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Particulate air pollutants, risk of cognitive disorders, and neuropathology in the elderly

Principal Investigator: 

University of Southern California

This New Investigator Award study evaluated whether ambient PM exposure increases the risk for dementia and mild cognitive impairment, using data from the Women’s Health Initiative Memory Study (WHIMS) cohort.

Funded under
In review

Abstract for HEI Annual Conference 2015

Neurotoxicity of Exposure to Ambient Fine Particles on Brain Structure: Evidence from Women’s Health Initiative Memory Study
Chen JC, Wang X, Serre ML, and Espeland MA
University of Southern California, Los Angeles; University of North Carolina School of Public Health, Chapel Hill, North Carolina; Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Background    Despite growing data supporting the concept that exposure to ambient particulate matter (PM) represents a novel and potentially amendable environmental determinant of brain aging, the brain structure and possible neuropathological damages underlying the PM-associated neurotoxic effects on cognitive decline remain unclear. An interesting pattern of exposure-outcome association was revealed in our previous analyses on diesel PM exposures, suggesting neurotoxic effects on gray matter with local compensatory hypertrophy of white matter among older women residing in neighborhood with higher ambient concentration estimated by the National Air Toxics Assessment Program.

Methods    We conducted a prospective study on 1403 community-dwelling older women enrolled in the Women's Health Initiative Memory Study (WHIMS) in 1996-1998. Structural brain MRI scans were performed at age of 71–89 years in 2005-2006 to obtain volumetric measures of normal-appearing gray matter and white matter as well as small-vessel ischemic disease. Given the residential histories and air monitoring data, we used a spatiotemporal model to estimate the cumulative exposures to fine particulate matter (PM2.5) in 1999-2006. Multiple linear regression was employed to evaluate the putative adverse PM2.5 effects, adjusting for intracranial volumes and potential confounders.

Results    Older women with higher PM2.5 exposures had smaller white matter, with no statistically significant differences in gray matter volumes, independent of geographic region, demographic features, socioeconomic status, lifestyle metrics, and clinical characteristics including cardiovascular risk factors. For each inter-quartile increment (3.49-µg/m3) of cumulative PM2.5 exposure, the multicovariate-adjusted mean volume (95% confidence interval) of normal-appearing white matter was lowered by 4.47 (2.27-6.67) cm3 in association brain (frontal + parietal + temporal lobes) and by 6.23 (3.72-8.74) cm3 in total brain, equivalent to 1-2 years of brain aging. The suggested adverse PM2.5 effects on WM atrophy were present in frontal and temporal lobes and corpus callosum (all p-values <0.0001). Hippocampal volumes and small vessel ischemic disease volumes measured in the whole brain, gray matter, or white matter did not differ by residential exposures to ambient PM2.5.

Conclusions    PM2.5 exposure may contribute to white matter loss in healthy older women. Future studies need to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other white matter neuropathologies. Substantiating the evidence for exposure-induced structural neurotoxicity to white matter may have broad implications for various neurodevelopmental deficits and neurological diseases linked to PM in epidemiologic studies. 


Chen JC, Wang X, Wellenius GA, Serre ML, Driscoll I, Casanova R, McArdle JJ, Manson JE, Chui HC, Espeland MA. Ambient air pollution and neurotoxicity on brain structure: Evidence from women's health initiative memory study. Ann Neurol. 2015 Sep;78(3):466-476.


Poster by Chen et al., 2015 Annual Conference