Heterogeneous patterns of cognitive decline in Alzheimer's disease across three domains of cognition

Background Others have examined heterogeneity in Alzheimer's disease (AD); however, few have used longitudinal data while accounting for variation in disease stage. We used latent classes to model heterogeneity in the trajectories of three cognitive domains (memory, language, and executive functioning) starting at AD dementia diagnosis. Objective Our aim was to describe the patterns of heterogeneity in cognitive decline across cognitive domains during the course of AD and to contextualize our findings by assessing associations with demographic factors and neuropathological measures. Methods We used cognitive data from the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study in a multi-dimensional joint latent class mixed model, which allowed us to estimate cognitive trajectories that varied across cognitive domains and latent classes. We accounted for the uncertainty in latent class assignment and corrected for multiple hypotheses when assessing the association of the latent classes with demographic and neuropathological variables. Results We identified five latent classes differentiated by level of impairment (high to low) and rate of decline (slow to fast). Within each latent class, the pattern of decline did not differ substantially across cognitive domains. Classes were associated with APOE genotype, sex, race, education, and neuritic plaque and neurofibrillary tangle burden. Conclusions Our results highlight global differences in the level of cognitive impairment at diagnosis and the rate of decline rather than differences between domains of cognition. Examination of patterns in the global rate of cognitive decline may improve understanding of heterogeneity in AD.