Article In Brief
New research suggests exposure to bad air pollution may be among a host of environmental, lifestyle, and genetic factors that increase a person's chances of cognitive impairment as they age.
A growing body of research suggests that air pollution may play a role in the development of cognitive impairment, though many questions remain to be answered.
The latest suggestion of a deleterious effect comes from a study of older adults already diagnosed with mild cognitive impairment. Participants who underwent an amyloid PET scan that showed signs of amyloid-beta (Abeta) pathology were more likely to have lived in areas with higher levels of air pollution.
The study does not prove a cause and effect between air pollution exposure and risk for Alzheimer's disease (AD) or other dementia, but it does suggest that exposure to bad air pollution may be among a host of environmental, lifestyle, and genetic factors that increase a person's chances of cognitive impairment as they age.
Exposure to air pollution is already considered troublesome for the respiratory system, and increasingly evidence supports a link between air pollution and elevated risk for cardiovascular disease, including stroke.
“We are now starting to understand the extent to which air pollution is also associated with brain outcomes,” said the study's lead author, Leonardo Iaccarino, PhD, a postdoctoral fellow at the Memory and Aging Center at the University of California, San Francisco.
Dr. Iaccarino said one hypothesis, based in part on animal studies, based in part on animal studies, is that chronic exposure to air pollution, perhaps over decades, may trigger an inflammatory response that could make the brain more vulnerable to Alzheimer's pathology.
Many people can't choose where they live—whether near a busy highway or industrial center or in a less congested suburban or rural area— but policymakers and public officials can make regulations and set standards that promote cleaner air, the study authors suggested.
“Adverse effects of airborne toxic pollutants associated with Abeta pathology should be considered in public health policy decisions and should inform individual lifetime risk of developing AD and dementia,” the researchers concluded in a report published in February in JAMA Neurology.
The study authors explained that ambient air pollution is a mixture of particles and gases. Fine particulate matter and ground-level ozone are commonly used to measure air quality. Both “have a role in the global burden of disease and mortality and have been associated with an increased risk of cognitive decline, clinically diagnosed AD, and all-cause dementia in epidemiological studies,” the paper said. “The Lancet Commission 2020 update on dementia prevention, intervention, and care recently recognized exposure to polluted air as a modifiable risk factor for late-life cognitive decline.”
The latest study involved a cross-sectional secondary analysis of data obtained for the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Study, which included 18,000 participants from across the US who underwent a PET scan between February 2016 and January 2018 to assess accumulation of Abeta. The IDEAS study had enrolled Medicare beneficiaries ages 65 or older who were diagnosed with mild cognitive impairment (MCI) or dementia of an uncertain etiology following a comprehensive evaluation by a dementia specialist. The group was mostly White (86.8 percent) and were on average 75.8 years old.
The PET scans were rated as positive (61 percent) or negative (39 percent) by certified imaging specialists at each imaging site using tracer-specific criteria.
The researchers used residential zip codes and data on concentrations for fine particulate matter and ground-level ozone collected by the US Environmental Protection Agency (EPA) to calculate exposure to air pollution for two time periods—from 2002 to 2003, which was approximately 14 years before the PET scans—and 2015 to 2016, which was shortly before the scans were done.
“We found that older adults with cognitive impairment and who resided in areas of higher concentrations of (particulate matter) were more likely to have a positive amyloid PET scan,” the researchers reported. The association between exposure to air pollution and amyloid pathology held after researchers did statistical adjustments to account for possible confounding factors such as smoking, family history, and household income as well as medical comorbidities.
“These findings suggest that brain Abeta accumulation could be one of the biological pathways in the increased incidence of dementia and cognitive decline associated with exposure to air pollution,” the researchers said.
Participants who lived in areas with the highest concentration of particulate matter areas had a 10 percentage point higher probability of having amyloid pathology compared to those living in areas with the lowest air pollution, Dr. Iaccarino said, adding the elevated risk was associated with increased exposure to particulate matter, not ozone.
He said that more research is needed into environmental influences on brain health and cautioned that this study cannot be interpreted as meaning that “living in areas with higher air pollution will mean you develop Alzheimer's or other form of dementia in your lifetime.” He said that air quality, specifically in regards to fine particulate matter, improved in the US during the timespan of the study, he pointed out.
The findings are not necessarily generalizable because the study only included people who had cognitive impairment and presented to memory clinics. That could have caused a selection bias, the researchers noted. A different picture might have emerged if the study had enrolled people with seemingly healthy cognitive status. Also, the study looked at chronic exposure to air pollution, not the effects of being exposed to a defining event such as a wildfire.
While the study was not designed to pinpoint a mechanism by which exposure to chronic air pollution could affect the brain, “neuroinflammation and oxidated stress have been identified as the most likely biological mechanism in the adverse brain health effects of ambient air pollution, with microglia as the possible main cellular mediators of neurotoxic effects,” the paper said.
Even if a link between air pollution and risk for AD or other dementia is proven, it would be one of multiple risk factors that influence a person's cognitive health, said Joel Salinas, MD, MBA, Lulu P. and David J. Levidow assistant professor of neurology at NYU Langone Health.
“This (new) study is useful in moving the field toward understanding how environmental exposure can lead to cognitive decline,” he said.
But Dr. Salinas noted that with cross-sectional studies, “a limitation is that it is difficult to know what comes first—the chicken or the egg?” It's possible “people who are more likely to be vulnerable to these types of exposure are living in areas with high exposure,” he said.
Dr. Salinas has been part of a team studying the connection between exposure to small particulate matter and AD and related dementia using data from the Women's Health Initiative study. It found that people who are at higher exposures of air pollution in the form of fine particles are at a higher risk of memory decline, which seems to be due to a similar higher risk of early brain atrophy in areas specific to AD, he said.
Dr. Salinas is using the Framingham Heart Study database to examine social determinants of brain health, with a particular interest in the effects of social relationship factors such as social supports, social isolation, and loneliness. Dr. Salinas said the more that is being learned about AD and dementia, the clearer it becomes that “there is a lot of heterogeneity” in terms of risk factors and individual vulnerabilities.
Erin Kulick, PhD, assistant professor of epidemiology and biostatistics at Temple University, said new study was “a strong research paper and one of the first to look at a large population that is geographically diverse across the country,” though the cohort was lacking in racial diversity. Some of the other studies of the longer-term health effects of air pollution have focused on urban areas.
Dr. Kulick's research has found associations between residential exposure to traffic-related air pollution and risks for stroke, subclinical markers of cerebrovascular disease, and cognitive impairment and decline.
She said there is growing evidence of a “strong connection between air pollution and stroke and heart attack,” and she suspects that many of the same underlying processes that increase the risk of cardiovascular diseases in areas of higher air pollution may also put an individual at elevated risk for dementia.
While she said the mechanisms are not fully understood, “researchers are starting to look at whether air pollution is working through these other factors to cause cognitive decline and dementia.”
She is now conducting a study that utilizes a large database of hospitalizations for the state of New York to look for connections between air pollution, influenza-like illness, stroke and heart attack.
Drs. Iaccarino, Kulick, and Salinas disclosed no conflicts.