As research continues on risk factors for dementia, exposure to airborne pollutants has continued to garner attention as a target for preventive efforts. In 2020, the Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution as one of 12 potentially modifiable risk factors that together may prevent or delay approximately 40% of dementia cases worldwide.1

The addition was based on accumulating evidence in recent years that shows support for this relationship. Multiple studies have found associations between air pollution exposure and an increased risk for dementia, while improved air quality has been linked with a lower dementia risk.2-5,7

In a 2021 national cohort studybased on Medicare data from 2000-2018, Shi et al examined records pertaining to nearly 25 million beneficiaries to determine associations between exposure to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) and the incidence of dementia and Alzheimer disease (AD).2


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For incident dementia, hazard ratios (HRs) per interquartile range (IQR) increase in the 5-year average exposure to PM2.5 (3.2 µg/m3) and NO2 (11.6 ppb) prior to diagnosis were 1.060 (95% CI, 1.054-1.066) and 1.019 (95% CI, 1.012-1.026), respectively. For incident AD, HRs per IQR increase were 1.078 (95% CI, 1.070-1.086) and 1.031 (95% CI, 1.023-1.039), respectively. These relationships were approximately linear. No increase in HRs for O3 was observed for incident dementia (HR, 0.990; 95% CI, 0.987-0.993) or incident AD (HR, 0.982; 95% CI, 0.977-0.986).2

In a 2021 cohort study of 7066 older adults in France, increasing levels of PM2.5 exposure were associated with an elevated risk for all-cause dementia, and vascular/mixed dementia over a median 10-year follow-up period. No association was noted for the other 2 pollutants examined in the study, NO2 and black carbon.3

Results of imaging studies further support these findings, including a 2021 cross-sectional study of 18,178 US adults with cognitive impairment. Greater odds of positive amyloid positron emission tomography scan results were noted in those living in areas with worse air quality, with apparent associations between higher PM2.5 levels and the presence of brain amyloid-β plaques.4

The association between PM2.5 levels and the probability of amyloid PET scan positivity “was dose-dependent and statistically significant after adjusting for demographic, lifestyle, and socioeconomic factors as well as medical comorbidities,” the researchers noted.4 No association between higher O3 exposure and amyloid PET scan positivity was observed in either time frame.

The results of these latest studies are consistent with from previous research that showed positive associations between exposure to various pollutants and the risk for dementia. In a 2019 systematic review of 13 longitudinal studies from the US and several other countries, Peters et al found that higher levels of exposure to PM2.5, NO2, nitrous oxides, and carbon monoxide were associated with increased dementia risk, while findings regarding O3 were mixed.5

However, a study published in February 2022 reported that each 10-μg/m3 increase in the annual mean O3 exposure was associated with a 10.4% increase in the risk of cognitive impairment in a cohort of 9,544 older adults in China, highlighting the need for additional research to elucidate the potential impact of O3 on the risk of cognitive decline and dementia.6

Other research has demonstrated that improved air quality was associated with reduced dementia risk. Results published in January 2022 linked reductions in the risk of dementia to improvements in PM2.5 (HR, 0.80 per 1.78 μg/m3; 95% CI, 0.71–0.91) and NO2 (HR, 0.80 per 3.91 parts per billion; 95% CI, 0.71–0.90) in a cohort of 2239 older women in the US.7

To learn more about these findings and the pollution-dementia connection, we interviewed 2 researchers of the January 2022 study: Jiu-Chiuan Chen, MD, ScD, associate professor of preventive medicine at the Keck School of Medicine at the University of Southern California (USC) in Los Angeles and Diana Younan, PhD, MPH, an epidemiologist who was a senior research associate at USC at the time the study was conducted.

What does research suggest thus far about the relationship between air pollution and the risk for dementia, and what do your recent findings7 add to the conversation?

Dr Chen: The research so far has consistently shown that late-life exposures to outdoor air pollution, especially PM2.5, is harmful to aging brains and can even increase the risk [for] dementia. In our previous studies, we identified white matter as a novel target of air pollution neurotoxicity on brain aging.8

We also found that older women living in locations with higher levels of PM2.5 had more gray matter atrophy that spatially distributed in brain areas vulnerable to AD neuropathology.9 We further showed that such spatial pattern AD-related neurodegeneration led to greater declines in episodic memory in older women who lived in locations with higher PM2.5 levels.10 Our recent study also reported the association between NO2 exposure and smaller volumes of the prefrontal cortex and insula.11

Scientists have shown that improved long-term air quality may extend life expectancy in older populations, reduce mortality in adults, improve respiratory health in children, and increase birth weight in newborns. However, what is unknown—and what we were focusing on in our study—was whether improving air quality could improve brain health (i.e., lower the risk [for] dementia). Our study is one of the first to show that improving air quality over time may benefit the brain health of older women by lowering their [dementia risk].7

What are the proposed mechanisms driving the association between air pollution and dementia risk? 

