I live in Manhattan,
and I’m holding my breath.
Evidence that air
pollution can damage the brain along with the heart and lungs has been accumulating
for years. In the past decade, studies have linked exposure to high
concentrations of fine particles (<2.5µm) associated with combustion, in particular, to reduced cognitive
function in older adults, and to MRI evidence of more "silent strokes"
[See “Air
Pollution Also Not Good for Your Brain”]. Recent research suggests that air
pollution increases the risk of diabetes, which can have negative consequences
for the brain.
The latest round of
findings won’t have city dwellers breathing any easier. Over the past two years,
population studies in Taiwan, Sweden, and Canada have drawn explicit connections
between bad air and the end stage of such changes: dementia.
The most recent, an
analysis of more than 3,600 older women across the US published in Translational Psychiatry, indicated that
exposure to fine-particle pollution above Environmental Protection Agency
standards nearly doubles the
risk of a dementia diagnosis within the following decade.
Research into
environmental risk factors for dementia has burgeoned in recent years, says Tom
Russ of the University of Edinburgh. “It’s an area of growing interest, and
continues to pick up momentum."
A 2016 BMC Geriatrics review of environment-dementia
research that Russ co-authored included air
pollution on a "short list" of factors for which the evidence as
at least moderate. "Studies are consistent: The effects are all in the
same direction," he says. "It's plausible; we know that air pollution
is bad, and it’s easy to think of mechanisms by which it might affect the brain
adversely."
Road hazards
A study
just published in the Lancet is particularly
compelling, with caveats. The data base was enormous: nearly all the adults,
aged 20 to 50 and 55 to 85, who in 2001 had resided in Ontario, Canada, for 5
years or longer—6.6 million. The researchers found that those who lived close
(within 50 meters) to a roadway with heavy traffic had a 7 percent greater risk
of dementia, a decade later, than those who lived more than 300 meters away. For
people who didn't change their residence during the study, close proximity
raised the risk by 11 percent.
"The risk was
specific to dementia," says Ray
Copes, chief of environmental and occupational health at Public Health
Ontario, and an author of the study. "We didn't find any association with
the other two neurological conditions [Parkinson's disease and multiple
sclerosis] that we looked at.
"The other
important finding was a smooth gradient of risk: As you move closer to a major
traffic artery— 100-200 meters, 50-100 meters, less than 50 meters—the risk
increases continually."
The connection to
pollution was less than airtight, though. While increased concentration of airborne
gases and particles is clearly a consequence of proximity to heavy traffic,
it's not the only one, Copes acknowledges. There's also a gradient of noise,
which has likewise been linked to cognitive compromise, and such
location-linked factors as access to exercise and socioeconomic status that may
play a role.
"We can't say
with precision that [the increased risk of dementia] is due to air pollution,
or to one particular pollutant, but it's a reasonable hypothesis," he
says.
To Lilian Calderόn-Garcidueñas, primary investigator at the Environmental Neuroprotection
Laboratory at the University of Montana,
"this paper is very important.
It touches specifically on an issue critical in urban areas, from a medical
point of view: a clear association between where you live and the risk of
dementia. In a megacity, you're never far away from high-traffic streets.
"It's extremely
relevant to us in daily practice," says Calderόn-Garcidueñas,
who is a physician as well as a researcher.
In themselves, population
studies like the Ontario paper fall short of establishing whether and how air
pollution connects to dementia, says Russ. "They look at a variety of air
pollution measures, nitrogen oxides, ozone, particulate matter, which are more
or less correlated but don't have the same effect on the brain. It's unclear
which component might be involved."
To clarify such
issues, "a broad approach is needed... mechanistic work examining what
pollutants can do [some leading contenders are neuroinflammation, oxidative
stress, epigenetic changes, and neurovascular compromise], studies that
characterize people, their residential histories and exposure throughout
life," he says.
“We know that
neurodegenerative changes start decades before the clinical onset of dementia
symptoms. We don’t know when air pollution exposure might be important. It
might start off neurodegeneration, or play a role throughout the process,” Russ
says.
Children at risk
Recent research suggests
that the impact begins early. “I’m going 50 years before the clear-cut
diagnosis of dementia, showing these changes are already present in children
and adolescents,” says Calderόn-Garcidueñas.
She and colleagues
have published research in this area for more than a decade, including papers
in 2016 that showed changes
in cerebrospinal-fluid biomarkers of Alzheimer’s risk (including
concentration of amyloid-β and
phosphorylated tau protein) in young Mexico City residents exposed to high
levels of small airborne particles, compared with non-city children. In
neuroanatomical and cognitive studies, “we’re picking up very subtle alterations
in teens, in 9-year-olds” that seem to prefigure what is seen, in extreme form,
in Alzheimer’s patients many years later, she says.
A 2016 post-mortem
analysis found ultrafine particles (<100nm in diameter) of magnetite—highly
magnetized iron oxide—in the brains of people exposed to high air pollution
levels in Mexico City and Lancaster, UK. Their size and shape suggested they
were products of high-temperature combustion, as might occur in an automobile
engine.
“These smaller
particles are more likely to get into the brain,” [possibly via the olfactory
nerve] says Calderόn-Garcidueñas, who was also an author of
that paper. “They may be involved in the production of free radicals.”
Magnetite was seen in
brain of adolescents and children as young as 3 years, in the study. [A 2017
UNICEF report, “Clear
the Air for Children,” said that
about 2 billion children are exposed to hazardous air pollution levels; for 300
million of them, pollutants in the air they breathe exceed World Health
Organization limits by six-fold.]
A breath of fresher air
Although biological
and epidemiological evidence linking airborne gases and particles to dementia
is considerable, it doesn’t yet add up to a smoking gun, experts interviewed
for this article agree. But it’s sufficiently strong to “make the argument that
further control of air quality is desirable from a public health perspective,
and that long-term exposure, not brief exacerbations, are what’s most important,”
says Copes.
For urban planners, findings
like his suggest that schools, homes, and offices might best be built at a
slight remove from roadways, he says. “Relatively small setbacks make a big
difference in the gradient of exposure.” Buildings designed to be less permeable to
pollution could offer another layer of protection.
Not everyone is equally
vulnerable to pollution, Calderόn-Garcidueñas points out. “Many have
factors of risk that accelerate the [neurodegenerative] process.” For people who carry the APOE4 allele, the
strongest genetic risk factor for Alzheimer’s, exposure may have heightened
impact, she says. Cigarette smoking, female gender, obesity, and psychosocial
stress appear to multiply the danger as well.
Air pollution is part of a bigger picture,
Russ emphasizes. As more detailed data is gathered about environment, biology,
and individual factors that converge in dementia risk, “we may move toward a
personalized medicine approach to prevention,” he says.