Ambient Air Pollution Exposure Influences Dementia through the Bidirectional Pathways of Psychological Factors and Brain Structure

ABSTRACT: Exposure to air pollution contributes to increased dementia risk, which may be mediated through its impact on psychological and brain structural changes. However, the underlying mechanisms remain poorly understood. We analyzed data from the UK Biobank of 263,095 participants aged 40 years and older. We examined the association between air pollution and incident dementia using Cox proportional hazard regression models. Mediation analysis was performed to explore the mediating roles of psychological and brain structural factors on these associations. Structural equation model (SEM) and bidirectional Mendelian randomization (MR) analyses were further employed to explore the potential pathways involving psychological factors and brain structure in this relationship. During an over 13-year follow-up, a total of 3039 dementia cases were identified. We observed significant associations between air pollution and dementia, with each interquartile range (IQR) increase in air pollution associated with a 5~9% increased risk of dementia. We observed that both psychological and brain structural factors mediated the air pollution-dementia association, particularly loneliness, social isolation, lack of enthusiasm, and reductions in volumes of the amygdala, hippocampus, temporal pole, and frontal pole, with mediation proportions ranging from 4.23% to 11.11%. SEM and MR analyses revealed bidirectional pathways linking air pollution exposure to dementia through psychological factors and brain structural changes: (1) air pollution → psychological disturbances → brain structural damage → dementia; (2) air pollution → brain structural damage → psychiatric disorders → dementia. These findings elucidate the interplay between psychological well-being and neuroanatomical integrity in mediating the neurocognitive impacts of air pollution, offering insights for targeted interventions to mitigate dementia risk associated with environmental exposures.