causal mediation analysis; cognitive functioning; fine particulate matter; leukocytes; systemic inflammation; white blood cell count; Particulate Matter; Air Pollutants; Humans; Male; Female; Prospective Studies; Middle Aged; Netherlands/epidemiology; Adult; Aged; Inflammation; Leukocyte Count; Air Pollution/adverse effects; Air Pollution/statistics & numerical data; Cohort Studies; Air Pollutants/adverse effects; Particulate Matter/adverse effects; Cognitive Dysfunction; Mediation Analysis; Leukocytes/drug effects; Environmental Exposure/adverse effects; Air Pollution; Environmental Exposure; Netherlands; Epidemiology; Health Policy; Developmental Neuroscience; Neurology (clinical); Geriatrics and Gerontology; Cellular and Molecular Neuroscience; Psychiatry and Mental Health
Abstract :
[en] [en] INTRODUCTION: Our understanding of how fine particulate matter (PM2.5) impacts cognitive functioning is limited. Systemic inflammation processes may play a role in mediating this effect.
METHODS: This prospective cohort study used data from 66,254 participants aged 18+ between 2006 and 2015 from the Dutch Lifelines Cohort Study and Biobank. Causal mediation analysis was conducted to examine the impact of ambient PM2.5 exposure on cognitive processing time (CPT), using the change in white blood cell (WBC) count and its subtypes as potential mediators.
RESULTS: Heightened PM2.5 exposure was associated with slower CPT (total effect = 81.76 × 10-3, 95% confidence interval [CI] 59.51 × 10-3-105.31 × 10-3). The effect was partially mediated via increased WBC count (indirect effect [IE] = 0.42 × 10-3, 95% CI 0.07 × 10-3-0.90 × 10-3), particularly driven by an increase in monocytes (IE = 0.73 × 10-3, 95% CI 0.24 × 10-3-1.31 × 10-3).
DISCUSSION: Systemic inflammation processes may partially explain the harmful effects of PM2.5 on cognitive functioning, why lower levels of systemic inflammation may help contain its neurotoxic effects.
HIGHLIGHTS: The pathways leading to the neurotoxic effects of fine particulate matter (PM2.5) are poorly understood. We analyzed data from over 66,000 participants using causal pathway analysis. Increased white blood cell (WBC) count mediates the effect of PM2.5 on cognitive functioning. Monocyte count played a crucial role in this low-pollution setting. Systemic inflammation may contribute to the neurotoxic effects of PM2.5.
Disciplines :
Neurology
Author, co-author :
Aretz, Benjamin ; Institute of Sociology and Demography, University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany ; Institute of General Practice and Family Medicine, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany
Doblhammer, Gabriele ; Institute of Sociology and Demography, University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany ; German Center for Neurodegenerative Diseases(DZNE), Demographic Studies, Bonn, Germany
HENEKA, Michael ; University of Luxembourg ; Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
External co-authors :
yes
Language :
English
Title :
The role of leukocytes in cognitive impairment due to long-term exposure to fine particulate matter: A large population-based mediation analysis.
Publication date :
December 2024
Journal title :
Alzheimer's and Dementia: the Journal of the Alzheimer's Association
We thank Lifelines for providing the data and their support. The Lifelines Biobank initiative was made possible by a subsidy from the Dutch Ministry of Health, Welfare, and Sport; the Dutch Ministry of Economic Affairs; the University Medical Center Groningen (UMCG the Netherlands), University Groningen; and the Northern Provinces of the Netherlands. We further thank the Cogstate Research Team for their support in handling the data coming from the Cogstate Brief Battery. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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