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Air Pollution Found to Nearly Double Women’s Risk of Dementia

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BY SARAH OWENS

Women who live in areas of the United States where levels of fine particulate matter in the air exceed Environmental Protection Agency (EPA) standards had nearly double the risk of developing global cognitive decline and all-cause dementia, and carrier status for apolipoprotein e4 appeared to exacerbate this risk, according to a new study published on January 31 in Translational Psychiatry.

The association between environmental factors and dementia is poorly understood, but epidemiologic evidence and preliminary findings from animal models suggest that fine particulate matter (PM), or air pollutants with aerodynamic diameters < 2.5 microns (PM2.5), have neurotoxic effects. The current study suggests that long-term exposure to PM can accelerate global decline and dementia.

"The association between PM exposure and increased dementia risk suggests that the global burden of disease attributable to PM pollution has been underestimated, particularly in regions with large populations exposed to high ambient PM," the study authors, led by Mafalda Cacciottolo, PhD, postdoctoral research associate at the Leonard Davis School of Gerontology at the University of Southern California, wrote.

The study combined a neuroepidemiologic analysis of a prospective cohort of US women to investigate the strength of the association and experiments on transgenic mice to investigate possible underlying mechanisms. Researchers analyzed data from the Women's Health Initiative Memory Study (WHIMS), a prospective nationwide cohort of women in the United States, ages 65-74, who were free of dementia at the beginning of the study. WHIMS participants had undergone annual screenings for global cognitive function plus neuropsychological and functional assessments, which blinded raters used to diagnose dementia and global cognitive decline.

The researchers used a statistically validated model incorporating monitoring data from the US EPA Air Quality System to estimate ambient levels of PM2.5 at all residential locations in the WHIMS study over a three-year period beginning in 1999 or 2000, accounting for relocations. They classified three-year exposures as "high" if they exceeded the EPA's National Ambient Air Quality Standards for PM2.5. Then they used time-to-event analyses to evaluate the link between long-term PM exposure and adverse cognitive outcomes.

They found that that women who lived in areas with high PM exposures over a three-year period had a significantly increased risk for global cognitive decline and all-cause dementia. For women living in high PM areas, the hazard ratio (HR) for global cognitive decline increased by 81 percent, while the HR for all-cause dementia increased by 92 percent. Those with the APOE e4 allele had the highest increased risks (HR of 3.95 for global cognitive decline and 2.95 for dementia).

Supplemental experiments on transgenic mice offer clues about the underlying mechanisms of the association between PM and cognitive decline. Mice who were exposed to PM over 15 weeks had increased cerebral beta-amyloid production, increased amyloid-beta oligomers, and selective atrophy of hippocampal neurites. The researchers hypothesized that these effects, when induced by PM, lead to cognitive decline.

The researchers noted, among other limitations, that the study of women may not be generalizable to men. In addition, they said, their analysis did not include information on the type of particles, emission sources, or interaction with other pollutants; and they only used data on PM exposure after 1999, a time period when air pollution has begun to decline, so long-term PM exposure may have been underestimated.

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