Even 'Safe' Levels of Air Pollution Tied to Brain Shrinkage

Batya Swift Yasgur, MA, LSW

November 23, 2020

Areas where there are high levels of fine-particle air pollution may increase Alzheimer's-like brain shrinkage, new research suggests.

Results of a large longitudinal study show that women who lived in areas in which there were microscopic particulate matter with aerodynamic diameters <2.5 μg (PM2.5) per cubic meter of air had a significantly increased risk for brain shrinkage on imaging.

Researchers studied more than 700 women (mean age, 78 years) who were free of dementia at baseline. Participants underwent MRI at baseline and again 5 years later.

Each 3-μm increase in air pollution exposure was associated with an increase of .03 points in brain shrinkage scores at the end of the 5-year period. These scores were in turn associated with a 24% increased risk for Alzheimer's disease (AD).

"Our findings add to the literature showing that air pollution may increase risk of Alzheimer's disease," lead author Diana Younan, PhD, MPH, senior research associate, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, told Medscape Medical News.

"However, air pollution is a modifiable risk factor, and even those living in areas with high air pollution can make concerted efforts to reduce their exposure to these pollutants, for example, monitor air quality daily, stay indoors on days when air pollution is especially high, and keep car vents closed when driving," she said.

The study was published online November 18 in Neurology.

Longitudinal Approach

"Compelling evidence has demonstrated that ambient pollution" — especially particulate matter of PM2.5 — "is an environmental risk factor for brain aging" and is associated with an increased risk for dementia and AD, but the underlying mechanism of this association is not clear, the authors write.

"We wanted to see whether these fine particles may alter brain structure, since small brain volumes are a risk factor for dementia and Alzheimer's disease," said Younan.

She noted that this study differs from previous studies because "we used a longitudinal approach using two brain scans, while others only had brain scans at one time point."

The researchers studied data from participants (n = 1365; mean age, 77.9 ± 3.7 years) in the Women's Health Initiative Magnetic Resonance Imaging Study (WHIMS-MRI), which focused on community-dwelling older women who had undergone brain MRI between April 2005 and January 2006. Of these participants, 730 underwent a second scan during the period 2010–2013. The average amount of time between scans was 4.77 years.

The researchers used participants' addresses, together with air monitoring data, to create a spatiotemporal model that estimated the 3-year average exposure to PM2.5 prior to the first MRI.

Additional data included information on demographics, education, socioeconomic, lifestyle factors, and clinical characteristics.

New Brain Shrinkage Measure

Younan explained that unlike previous studies, this study used a "different way of measuring brain shrinkage" by scoring participants' brain scans on the basis of their similarity to AD patterns "using a machine learning tool that had been 'trained' to learn these patterns via brain scans of people with Alzheimer's disease."

The MRI data captured high-dimensional gray matter atrophy in brain regions identified in previous research as vulnerable to AD. These areas included the amygdala, the hippocampus, the parahippocampal gyrus, the thalamus, the inferior temporal lobe areas, and the midbrain.

The researchers used linear models to explore the association between PM2.5 and AD pattern similarity (AD-PS) scores after accounting for potential confounders as well as white matter lesion volumes.

The primary study outcome was the 5-year standardized change in AD-PS scores from MRI-1 to MRI-2. Scores ranged from 0 – 1. Higher scores were associated with greater neuroanatomic AD risk.

Participants were divided into quartiles on the basis of their average exposures to air pollution during the 3 years prior to MRI-1. The lowest group was exposed to an average of 7 – 10 μg/m3; and the highest group was exposed to an average of 13 – 19 μg/m3.

"Concerning" Findings

Cross-sectional analyses found no association at baseline in participants between PM2.5 and baseline AD-PS score (β = –.004; 95% CI, –0.019 to 0.011).

However, the average AD-PS scores increased by an average of 0.17 ± 0.15 between MRI-1 and MRI-2.

Longitudinal analysis of participants who completed the full 5-year study (n = 712; aged 77.4 ± 3.5 years) showed that each interquartile range increase in PM2.5 (2.82 μg/m3) was associated with a 24% increase in AD-PS score (hazard ratio, 1.24; 95% CI, 1.14 – 1.34) at the end of the 5 years.

Racial/ethnic minorities (particularly Black or Hispanic White participants), residents of Northeastern regions, people who were unemployed at baseline, and those who had low white matter lesions were more likely to be in the upper two quartiles of PM2.5 exposure (≥10.91 μg/m3).

Even more concerning, the association was found in participants who lived in areas with PM2.5 levels below safety standards (<12 μg/m3), as determined by the US Environmental Protection Agency.

"Fine-particle pollution was associated with shrinkage in areas of the brain that are vulnerable to Alzheimer's disease, and these associations were still present at low exposure levels below the current US regulatory standards for fine particles and among healthy women without cognitive impairment or cardiovascular diseases that may accelerate brain aging," said Younan.

She noted that women are "disproportionally affected by Alzheimer's disease compared to men, and although our study only included women, other studies that included both men and women are also seeing associations between air pollution and brain shrinkage."

Clean Air Act

Commenting on the study for Medscape Medical News, Heather Snyder, PhD, vice president of medical and scientific operations, Alzheimer's Association, said data by Younan and colleagues that were reported at the 2019 Alzheimer's Association International Conference suggested that AD risk increased with increased air pollution.

"However, what is exciting [about that study] is that the research team also found that when an individual is engaged in physically and mentally stimulating activities, they may have some protection against the risk posed from outdoor air pollution exposure in late life," said Snyder, who was not involved with the current research.

"This suggests that staying active, eating a balanced diet, and staying cognitively engaged — as you are able — may be strategies to impact your later life risk," Snyder said.

Younan emphasized that "most importantly, we need to make sure we are continuing to enforce the Clean Air Act."

The study was supported by the National Institute on Aging and the Southern California Environmental Health Sciences Center. The Women's Health Initiative Programs are funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the US Department of Health and Human Services. Sources of the Women's Health Initiative Memory Study are listed on the original article. Younan and coauthors and Snyder report no relevant financial relationships.

Neurology. Published online November 18, 2020. Abstract

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