The role of leukocytes in cognitive impairment due to long-term exposure to fine particulate matter: A large population-based mediation analysis.

INTRODUCTION: Our understanding of how fine particulate matter (PM) 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 PM exposure on cognitive processing time (CPT), using the change in white blood cell (WBC) count and its subtypes as potential mediators.

RESULTS: Heightened PM exposure was associated with slower CPT (total effect = 81.76 × 10, 95% confidence interval [CI] 59.51 × 10-105.31 × 10). The effect was partially mediated via increased WBC count (indirect effect [IE] = 0.42 × 10, 95% CI 0.07 × 10-0.90 × 10), particularly driven by an increase in monocytes (IE = 0.73 × 10, 95% CI 0.24 × 10-1.31 × 10).

DISCUSSION: Systemic inflammation processes may partially explain the harmful effects of PM 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 (PM) 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 PM on cognitive functioning. Monocyte count played a crucial role in this low-pollution setting. Systemic inflammation may contribute to the neurotoxic effects of PM.

© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PMID: 39412000