Urinary nickel and risk of all-cause and neurological mortality in Chinese older adults: Evidence from a prospective cohort study

Nickel exposure may increase the risk of adverse health outcome, but population-based data linking it to mortality in older adults are inconsistent and limited, especially neurological mortality. We enrolled 9727 adults aged 60 years and older from two cohorts. Urinary nickel levels were quantified via inductively coupled plasma mass spectrometry (ICP-MS). Participants (enrolled 2017/2018) were followed until death or December 31, 2024. The Kaplan-Meier (KM) method was used to analyze survival associations between urinary nickel and mortality. Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Restricted cubic splines (RCS) were used to assess dose-response relationships, and subgroup analyses were performed to identify susceptible populations and potential effect modifiers. Over 4.75 years (mean follow-up), 2740 deaths (28.7%) occurred (1344 cardiovascular, 288 cancer, 312 respiratory, 163 neurological). A positive association was observed between higher urinary nickel levels and elevated risks of all-cause mortality (2.0% 0.8%-3.2% per 1 μg/L increase) and neurological mortality (12.3% 8.4%-16.3%). Dose-response analyses revealed a nonlinear inverted J-shaped pattern for all-cause and a non-monotonic upward pattern for neurological mortality. Subgroup analyses identified the oldest-old, women, and Han Chinese individuals as particularly susceptible to all-cause mortality, while neurological mortality risks were elevated across sexes, with the oldest-old and Han Chinese at higher risk. Refined neurological mortality analysis confirmed that each 1 μg/L increase in urinary nickel was significantly associated with higher mortality risks from AD (HR = 1.164, 95% CI: 1.029-1.316), other neurodegenerative diseases (NDD; HR = 1.120, 95% CI: 1.078-1.164), and non-NDD neurological diseases (HR = 1.135, 95% CI: 1.014-1.271). In conclusion, higher urinary nickel levels were associated with increased all-cause and neurological mortality, supporting nickel's role as a neurotoxicant. These findings demonstrate the public health risks of nickel exposure in aging populations, necessitating targeted interventions to reduce exposure in vulnerable groups.