Traffic-Related Air Pollution and Incident Dementia: Direct and Indirect Pathways Through Metabolic Dysfunction

Article type: Research Article

Authors: Paul, Kimberly C.^{a; *} | Haan, Mary^{b; *} | Yu, Yu^a | Inoue, Kosuke^a | Mayeda, Elizabeth Rose^a | Dang, Kristina^b | Wu, Jun^c | Jerrett, Michael^d | Ritz, Beate^{a; d; *}

Affiliations: [a] Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA | [b] Department of Epidemiology & Biostatistics, UCSF, San Francisco, CA, USA | [c] Program in Public Health, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, Irvine, CA, USA | [d] Department of Environmental Sciences, UCLA Fielding School of Public Health, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Kimberly C. Paul, PhD, Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA. E-mail: kimberlp@ucla.edu; Mary Haan, Dr PH, Department of Epidemiology & Biostatistics, UCSF, San Francisco, CA, USA. E-mail: Mary.Haan@ucsf.edu; Beate Ritz, MD, PhD, Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA 90095-1772, USA. Tel.: +1 310 825 8579; E-mail: britz@ucla.edu.

Abstract: Background:Ambient air pollution exposure has been associated with dementia. Additionally, epidemiologic evidence supports associations between air pollution and diabetes as well as diabetes and dementia. Thus, an indirect pathway between air pollution and dementia may exist through metabolic dysfunction. Objective:To investigate whether local traffic-related air pollution (TRAP) influences incident dementia and cognitive impairment, non-dementia (CIND) in a cohort of older Mexican Americans. We also assess how much of this estimated effect might be mediated through type 2 diabetes (T2DM). Methods:In a 10-year, prospective study of Latinos (n = 1,564), we generated TRAP-NOx as a surrogate for pollution from local traffic sources at participants’ residences during the year prior to enrollment. We used Cox proportional hazards modeling and mediation analysis to estimate the effects of TRAP-NOx on dementia and/or CIND and indirect pathways operating through T2DM. Results:Higher TRAP-NOx was associated with incident dementia (HR = 1.55 for the highest versus lower tertiles, 95% CI = 1.04, 2.55). Higher TRAP-NOx was also associated with T2DM (OR = 1.62, 95% CI = 1.27, 2.05); furthermore, T2DM was associated with dementia (HR = 1.94, 95% CI = 1.42, 2.66). Mediation analysis indicated that 20% of the estimated effect of TRAP-NOx on dementia/CIND was mediated through T2DM. Conclusion:Our results suggest that exposure to local traffic-related air pollution is associated with incident dementia. We also estimated that 20% of this effect is mediated through T2DM. Thus, ambient air pollution might affect brain health via direct damage as well as through indirect pathways related to diabetes and metabolic dysfunction.

Keywords: Air pollution, CALINE4, cognitive decline, dementia, diabetes, Latino, mediation, nitrogen oxide, traffic-related air pollution

DOI: 10.3233/JAD-200320

Journal: Journal of Alzheimer's Disease, vol. 76, no. 4, pp. 1477-1491, 2020