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

Abstract

INTRODUCTION

Our understanding of how fine particulate matter (PM_2.5) 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 PM_2.5 exposure on cognitive processing time (CPT), using the change in white blood cell (WBC) count and its subtypes as potential mediators.

RESULTS

Heightened PM_2.5 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 PM_2.5 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 (PM_2.5) 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 PM_2.5 on cognitive functioning.
• Monocyte count played a crucial role in this low-pollution setting.
• Systemic inflammation may contribute to the neurotoxic effects of PM_2.5.