Global dynamics of blood cadmium in older adults and its association with Alzheimer’s disease mortality: A Bayesian hierarchical model-based analysis of 30 countries from 1990 to 2020

Cadmium (Cd), a ubiquitous environmental pollutant, exhibits potential neurotoxic risk. While compelling evidence links Cd accumulation to the pathogenesis of Alzheimer's disease (AD), the global impact of blood Cd exposure on AD mortality remains underexplored. We conducted an extensive review of 102 studies from 30 countries and standardized blood Cd concentrations to estimate the geometric mean (GM) and geometric standard deviation (GSD) of Cd exposure. Estimated annual percentage change (EAPC) was calculated to assess the trend in AD mortality, with 1000 Monte Carlo simulations to estimate population attributable fractions (RAF). The augmented human development index (AHDI) was used to analyze correlations with Cd-related mortality. Bayesian hierarchical regression models revealed a 72% reduction in GM in Egypt, contrasted by a 142% increase in Australia. Germany and Brazil demonstrated significant GM reductions along with increased GSD, reflecting regional variability. Conversely, Japan and South Korea exhibited marked rises in the regional variability, while Egypt and France achieved significant reductions in Cd-related AD deaths for both males and females, reaching zero by 2020. The number of deaths related to Cd in Australia and Japan has increased. While countries like Norway, Germany, and Lithuania showed declining mortality trends, others (e.g., Poland and Italy), exhibited rising mortality despite AHDI improvements. This study represents the first comprehensive assessment of the global burden of AD attributable to blood Cd exposure, reveal significant regional disparities. It provides epidemiological references for policymakers to formulate Cd management strategies and guides researchers in selecting impactful study directions.