Levels of Particulate Matter Below Regulatory Standards Increase Risk of Alzheimer Disease


Researchers from USC propose a direct neurotoxic effect of particulate matter smaller than 2.5 μm.

Diana Younan, PhD, research associate, University of Southern California

Diana Younan, PhD

A recent study published in Neurology suggests that progressive brain atrophy predictive of Alzheimer Disease (AD) is associated with late-life exposure to particulate matter with aerodynamic diameters <2.5-μm (PM2.5).

Longitudinal analyses showed that for each interquartile range (IQR) increase (IQR, 2.82- μg/m3) of PM2.5, the associated risk of developing AD increased by 24% (hazard ratio [HR], 1.24; 95% CI, 1.14–1.34) over a 5-year period, as assessed by increased AD pattern similarity (AD-PS) scores. This association remained within levels of PM2.5 below US regulatory standards (<12-μg/m3).1

Principal author Diana Younan, PhD, research associate, University of Southern California, stated in a related release that the “findings have important public health implications because not only did we find brain shrinkage in women exposed to the highest levels of PM2.5 pollution but we also found it in women exposed to levels lower than those that the EPA considers safe.”2

Younan and colleagues investigated data from 1365 women free of dementia with a mean age of 77.9 years (standard deviation [SD], 2.7) that participated in the WHIMS Magnetic Resonance Imaging (WHIMS MRI) study. MRI data at baseline and after 5 years was investigated. AD-PS scores—which have been shown to be associated with known risk factors of AD and poor cognitive function—were developed by a supervised machine learning algorithm by comparison of MRI data from the AD Neuroimaging Initiative of gray matter atrophy in areas vulnerable to AD such as the amygdala, hippocampus, thalamus, midbrain, parahippocampal gyrus, and inferior temporal lobe areas.

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In longitudinal analysis, IQR-increments were significantly associated with a 0.031 (β = 0.031; 95% CI, 0.017–0.046) increase in AD-PS score. In fully adjusted models the association was 0.026 (95% CI, 0.009–0.043), which correlates to the 24% increase of AD risk. This association remained after adjusting for socio-demographics, lifestyle, and clinical characteristics including cerebrovascular factors such as white matter lesion volume and stroke, challenging previous studies that have proposed a cerebrovascular mechanism of PM2.5 damage leading to brain atrophy. Instead, Younan and colleagues favor the theorized mechanism that PM2.5 directly contributes to the neurodegenerative process of dementia via a neurotoxic effect on brain structure.

Sensitivity analyses confirmed the positive association between PM2.5 and AD-PS score after adjusting for baseline AD-PS scores. No association was seen between PM2.5 and baseline AD-PS score in cross sectional analyses (β = –0.004; 95% CI, –0.019 to 0.011). 

Previous analyses of WHIMS MRI include region-of-interest analyses that showed residence in areas with higher PM2.5 was associated with smaller total brain and white matter volumes, and that residing in places with >12-μg/m3 concentrations of PM2.5 increased the risk of global cognitive decline by 81% and all-cause dementia by 92%.3

Younan and colleagues call for future studies “to fully investigate whether the neurodegenerative effects of late-life exposures to airborne particles may be contributed by or independent of cerebrovascular damage before or during late life...to replicate these results and to thoroughly explore other measures of cerebrovascular damage that may not be captured by white matter lesions and were not explored in our study (e.g., microbleeds; lacunar infarcts).”

1. 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
2. Hopper L. Does air pollution increase women’s risk of dementia? HSC News. November 20, 2020. Accessed December 2, 2020. https://hscnews.usc.edu/does-air-pollution-increase-womens-risk-of-dementia
3. Chen J, Wang X, Wellenius GA, et al. Ambient air pollution and neurotoxicity on brain structure: Evidence from women’s health initiative memory study. Ann Neurol. 2015;78(3):466–476. doi: 10.1002/ana.24460
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