Air pollution in relation to brain health indicators and global cognitive functioning in people with cardiovascular disorders along the heart-brain axis

• We examined associations of air pollution with global cognitive functioning. • We did this in reference participants and various heart-brain axis patient groups. • No significant associations of PM2.5, PM10 and NO 2 with cognition were observed. • Associations were not mediated by MRI-derived white matter hyperintensities. • Associations were also not mediated by total brain volume and cerebral blood flow. . There is increasing evidence of an inverse relationship between air pollution and cognitive functioning. Yet, the biological mechanisms underlying this relationship remain underexplored in healthy and vulnerable populations. This study examined cross-sectional and longitudinal associations between air pollution and global cognitive functioning in individuals without or with heart failure, carotid occlusive disease, or vascular cognitive impairment. We also assessed whether the cross-sectional associations were mediated by white matter hyperintensities (WMH), total brain volume (TBV), and cerebral blood flow (CBF). The cross-sectional and longitudinal analyses included data from 341 and 180 Heart-Brain Study participants, respectively. Cognitive functioning was measured using neuropsychological tests at baseline and two-year follow-up. Brain Magnetic Resonance Imaging provided WMH and TBV in mL, and CBF in mL/100g/min. WMH and TBV were divided by total intracranial volume. Annual average outdoor concentrations of particulate matter with diameters <2.5µm and <10.0µm, and nitrogen dioxide in µg/m 3 in residential six-digit postal code areas were linked to participants at baseline. Adjusted multi-level regression analyses showed no significant cross-sectional or longitudinal associations between air pollution and global cognitive functioning. The associations between air pollutants and global cognitive functioning were not significantly mediated by WMH, TBV, and CBF. In this study, air pollution was not associated with global cognitive functioning or brain health indicators in healthy individuals and those with cardiovascular disorders along the heart-brain axis. Larger studies with longer follow-up periods are warranted to extend the present findings and to further elucidate potential associations between air pollution, cognition, and the underlying biological mechanisms.