TY - JOUR
T1 - Association between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults with Cognitive Impairment
AU - Iaccarino, Leonardo
AU - La Joie, Renaud
AU - Lesman-Segev, Orit H.
AU - Lee, Eunice
AU - Hanna, Lucy
AU - Allen, Isabel E.
AU - Hillner, Bruce E.
AU - Siegel, Barry A.
AU - Whitmer, Rachel A.
AU - Carrillo, Maria C.
AU - Gatsonis, Constantine
AU - Rabinovici, Gil D.
N1 - Funding Information:
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.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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 18178 patients, of which 10991 (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 PM2.5concentrations 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/m3increments). 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/m3increase in PM2.5was 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 O3concentrations was not associated with amyloid PET scan positivity in both time windows. Conclusions and Relevance: This study found that higher PM2.5concentrations 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..
AB - 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 18178 patients, of which 10991 (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 PM2.5concentrations 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/m3increments). 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/m3increase in PM2.5was 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 O3concentrations was not associated with amyloid PET scan positivity in both time windows. Conclusions and Relevance: This study found that higher PM2.5concentrations 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..
UR - http://www.scopus.com/inward/record.url?scp=85097499607&partnerID=8YFLogxK
U2 - 10.1001/jamaneurol.2020.3962
DO - 10.1001/jamaneurol.2020.3962
M3 - Article
C2 - 33252608
AN - SCOPUS:85097499607
SN - 2168-6149
VL - 78
SP - 197
EP - 207
JO - JAMA Neurology
JF - JAMA Neurology
IS - 2
ER -