
TRAP not only can influence cognitive and behavioral function in childhood but also has been linked to a 3% increased risk for dementia for every 1 μg/m3 of fine PM exposure.19

Impact of PM2.5, NO2, and O3 on Dementia Risk
In a study published in 2021, researchers utilized data from the Medicare Chronic Conditions Warehouse (2000–2018) to investigate the association between long-term exposure to ambient fine PM (PM2.5), NO2, and O3 and the incidence of dementia and Alzheimer’s disease, respectively.20 They constructed two national US population cohorts of those aged 65 and older combined with high-resolution air pollution datasets. The dementia cohort included approximately 2 million incident dementia cases and 0.8 million incident Alzheimer’s disease cases. For both outcomes, they found a linear concentration-response relationship between increased PM2.5 and NO2 exposure and increased incidence of dementia and Alzheimer’s dementia. However, there was no increase related to O3 exposure.

Accelerated Cognitive Decline and Dementia Risk in Women
Significant acceleration in cognitive decline was seen in a 2012 US study of almost 20,000 women between the ages of 70 and 81 exposed to higher levels of both PM10 and PM2.5. The effect of 10 μg/m3 higher PM exposure was cognitively equivalent to aging by approximately two years.21

In another study, researchers analyzed data from 3,647 women from 48 US states who were part of the Women’s Health Initiative Memory Study.22 All women were between 65 and 79 years of age and were free of dementia at the beginning of the study. Researchers found that older women who live in places with fine PM exceeding the US Environmental Protection Agency’s standard are 81% more at risk for global cognitive decline and 92% more likely to develop dementia, including Alzheimer’s. The researchers noted that if the findings hold for the general population, air pollution may be responsible for about 21% of dementia cases.

Increased Hospitalizations for Dementia
Long-term exposure to higher concentrations of PM2.5 is also associated with increased hospitalizations for dementia. There was also a slight increase in hospitalizations for dementia in those persons living in metropolitan areas vs rural areas.23

Working Memory and Orientation
A 2014 study also demonstrated a link between air pollution and cognition. Researchers used cross-sectional data on non-Hispanic Black and white men and women aged 55 and older from the 2001/2002 Americans’ Changing Lives Study (N = 780).24 The researchers assessed cognitive function by utilizing working memory and orientation tests. They found that older adults living in areas with high levels of PM2.5 were more likely to experience cognitive problems and had error rates 1.5 times greater than those of people living in less polluted areas. A later study using the Americans’ Changing Lives Study dataset found that these associations were even stronger among older adults residing in high-stress neighborhoods with poor upkeep, a lot of trash, and deteriorating buildings.25

Indoor Pollution
There’s also a risk of cognitive issues resulting from indoor pollution. A study of older adults (mean age 63.8) in Mexico found that those who resided in households that used wood or coal as their primary cooking had poorer cognitive performance across all assessments (verbal learning, attention, orientation, and verbal fluency), apart from verbal recall.26

In another study, impaired cognitive function occurred in office settings with concentrations of PM2.5 and carbon dioxide commonly seen in indoor environments. In a one-year prospective observational longitudinal study among 302 office workers in urban commercial buildings located in six countries, researchers found that increased concentrations of PM2.5 and lower ventilation rates (measured using carbon dioxide) were associated with slower response times and reduced accuracy on a series of cognitive tests.27

Benefits of Reduced Exposure
While increased exposure to air pollution increases cognitive decline, reduction in particle matter and NO2 exposure has an inverse relationship. In a study of more than 2,200 women aged 74 to 92, reduced exposure to PM2.5 and NO2 over 10 years significantly reduced dementia risk. Living in locations with greater air quality improvement was associated with slower cognitive declines in older women, who retained the cognitive ability of women 0.9 to 1.6 years younger.28,29

The Need for Increased Awareness
While research on the association between air pollution and its effects on the brain is at an early stage, the evidence is mounting. Damage to the brain from air pollution appears to begin early, and its effects could have lifelong implications. Increased awareness of the risks to the brain is warranted as this may allow one to decrease exposure to air pollution to reduce long-term risks.

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
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29. Younan D, Wang X, Millstein J, et al. Air quality improvement and cognitive decline in community-dwelling older women in the United States: a longitudinal cohort study. PLoS Med. 2022;19(2):e1003893.