title: Exposure to air pollution as a potential contributor to cognitive function, cognitive decline, brain imaging, and dementia: A systematic review of epidemiologic research.
abstract: Dementia is a devastating condition typically preceded by a long prodromal phase characterized by accumulation of neuropathology and accelerated cognitive decline. A growing number of epidemiologic studies have explored the relation between air pollution exposure and dementia-related outcomes.
  
  
  
  We undertook a systematic review, including quality assessment, to interpret the collective findings and describe methodological challenges that may limit study validity. Articles, which were identified according to a registered protocol, had to quantify the association of an air pollution exposure with cognitive function, cognitive decline, a dementia-related neuroimaging feature, or dementia.
  
  
  
  We identified 18 eligible published articles. The quality of most studies was adequate to exemplary. Almost all reported an adverse association between at least one pollutant and one dementia-related outcome. However, relatively few studies considered outcomes that provide the strongest evidence for a causal effect, such as within-person cognitive or pathologic changes. Reassuringly, differential selection would likely bias toward a protective association in most studies, making it unlikely to account for observed adverse associations. Likewise, using a formal sensitivity analysis, we found that unmeasured confounding is also unlikely to explain reported adverse associations.
  
  
  
  We also identified several common challenges. First, most studies of incident dementia identified cases from health system records. As dementia in the community is underdiagnosed, this could generate either non-differential or differential misclassification bias. Second, almost all studies used recent air pollution exposures as surrogate measures of long-term exposure. Although this approach may be reasonable if the measured and etiologic exposure windows are separated by a few years, its validity is unknown over longer intervals. Third, comparing the magnitude of associations may not clearly pinpoint which, if any, pollutants are the probable causal agents, because the degree of exposure misclassification differs across pollutants. The epidemiologic evidence, alongside evidence from other lines of research, provides support for a relation of air pollution exposure to dementia. Future studies with improved design, analysis and reporting would fill key evidentiary gaps and provide a solid foundation for recommendations and possible interventions.
authors.affiliation: Department of Epidemiology and Biostatistics, George Washington University Milken Institute School of Public Health, 950 New Hampshire Avenue NW, Washington, DC 20052, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA. Electronic address: power@gwu.edu.
authors.forename: Melinda C
authors.initials: MC
authors.lastname: Power
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, 1420 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: sadar@umich.edu.
authors.forename: Sara D
authors.initials: SD
authors.lastname: Adar
authors.affiliation: Department of Public Health Sciences, The Pennsylvania State University College of Medicine, 90 Hope Drive, Hershey, PA, 17033, USA. Electronic address: jyanosky@phs.psu.edu.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Yanosky
authors.affiliation: Rush Institute for Healthy Aging, Rush University Medical Center, 1645 W. Jackson Boulevard, Suite 675, Chicago, IL 60612, USA; Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA. Electronic address: jweuve@bu.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Weuve
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D001921:Brain / Q000000981:diagnostic imaging*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology; D003704:Dementia / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology; D016021:Epidemiologic Studies; D006801:Humans
keywords: Air pollution; Alzheimer disease; Cognitive decline; Cognitive function; Dementia; Systematic review