Application of joint model in characterizing pre- and post-dementia trajectory of cognitive function

The e4 allele of the Apolipoprotein E (APOE) is well-recognized as a strong risk factor for incidence of dementia. However, there have been conflicting results on the effect of the allele on cognitive function after dementia onset. As the allele is also implicated in other diseases related to early mortality, there may exist a survival bias impacting the performance of a traditional mixed effects model. Therefore, we propose the use of joint modeling to examine whether the association between APOE e4 and cognitive function is changed before and after dementia onset. Here, we define cognitive function using multiple longitudinal outcomes measuring four cognitive domains of memory, attention, executive function, and language. We use a multivariate joint model with a time to death outcome, and draw a comparison to univariate joint models . We use as a motivating example data from the National Alzheimer’s Coordinating Center.