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

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 PARTICIPANTSThis 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 [ 18 F]-labeled florbetapir, 18 F-labeled florbetaben, or 18 F-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 (PM 2.5 ) and ground-level ozone (O 3 ) 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. RESULTSThe 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 PM 2.5 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/m 3 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/m 3 increase in PM 2.5 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 O 3 concentrations was not associated with amyl...

Neuroinflammatory and neurometabolic consequences from inhaled 2020 California wildfire smoke-derived particulate matter at a remote location

“…The recent spate of wildfires around the globe have provoked concern that smoke exposures may promote vascular and, by extension, neurological consequences 35,36 . While clear relationships between ambient air pollutants, such as PM2.5 and carbon monoxide, and increased incidence of ADRD have been reported 7,8,9 , there have been no specific assessments of wildfire smoke PM impacts on neuroinflammation or markers of ADRD. Findings of the present study confirm that the WFS-derived PM2.5 traveling from distant wildfires can promote numerous outcomes consistent with ADRD pathogenesis and neurological aging.…”

“…Short-and long-term pulmonary, cardiovascular, and neurological outcomes from inhaled ambient PM are well studied; however, relatively little is known about the impact of WFS-derived PM on neurological outcomes -including implications for priming agerelated disease sequelae. Ambient PM2.5 (PM less than 2.5 microns in aerodynamic diameter) has been associated with increased incidence of Alzheimer's disease and related disorders (ADRD), suicide, depression, psychosis, and other adverse neurological outcomes 7,8,9,10 . Impairment of blood brain barrier (BBB) and neuroinflammation has been implicated in pathophysiology of these neurological disorders.…”

Activation of Endogenous Retrovirus, Brain Infections and Environmental Insults in Neurodegeneration and Alzheimer’s Disease

“…In fact, pollutants can induce many neuro-pathological alterations and affect brain functioning. A recent report indicates that in a 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 [ 82 ].…”

“…Moreover, higher particulate (PM 2.5 ) air levels appeared to be associated with brain amyloid-β plaques, one neuropathological hallmark of AD [ 82 ]. Therefore, exposure to air pollution is associated with amyloid-β pathology in older adults and increases the risk of cognitive impairment and AD.…”

Long-term air pollution exposure and incident dementia in American elderly population: a national cohort study (2000-2018)

“…A cohort study conducted in Ontario, Canada by 22 simultaneously accessed the effects of PM2.5, NO2, and O3 on dementia risks, and they also found significant associations with PM2.5 and NO2, but not O3. Recent 2018 and 2020 Lancet Commission overviews of modifiable environmental agents associated with disease noted a possible association between air pollutants and dementia, but noted the evidence still preliminary 1,23 .The epidemiologic findings are supported by brain imaging and toxicologic studies.Regarding brain imaging, Shaffer et al (2021)24 have found associations between PM2.5 and AD neuropathology upon autopsy, while Laccarino et al (2020)25 found an association between PM2.5 and positive positron emission tomography (PET) scans for amyloid. Younan et al…”