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Original Investigation
November 30, 2020

Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment

Author Affiliations
  • 1Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco
  • 2Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
  • 3Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco
  • 4Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island
  • 5Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco
  • 6Department of Medicine, Virginia Commonwealth University, Richmond
  • 7Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine in St Louis, St Louis, Missouri
  • 8Division of Research, Kaiser Permanente, Oakland, California
  • 9Department of Public Health Sciences, University of California, Davis, Davis
  • 10Medical and Scientific Relations Division, Alzheimer’s Association, Chicago, Illinois
  • 11Department of Biostatistics, Brown University School of Public Health, Providence, Rhode Island
  • 12Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco
  • 13Associate Editor, JAMA Neurology
JAMA Neurol. 2021;78(2):197-207. doi:10.1001/jamaneurol.2020.3962
Key Points

Question  Does living in areas with greater air pollution increase the likelihood of positive amyloid positron emission tomography (PET) scan results in older adults with cognitive impairment in the US?

Findings  In this cross-sectional study of 18 178 individuals with cognitive impairment, people living in areas with worse air quality were more likely to have positive amyloid positron emission tomography scan results; specifically, higher PM2.5 concentrations appeared to be associated with brain amyloid-β plaques, a signature characteristic of Alzheimer disease. This association was dose dependent and statistically significant after adjusting for demographic, lifestyle, and socioeconomic factors as well as medical comorbidities.

Meaning  Findings of this study suggest that exposure to air pollution is associated with amyloid-β pathology in older adults with cognitive impairment; such information should be considered in public health policy decisions and should inform lifetime risk of Alzheimer disease and dementia.

Abstract

Importance  Amyloid-β (Aβ) deposition is a feature of Alzheimer disease (AD) and may be promoted by exogenous factors, such as ambient air quality.

Objective  To examine the association between the likelihood of amyloid positron emission tomography (PET) scan positivity and ambient air quality in individuals with cognitive impairment.

Design, Setting, and Participants  This cross-sectional study used data from the Imaging Dementia—Evidence for Amyloid Scanning Study, which included more than 18 000 US participants with cognitive impairment who received an amyloid PET scan with 1 of 3 Aβ tracers (fluorine 18 [18F]–labeled florbetapir, 18F-labeled florbetaben, or 18F-labeled flutemetamol) between February 16, 2016, and January 10, 2018. A sample of older adults with mild cognitive impairment (MCI) or dementia was selected.

Exposures  Air pollution was estimated at the patient residence using predicted fine particulate matter (PM2.5) and ground-level ozone (O3) concentrations from the Environmental Protection Agency Downscaler model. Air quality was estimated at 2002 to 2003 (early, or approximately 14 [range, 13-15] years before amyloid PET scan) and 2015 to 2016 (late, or approximately 1 [range, 0-2] years before amyloid PET scan).

Main Outcomes and Measures  Primary outcome measure was the association between air pollution and the likelihood of amyloid PET scan positivity, which was measured as odds ratios (ORs) and marginal effects, adjusting for demographic, lifestyle, and socioeconomic factors and medical comorbidities, including respiratory, cardiovascular, cerebrovascular, psychiatric, and neurological conditions.

Results  The data set included 18 178 patients, of which 10 991 (60.5%) had MCI and 7187 (39.5%) had dementia (mean [SD] age, 75.8 [6.3] years; 9333 women [51.3%]). Living in areas with higher estimated biennial PM2.5 concentrations in 2002 to 2003 was associated with a higher likelihood of amyloid PET scan positivity (adjusted OR, 1.10; 95% CI, 1.05-1.15; z score = 3.93; false discovery rate [FDR]–corrected P < .001; per 4-μg/m3 increments). Results were similar for 2015 to 2016 data (OR, 1.15; 95% CI, 1.05-1.26, z score = 3.14; FDR-corrected P = .003). An average marginal effect (AME) of +0.5% (SE = 0.1%; z score, 3.93; 95% CI, 0.3%-0.7%; FDR-corrected P < .001) probability of amyloid PET scan positivity for each 1-μg/m3 increase in PM2.5 was observed for 2002 to 2003, whereas an AME of +0.8% (SE = 0.2%; z score = 3.15; 95% CI, 0.3%-1.2%; FDR-corrected P = .002) probability was observed for 2015 to 2016. Post hoc analyses showed no effect modification by sex (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.04; z score = 1.13; FDR-corrected P = .56]; 2015-2016: β = 1.02 [95% CI, 0.98-1.07; z score = 0.91; FDR-corrected P = .56]) or clinical stage (2002-2003: interaction term β = 1.01 [95% CI, 0.99-1.03; z score = 0.77; FDR-corrected P = .58]; 2015-2016: β = 1.03; 95% CI, 0.99-1.08; z score = 1.46; FDR-corrected P = .47]). Exposure to higher O3 concentrations was not associated with amyloid PET scan positivity in both time windows.

Conclusions and Relevance  This study found that higher PM2.5 concentrations appeared to be associated with brain Aβ plaques. These findings suggest the need to consider airborne toxic pollutants associated with Aβ pathology in public health policy decisions and to inform individual lifetime risk of developing AD and dementia.

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