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: The data surrounding selenium and selenoproteins and the associations with cognition are controversial with some studies suggesting neurotoxic properties of selenoproteins. However, the literature weighs more towards selenium having potential safeguarding properties against cognitive decline, at least in those with lower baseline biomarker concentrations,through its role in protecting DNA, proteins and lipids in the brain from oxidative damage.
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 over 5 years of follow-up.
Methods: Global cognitive performance was assessed in 757 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 tertiles of selenium status biomarkers and cognitive function (global and attention-specific) at baseline. Linear mixed models explored associations between selenium status tertiles and cognitive decline prospectively over 5 years for global cognition and 3 years for attention-specific cognition.
Results: At baseline, in fully adjusted models, higher serum selenium was associated with better scores in SMMSE (β 0.32±0.14, P=0.02) and sustained focus (β -41.34±36.91, P=0.03). SELENOP and GPx3 activity were not associated with any cognitive outcomes. Over 3 and 5 years, none of the selenium biomarkers were associated with the rate of cognitive decline.
Conclusions: Serum selenium, but not SELENOP or GPx3 activity, was associated non-linearly with global cognition at baseline. These associations were not evident during follow-up. This may be due to the inevitable attrition during follow-up, insufficient follow-up duration to detect cognitive changes, or the sensitivity of the cognitive measurements to detect subtle changes in cognition.