Aromatic amine antioxidants (AAs) and p-phenylenediamine quinones (PPD-Qs) exposure, thyroid hormones, and cognitive function in older adults: Association and potential mediation analyses.

Aromatic amine antioxidants (AAs) and p-phenylenediamine quinones (PPD-Qs) are novel environmental contaminants derived from tire wear, with emerging neurotoxic concerns, but epidemiological evidence linking them to cognitive health is lacking. This study investigated associations between exposure to these chemicalsand cognitive performance in older adults, and explored the potential mediating role of thyroid hormones. We measured urinary concentrations of nineteen AAs and six PPD-Qs in 439 older adults from Shenzhen, China, and assessed cognitive function using the Mini-Mental State Examination (MMSE). Higher urinary levels of specific compounds, such as N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), 4-(cyclohexylamino) diphenylamine-quinone (CPPD-Q), and 4-phenylaminodiphenylamine-quinone (DPPD-Q), were significantly associated with lower MMSE scores and increased risks of cognitive impairment. Mixture analyses further indicated that combined exposure to these chemicals was linked to poorer cognitive performance, with 6PPD-Q and CPPD-Q as the most significant contributors. Additionally, specific thyroid hormones were associated with both chemical exposures and cognitive outcomes. Exploratory mediation analysis suggested that thyrotropin (TSH) and total triiodothyronine (TT3) may mediate the association between DPPD-Q exposure and poorer performance in specific cognitive domains. These findings provide the first epidemiological evidence that AAs and PPD-Qs exposure may be associated with cognitive decline in the elderly, potentially via disruption of thyroid hormone homeostasis. These observations warrant confirmation in longitudinal studies.