Building Prediction Models for Dementia: The Need to Account for Interval Censoring and the Competing Risk of Death

Abstract

Context. Prediction models for dementia are crucial for informing clinical decision making in older adults. Previous models have used genotype and age to obtain risk scores to determine risk of Alzheimer’s Disease, one of the most common forms of dementia (Desikan et al., 2017). However, previous prediction models do not account for the fact that the time to dementia onset is unknown, lying between the last negative and the first positive dementia diagnosis time (interval censoring). Instead, these models use time to diagnosis, which is greater than or equal to the true dementia onset time. Furthermore, these models do not account for the competing risk of death which is quite frequent among elder adults. Objectives. To develop a prediction model for dementia that accounts for interval censoring and the competing risk of death. To compare the predictions from this model with the predictions from a naïve analysis that ignores interval censoring and the competing risk of death. Methods. We apply the semiparametric sieve maximum likelihood (SML) approach to simultaneously model the cumulative incidence function (CIF) of dementia and death while accounting for interval censoring (Bakoyannis, Yu, & Yiannoutsos, 2017). The SML is implemented using the R package intccr. The CIF curves of dementia are compared for the SML and the naïve approach using a dataset from the Indianapolis Ibadan Dementia Project. Results. The CIF from the SML and the naïve approach illustrated that for healthier individuals at baseline, the naïve approach underestimated the incidence of dementia compared to the SML, as a result of interval censoring. Individuals with a poorer health condition at baseline have a CIF that appears to be overestimated in the naïve approach. This is due to older individuals with poor health conditions having an elevated risk of death. Conclusions. The SML method that accounts for the competing risk of death along with interval censoring should be used for fitting prediction/prognostic models of dementia to inform clinical decision making in older adults. Without controlling for the competing risk of death and interval censoring, the current models can provide invalid predictions of the CIF of dementia.