APOE-ε4 Alleles Modify the Decline of MMSE Scores Associated With Time-Dependent PM_2.5 Exposure: Findings From a Community-Based Longitudinal Cohort Study

Objective: Limited research has explored the long-term effect of reduced PM_2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM_2.5 exposure and the interactions of PM_2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele. Methods: Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM_2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM_2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles. Results: After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM_2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM_2.5 decreased over time, the impact of PM_2.5 on MMSE decline also slowly diminished. Conclusion: Long-term PM_2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM_2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools.