Sequences Of Cognitive Decline In Typical Alzheimer'S Disease And Posterior Cortical Atrophy Estimated Using A Novel Even Based Model Of Disease Progression
ALZHEIMERS & DEMENTIA(2020)
摘要
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) (n = 94) and typical Alzheimer's disease (tAD) ( n = 61) 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.
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关键词
Alzheimer's disease, ceiling, cognitive decline, dementia, disease progression model, effect, floor, kernel density estimate, non-Gaussian, nonparametric mixture model, posterior cortical atrophy
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