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

Educational Objective
To evaluate whether living in areas with greater air pollution increases the likelihood of positive amyloid positron emission tomography scan results in older adults with cognitive impairment in the United States.
1 Credit CME
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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Article Information

Accepted for Publication: August 13, 2020.

Corresponding Author: Leonardo Iaccarino, PhD, Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA 94158 (leonardo.iaccarino@ucsf.edu).

Published Online: November 30, 2020. doi:10.1001/jamaneurol.2020.3962

Author Contributions: Dr Iaccarino had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Iaccarino, La Joie, Whitmer, Carrillo, Gatsonis, Rabinovici.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Iaccarino, Lee, Allen, Carrillo.

Critical revision of the manuscript for important intellectual content: Iaccarino, La Joie, Lesman-Segev, Hanna, Hillner, Siegel, Whitmer, Carrillo, Gatsonis, Rabinovici.

Statistical analysis: Iaccarino, La Joie, Lesman-Segev, Lee, Hanna, Allen, Whitmer, Carrillo, Gatsonis.

Obtained funding: Whitmer, Gatsonis, Rabinovici.

Administrative, technical, or material support: Hillner, Carrillo, Gatsonis.

Supervision: Carrillo, Rabinovici.

Conflict of Interest Disclosures: Ms Hanna reported receiving grants from the American College of Radiology. Dr Hillner reported receiving grants from the Alzheimer's Association. Dr Siegel reported receiving grants from the American College of Radiology during the conduct of the study and ImaginAb Inc; personal fees from Avid Radiopharmaceuticals, Curium Pharma, GE Healthcare, Siemens Healthineers, and Capella Imaging outside the submitted work; and grants and personal fees from Progenics Pharmaceuticals and Blue Earth Diagnostics. Dr Whitmer reported receiving grants from the National Institutes of Health (NIH) and the Alzheimer’s Association. Dr Carrillo reported being a full-time employee of the Alzheimer’s Association. Dr Gatsonis reported receiving grants from the American College of Radiology during the conduct of the study. Dr Rabinovici reported receiving grants from the American College of Radiology, Alzheimer's Association, Avid Radiopharmaceuticals, GE Healthcare, and Life Molecular Imaging during the conduct of the study; personal fees from GE Healthcare, Axon Neurosciences, Eisai, Merck, and Johnson & Johnson; and grants from the NIH, Rainwater Charitable Foundation, Association for Frontotemporal Degeneration, and Michael J. Fox Foundation outside the submitted work. No other disclosures were reported.

Funding/Support: The IDEAS Study was funded by the Alzheimer’s Association, the American College of Radiology, Avid Radiopharmaceuticals Inc, GE Healthcare, and Life Molecular Imaging (formerly Piramal Imaging).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: Dr Rabinovici is an Associate Editor of JAMA Neurology but was not involved in any of the decisions regarding review of the manuscript or its acceptance.

Additional Contributions: We thank Amelia Strom, BS, for assistance with manuscript drafting; she received no additional compensation, outside of her usual salary, for her contributions. We thank all of the IDEAS participants, their families, as well as all the dementia and imaging specialists who contributed to the study.

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