The Association Between Selenium Status and Global and Attention Specific Cognition in Very Old Adults in the Newcastle 85+ Study: Cross-Sectional and Longitudinal Analyses

Background Selenium has potential safeguarding properties against cognitive decline, due to its role in protecting DNA, proteins, and lipids in the brain from oxidative damage. However, acute and chronic overexposure to selenium can be neurotoxic. Objective The aim of this analysis was to explore the association between selenium status (serum selenium and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity) and cognitive function in 85-year-olds living in Northeast England at baseline and up to 5 years of follow-up. Methods Global cognitive performance was assessed in 755 participants from the Newcastle 85+ study using the Standardized Mini-Mental State Examination (SMMSE) and attention-specific cognition was assessed using composite scores derived from the Cognitive Drug Research (CDR) System. Serum selenium, SELENOP and GPx3 activity were measured at baseline by total reflection X-ray fluorescence (TXRF), ELISA and coupled-enzyme reaction, respectively. Regression analyses explored linear and non-linear associations between continuous values and tertiles of selenium status biomarkers, respectively, and cognitive function at baseline. Generalized linear mixed models explored associations between continuous values and tertiles of selenium status biomarkers, and global cognitive decline over 5 years, and attention-specific cognitive decline over 3 years. Results Over 3 and 5 years, none of the selenium biomarkers were associated with the rate of cognitive decline. At baseline, in fully adjusted models, higher serum selenium was non-linearly associated with global cognition (β 0.05±0.01, P=0.387 linear, β 0.04±0.01, P=0.002 non-linear). SELENOP and GPx3 activity were not associated with any cognitive outcomes. Conclusions There were no associations between selenium status and cognitive decline. However, serum selenium, but not SELENOP or GPx3 activity, was positively associated non-linearly with global cognition at baseline. Furthermore, these associations were not evident during follow-up, potentially due to residual confounding and reverse causation.