Characterizing the effects of sex, APOE 4, and literacy on mid-life cognitive trajectories: Application of Information-Theoretic model-averaging and multi-model inference techniques to the Wisconsin Registry for Alzheimer’s Prevention Study

Abstract

In this paper we apply Information-Theoretic (IT) model averaging to characterize a set of complex interactions in a longitudinal study on cognitive decline. Prior research has identified numerous genetic (including sex), education, health and lifestyle factors that predict abnormal cognitive decline.Traditional model selection approaches (e.g., backward or stepwise selection), attempt to find models that best fit the observed data; these techniques risk interpretations that only the selected predictors are important. In reality, several models may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates), and inference from a single model chosen after a selection procedure can lead to overly simplistic conclusions. Here we utilize longitudinal cognitive data from the Wisconsin Registry for Alzheimers Prevention to examine the effects of sex and the Apolipoprotein E (APOE) 4 allele (non-modifiable factors), and reading literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a model set with combinations of interactions among sex, APOE, literacy, and age. For a list-learning test, model-averaged results showed better performance for women vs men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less effect in this age range (~40-70). These results illustrate the utility of the IT approach and point to verbal ability as a potential modifier of decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work.