Observational Cohorts Link PM2.5 and NO2 to Opposing Cortical Thickness Patterns in Alzheimer's-Vulnerable Regions by Age and Sex

The NeuroToxicology cross-sectional analysis combined structural MRI with residential air-pollution modeling from the Women's Health Initiative Memory Study (1,097 women) and the Vietnam Era Twin Study of Aging (387 men). Cortical thickness in four Alzheimer's-vulnerable regions served as the primary outcome; each 1 µg/m³ increase in PM2.5 corresponded to roughly 13 months of additional aging-related thinning among the older women, while the younger men showed the opposite direction that attenuated with advancing age.

These divergent patterns align with prior longitudinal data from the same WHIMS cohort showing PM2.5-associated cognitive decline and with European registry studies linking traffic-related NO2 to incident dementia. The reversal around age 65 may reflect an early compensatory phase followed by accelerated neurodegeneration, yet the design cannot separate age, sex, or unmeasured confounders such as socioeconomic status or vascular risk.

Next steps require serial imaging and incident Alzheimer's adjudication within these cohorts to test whether the observed thickness differences predict clinical progression by 2030. Replication in demographically balanced samples is also needed before any exposure-reduction guidance can be issued.