Urinary and Blood Cadmium and Alzheimer’s Disease Mortality in U.S. Adults

Abstract

Introduction: Emerging evidence suggests heavy metals, such as cadmium, may contribute to neurodegenerative disease risk. At least two cross-sectional studies found elevated blood cadmium in Alzheimer’s disease (AD) patients, but whether cadmium is associated with increased Alzheimer’s disease mortality remains unknown. Methods: A subsample of 2,023 participants from the U.S. National Health and Nutrition Examination Survey (NHANES) cycles 1999/2000 through 2005/2006, who were at least 60 years old at baseline, had complete urinary cadmium and covariate data, and known mortality status as of December 31st, 2011 were included in the analysis. Survey-weighted Cox proportional hazard models were used to estimate the association between urinary cadmium or blood cadmium and incident AD deaths as identified on death certificates from the National Death Index. All models were adjusted for age, sex, race/ethnicity and smoking status. Results: During follow-up, 21 AD deaths were recorded (median follow-up: 90 months; IQR: 66, 117). At baseline, those who eventually died of AD had a median urinary cadmium level of 0.58 µg/L (IQR: 0.25, 1.06), while those who remained alive (n=1,387) or died of other causes (n=615) had a median urinary cadmium of 0.43 µg/L (IQR: 0.22, 0.75). An IQR (0.53 µg/L) increase in urinary cadmium was associated with 46% greater (95% CI: 23%, 74%; P<0.0001) AD mortality hazard. Results were similar with further adjustment for urinary creatinine. However, in the subset of participants with blood cadmium measures (n=1,520; AD =16), blood cadmium was not associated with AD mortality (HR per IQR (0.4 µg/L) increase: 1.10 (95% CI: 0.77, 1.56; P=0.6). Conclusions: Urinary cadmium was significantly associated with elevated AD mortality. In a subsample, blood cadmium was not associated with AD mortality. Further studies are warranted to replicate these findings and investigate the timing of cadmium exposure for AD risk.