Dr Chen: When air pollution is inhaled, the very small particles can penetrate the lungs and enter the circulatory system. Experimental studies in animals have shown that these “toxic” responses may weaken the blood-brain barrier and cause damage to the brain.12

Several scientists also believe that once in the airways or deep in the lung parenchyma, the particles may cause an inflammatory response, leading to activation of immune cells and overproduction of cytokines, which may migrate and enter the central nervous system to cause brain damage. Increasing evidence also suggests that the very small particles may bypass the lungs and blood-brain barrier through the nasal cavity into the olfactory bulb. Additionally, others have speculated that the fine particles may increase the risk for dementia via damage to the vascular systems, although such studies on older populations remain limited.13

What broad measures are needed to address this issue? 

Dr Younan: The health benefits seen in our study were a result of decreasing levels of both fine particulate matter and traffic related air pollution (NO2) across the US, which were likely due to national policies and strategies aimed at regulating pollution from stationary sources such as power plants and factories and mobile sources such as vehicles. We and others have found evidence suggesting neurotoxic effects of air pollution even at low levels of exposures. Therefore, we believe that continuing these regulatory efforts are important to help older Americans sustain their brain health.  

How should clinicians advise their patients about the link between air pollution and dementia risk?

Dr Chen: Scientists have documented that air pollution can be harmful to the brain for more than 10 years. The 2020 Lancet Commission report1 considered air pollution exposure in late life as an important modifiable risk factor for dementia, thus it is important for clinicians to educate themselves about [the] link between air pollution exposure and resulting damage to aging brains. 

Physicians can also encourage patients to maintain awareness of daily air quality via email notification, relevant websites, and weather broadcasts, especially for the elderly and those with heart or lung diseases or diabetes. This would enable patients to plan their outdoor activities accordingly and make efforts to reduce their personal exposure to air pollution, such as avoiding physical activities near busy roadways and keeping air vents and windows closed while driving.

References

  1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet CommissionLancet. Published online July 30, 2020. doi:10.1016/S0140-6736(20)30367-6
  2. Shi L, Steenland K, Li H, et al. A national cohort study (2000-2018) of long-term air pollution exposure and incident dementia in older adults in the United StatesNat Commun. Published online November 19, 2021. doi:10.1038/s41467-021-27049-2
  3. Mortamais M, Gutierrez LA, de Hoogh K, et al. Long-term exposure to ambient air pollution and risk of dementia: Results of the prospective Three-City Study. Environ Int. Published online January 20, 2021. doi:10.1016/j.envint.2020.106376
  4. Iaccarino L, La Joie R, Lesman-Segev OH, et al. Association between ambient air pollution and amyloid positron emission tomography positivity in older adults with cognitive impairment. JAMA Neurol. Published online November 30, 2020. doi:10.1001/jamaneurol.2020.3962
  5. Peters R, Ee N, Peters J, Booth A, Mudway I, Anstey KJ. Air pollution and dementia: A systematic reviewJ Alzheimers Dis. Published online August 13, 2019. doi:10.3233/JAD-180631
  6. Gao Q, Zang E, Bi J, et al. Long-term ozone exposure and cognitive impairment among Chinese older adults: A cohort study. Published online January 1, 2022. Environ Int. doi:10.1016/j.envint.2021.107072
  7. Wang X, Younan D, Millstein J, et al. Association of improved air quality with lower dementia risk in older women. Published online January 4, 2022. Proc Natl Acad Sci U S A. doi:10.1073/pnas.2107833119
  8. Chen JC, Wang X, Wellenius GA, et al. Ambient air pollution and neurotoxicity on brain structure: Evidence from women’s health initiative memory study. Ann Neurol. Published online July 28, 2015. doi:10.1002/ana.24460
  9. Younan D, Wang X, Casanova R, et al. PM2.5 associated with gray matter atrophy reflecting increased Alzheimers risk in older women. Neurology. Published online November 18, 2020. doi:10.1212/WNL.0000000000011149
  10. Younan D, Petkus AJ, Widaman KF, et al. Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer’s disease. Brain. Published online January 1, 2020. doi:10.1093/brain/awz348
  11. Petkus AJ, Resnick SM, Wang X, et al. Ambient air pollution exposure and increasing depressive symptoms in older women: The mediating role of the prefrontal cortex and insula. Published online February 3, 2022. Sci Total Environ. doi:10.1016/j.scitotenv.2022.153642
  12. Liu Q, Shkirkova K, Lamorie-Foote K, et al. Air pollution particulate matter exposure and chronic cerebral hypoperfusion and measures of white matter injury in a murine modelEnviron Health Perspect. Published online August 23, 2021. doi:10.1289/EHP8792
  13. Jankowska-Kieltyka M, Roman A, Nalepa I. The air we breathe: Air pollution as a prevalent proinflammatory stimulus contributing to neurodegeneration. Front Cell Neurosci. Published online June 24, 2021. doi:10.3389/fncel.2021.647643