Urinary phthalate exposure in relation to plasma neurofilament light chain and cognitive function among older adults: Repeated-measures and cross-sectional analyses.

Abstract

Phthalates (PAEs) are ubiquitous neurotoxic contaminants, but their effects on cognitive function in the elderly remain unclear. In this study, we explored the associations between repeated urinary PAE measurements and plasma neurofilament light chain (NfL) levels, as well as cognitive function among older adults in Shanghai. Ten urinary PAE metabolites were measured in 330 participants in 2019, 2021, and 2023. Plasma NfL was measured and the Mini-Mental State Examination (MMSE) was administered during the third survey wave. A complementary cross-sectional analysis included 1020 participants assessed in 2023. Both single-pollutant and mixture models were applied. In the repeated-measures analysis, the 2021 PAE mixture (β = 0.071; 95% CI: 0.005, 0.138) and the joint mixture across all three waves (β = 0.096; 95% CI: 0.003, 0.189) were associated with higher NfL levels. No significant associations with MMSE outcomes were observed in the smaller cognitive subsample. In the 2023 analysis, the PAE mixture was associated with higher NfL levels, lower orientation, registration, and total MMSE scores, and higher odds of cognitive impairment. These findings suggest that the associations with NfL may vary according to the timing of exposure assessment and provide complementary cross-sectional evidence linking PAE exposure to selected cognitive outcomes. Further prospective studies are needed to confirm these findings.