Cadmium exposure and cognitive impairment in middle-aged and older adults: Linking neurocognitive deficits with...

Cadmium is a widespread environmental toxin, with accumulating evidence implicating its role in neurodegenerative processes; however, its relationship with cognitive impairment and systemic inflammation in humans remains unclear. In this cross-sectional study, 132 middle-aged and older adults were categorized into low (LUCd, ≤5 μg/g creatinine) and high (HUCd, >5 μg/g creatinine) urinary cadmium groups. Cognitive function was comprehensively assessed using the MATRICS Consensus Cognitive Battery (MCCB). Urinary cadmium levels were quantified by inductively coupled plasma mass spectrometry (ICP-MS), and peripheral inflammatory markers were measured from blood samples. Participants in the HUCd group showed significantly lower scores across multiple MCCB domains, including verbal learning, working memory, and overall cognition, compared with those in the LUCd group. Urinary cadmium levels were linearly associated with poorer word memory performance. The HUCd group also exhibited higher levels of systemic inflammation indices, including the systemic immune-inflammation index (SII), systemic immune regulation index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), along with a reduced lymphocyte-to-monocyte ratio (LMR). Logistic regression identified urinary cadmium and SIRI as independent predictors for multidomain cognitive impairment. Receiver operating characteristic (ROC) analyses yielded optimal cut-off ranges for UCd (3.85-5.75 μg/g creatinine) and inflammatory markers (SIRI 0.50-0.54; NLR 1.48-1.72; MLR 0.16; SII 365.07; NE% 57.75-58.72). This study provides the first integrated evidence linking high environmental cadmium exposure to cognitive decline and systemic inflammation in humans. Elevated urinary cadmium and inflammatory indices such as SIRI and NLR may serve as early biomarkers of cadmium-related cognitive vulnerability, offering potential novel avenues for early detection, prevention, and intervention.