Understanding the neurocognitive impact of outdoor PM10 and PM2.5 exposure: an in silico dosimetric modeling study using MPPD

Abstract Air pollution has been increasingly linked to adverse neurodevelopmental and neurodegenerative outcomes. While experimental and preclinical studies suggest that exposure to particulate matter (PM), particularly during gestation, may disrupt cognitive development, the impact of short-term PM exposure on cognitive and behavioral functioning in healthy young populations remains insufficiently explored in Spain. Moreover, few studies have incorporated individualized dosimetry models to estimate exposure more accurately. This study included 186 healthy young adults (mean age = 20.4 years) recruited from three Spanish cities (Teruel, Almería, and Talavera) characterized by different pollution levels. Ambient fine and coarse PM concentrations were recorded 8, 15, and 30 days prior to psychological assessment. Instead of relying solely on raw in situ environmental measurements, individualized PM deposition was estimated using the Multiple-Path Particle Dosimetry Model (MPPD), allowing a more biologically meaningful exposure approximation. Psychological outcomes were assessed using validated questionnaires: DASS-21 (depression, anxiety, stress), BIS-11 (impulsivity), UCLA Loneliness Scale, and SWLS (life satisfaction). Behavioral performance was evaluated using computerized versions of the Attentional Network Task (ANT) and the Stroop Task. Blood NRF2 concentrations were analyzed as a biomarker potentially related to oxidative stress mechanisms. In situ data indicated that Talavera presented the highest pollution levels, followed by Almería and Teruel. Linear regression analyses showed that coarse PM exposure across 8-, 15-, and 30-day windows significantly predicted poorer Executive Control Index performance in the ANT. Additionally, 15-day coarse PM and 30-day fine PM exposure were associated with greater cognitive interference. Oxidative stress markers were significantly associated with PM exposure levels. These findings support emerging evidence that short-term PM exposure may negatively affect executive and attentional processes even in healthy young adults. Further longitudinal research incorporating individualized exposure modeling is warranted to clarify causal pathways and underlying biological mechanisms. Graphical Abstract