OBJECTIVE: This study explores the relationship between World Trade Center (WTC) response activities (WRAs) and cognitive impairment (CI) and uses a moderated-mediation model to examine the role of wearing a surgical/nuisance dust mask. METHODS: This study includes 3,285 WTC responders. Responders were placed into eight WRA groups based on self-report structured responses and free-text descriptions of activities at the WTC. The presence/absence of surgical/nuisance dust mask usage was self-reported. The outcome was CI as determined using a Montreal Cognitive Assessment score <
23. Robust Poisson regression was used to examine the main effect, and counterfactual moderated-mediation analysis was used to determine the role of mask usage. RESULTS: The risk of CI was higher across most WRAs when compared to supervision. Mask usage was reported by 63% of responders and varied across WRAs and was associated with a reduced risk of CI (adjusted risk ratio [aRR]=0.77, p=0.008) after controlling for WRAs. Moderation effects indicated that responders are more likely to wear masks when encountering more dangerous exposures, even within the same WRA group. Responders in the WRA-enclosed group had a lower risk of CI through a moderated intermediary effect of mask usage (aRR=0.92, p=0.05). CONCLUSION: Surgical/nuisance dust mask usage provided mild protection against air pollution exposures during WTC response activities when compared to not wearing a mask. Results suggest that response workers at disaster sites might benefit from wearing surgical/nuisance dust masks when respirators are unavailable even when the air seems safe.