Sex and APOE Genotype Differences Related to Statin Use in The Aging Population

Abstract Background. Significant evidence suggests that the cholesterol-lowering statins can effect cognitive function, and reduce the risk for Alzheimer’s disease and dementia. These potential effects may be constrained by specific combinations of an individual’s sex and Apolipoprotein E (APOE) genotype. Methods. Here we examine data from 252,327 UK BioBank participants, aged 55 or over, and compare the effects of statin use in males and females. We identified that in this population, males were older, had a higher level of education, better cognitive scores, higher incidence of cardiovascular and metabolic diseases, and a higher rate of statin use.Results. We observed that males and those participants with an APOE4 (E4 variant of APOE) positive genotype had higher probabilities of being treated with statins; while participants with an Alzheimer’s diagnosis had slightly lower probabilities. We found that use of statins was not significantly associated with overall higher rates of survival. However, when considering the interaction of statin use with sex, the results suggest higher survival rates in males treated with statins. Finally, examination of cognitive function indicates a potential beneficial effect of statins, however this is limited to APOE4 positive genotypes. Conclusions. Our evaluation of the ageing population in a large cohort from the UK BioBank confirms sex and APOE genotype as funda mental risk stratifiers for Alzheimer’s disease and cognitive function, furthermore it extends them to the specific area of statin use, clarifying their specific interactions with treatments.