Some of the risk of dementia stems from a person’s environment, but teasing out the specific factors involved has been difficult. A study in the January 4 issue of The Lancet shines a spotlight on pollutants. Researchers led by Hong Chen at Public Health Ontario, a government agency in Toronto, followed nearly all older adults living in that province of Canada for 11 years, and found that the risk of dementia edged up the closer people lived to busy roads or highways. Though the effect was small, it could account for as many as 10 percent of new dementia cases among those living within 50 meters of a busy road, the authors estimated. Pollution is likely a major factor, while noise and lost sleep might also play a role, the authors speculated. Taken together with other studies linking air pollutants to cognitive decline and neuroinflammation, the results suggest that chronic exposure to traffic emissions represents a significant public health risk that should be addressed, the authors note.
Others agreed, though they noted the need to replicate the findings to rule out confounding factors. If confirmed, the data suggest a major global health concern for millions of people, Walter Rocca at the Mayo Clinic in Rochester, Minnesota, wrote to Alzforum (see full comment below). In an accompanying Lancet editorial, Lilian Calderón-Garcidueñas at the University of Montana, Missoula, and Rodolfo Villarreal-Ríos at the University of the Valley of Mexico, Mexico City, went further, suggesting the results are already strong enough to guide emissions policy. “We must implement preventive measures now, rather than take reactive actions decades from now,” they wrote.
A number of previous studies have reported an association between air pollution from traffic and poor cognitive function in older adults (see Ranft et al., 2009; Power et al., 2011; Wellenius et al., 2012). An examination of 4,000 Germans over the age of 50 found more diagnoses of mild cognitive impairment among those living closest to traffic (see Tzivian et al., 2016). Longitudinal studies of thousands of people in Europe and North America correlated traffic-related air pollution with greater cognitive decline and a higher risk of Alzheimer’s disease (see Feb 2012 news; Jung et al., 2015; Oudin et al., 2016).
Chen and colleagues accessed data from Ontario’s Registered Persons Database, which includes nearly all 13 million residents of the province. The authors identified 2.2 million people who were between the ages of 55 and 85 in 2001 and did not have dementia, PD, or MS at that time, and tracked dementia incidence over 11 years. About 20 percent of the cohort lived in rural areas, while nearly half lived within 200 meters of a major roadway.
Almost a quarter of a million people developed dementia. Living closer to busy roadways, such as highways and arterial roads within cities, nudged up risk. Those within 100-200 meters of a main thoroughfare had a hazard ratio of 1.02 for dementia compared with those farther away, while for those within 50-100 meters the risk bumped up to 1.04. For those nearer than 50 meters, which comprised about 20 percent of the population, the risk reached 1.07, and up to 1.12 in urban regions and among people who had never moved.
Although modest, the increased risk was robust. Adjusting for smoking, obesity, physical activity, education, and other factors did not budge the numbers. Likewise, no association with socioeconomic status, as measured by neighborhood wealth or access to health care, emerged. The authors found no association between proximity to traffic and incident Parkinson’s disease (though see Ritz et al., 2016), or new cases of multiple sclerosis in people between the ages of 20 and 50. However, because there were only about 32,000 new cases of PD and 9,000 of MS, the statistical power to find an association was less than for dementia, the authors noted.
Looking for the source of the association between traffic and dementia, Chen and colleagues obtained satellite sensor and chemical data that allowed them to estimate regional concentrations of two common traffic-related air pollutants, nitrogen dioxide and fine particulate matter less than 2.5 μm in diameter. Adjusting the hazard ratios to account for these exposures attenuated the risk from traffic, suggesting these two pollutants explained some, but not all, of the association. Co-author Ray Copes at Public Health Ontario noted the study did not measure other potential toxic pollutants from vehicles, such as ultrafine particles. In future work, the authors plan to examine which components of traffic and air pollution most contribute to risk. Other studies have found that air pollutants can trigger neuroinflammation and oxidative stress in the brain, as well as increased microvascular infarcts and Aβ accumulation (see Calderón-Garcidueñas et al., 2008; Levesque et al., 2011; Wilker et al., 2015).
