Sequences of cognitive decline in typical Alzheimer's disease and posterior cortical atrophy estimated using a novel event-based model of disease progression

Abstract

Introduction: This work aims to characterize the sequence in which cognitive deficits appear in two dementia syndromes. Methods: Event-based modeling estimated fine-grained sequences of cognitive decline in clinically-diagnosed posterior cortical atrophy (PCA) ((Formula presented.)) and typical Alzheimer's disease (tAD) ((Formula presented.)) at the UCL Dementia Research Centre. Our neuropsychological battery assessed memory, vision, arithmetic, and general cognition. We adapted the event-based model to handle highly non-Gaussian data such as cognitive test scores where ceiling/floor effects are common. Results: Experiments revealed differences and similarities in the fine-grained ordering of cognitive decline in PCA (vision first) and tAD (memory first). Simulation experiments reveal that our new model equals or exceeds performance of the classic event-based model, especially for highly non-Gaussian data. Discussion: Our model recovered realistic, phenotypical progression signatures that may be applied in dementia clinical trials for enrichment, and as a data-driven composite cognitive end-point.