Commenters found the data intriguing. Deborah Blacker at Harvard University praised the methodological rigor of the study and the multiple sensitivity analyses, but noted it remains possible that living near major roadways serves as a proxy for some other factor they didn’t account for, such as individual incomes. She believes more studies are needed. Kenneth Langa, University of Michigan, Ann Arbor, suggested that though socioeconomic hardship did not relate to roadside living in Ontario, poor people might tend to live in more polluted environments elsewhere. “This paper raises the possibility that living in more polluted regions may be one cause for the clear socioeconomic-based differences in dementia risk globally,” Langa wrote to Alzforum.
Other groups are already planning similar studies. In one such effort, researchers led by Lianne Sheppard at the University of Washington, Seattle, and Ge (Gail) Li at the VA Puget Sound are placing devices around Seattle to directly measure the level of specific air pollutants in different neighborhoods. Exposures will be correlated with dementia incidence in the Adult Changes in Thought (ACT), a large longitudinal study, noted colleague Eric Larson at the Group Health Research Institute, Seattle. “This research area is beginning to emerge as much more interesting than any of us thought. I was excited to see this paper,” Larson said.
Researchers are particularly intrigued by the findings because air pollution represents a modifiable risk factor. Rocca believes that improved air quality in high-income countries in recent decades might explain some of the drop in dementia incidence (see Nov 2016 news). “If this hypothesis is correct, further emission control policies and traffic reduction interventions may impact the future risk of dementia,” he wrote. Similarly, Larson suggested that air pollution might be a factor in the increasing rates of dementia seen in less developed parts of the world, where industrialization is on the rise.—Madolyn Bowman Rogers
The paper reports the findings of a study conducted in Ontario, Canada, using linkage techniques across multiple databases. The study was possible because of the unique availability of routinely collected medical and environmental data for millions of residents. The study is an excellent example of the power of linking passively collected data over large populations or regions (records-linkage systems).
The authors reported that living near major highways is associated with an increased risk of dementia, but not of Parkinson’s disease or multiple sclerosis, in a 10-year cohort study. The authors reported a "dose-response" risk for dementia: the closer the person lived to a major roadway, the higher their risk. The mechanism remains unclear, but the authors suggest it might relate to air pollution or to the effects of noise or stress on the brain. Even though the magnitude of the relative risk was moderate (7 to 12 percent increased hazard ratios for living less than 50 meters from a major road), up to 7-11 percent of the cases of dementia that developed during the study in persons who lived less than 50 meters from a major road was attributable to (or explained by) the traffic exposure. Therefore, if the findings are not due to some unrecognized confounding mechanisms, and can be replicated in additional studies, then they create a major global health concern for millions of people, as suggested by the editorial accompanying the paper.
The authors of the accompanying editorial suggested that factors such as sex, body-mass index, and genetic variants may modify the response of specific individuals to air pollutants or to noise. In particular, they mentioned that women may be more sensitive than men.
The findings from the Ontario study may relate to findings of decreased dementia incidence in recent years. A growing body of epidemiologic evidence indicates a decline in the incidence or prevalence of dementia in high income countries in the past 25 years. This decline is in part explained by the reduction of known cardiovascular risk factors or events, by improved education, and by increased wealth. However, part of the decline remains unexplained. It is conceivable that improved air quality in high income countries may have contributed to the decline. The changes in type of vehicles, availability of less polluting fuels, emission control technologies, and emission control policies may have impacted the level or air pollution for people living near major roads and in major urban centers in the more recent decades. If the hypothesis is correct, further emission control policies and traffic reduction interventions may impact the future risk of dementia.
The culprit may indeed be air pollutants. But there's a potential confounder that, I would suggest, is quite plausible. Who wants to live near a major highway? Not me, nor most people I would think. Money buys privilege, so real property values near highways are lower than those in the hinterlands. Ergo, lower-income people live nearer highways. Lower-income people have poorer access to healthcare and poorer health maintenance practices They smoke more and eat less heart-healthy diets, etc., etc. Could these factors alone not account for the increased incidence of dementia in such folks? I'm glad to hear that my friends Gail Li and Eric Larson are investigating this topic in the ACT cohort. The health records and exquisite personal data available in that cohort should help "clear the air" on whether the highway proximity finding is really attributable to pollutants. We all know that association does not equate to causality!