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Publication Detail
Sequences of cognitive decline in typical Alzheimer's disease and posterior cortical atrophy estimated using a novel event-based model of disease progression.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Firth NC, Primativo S, Brotherhood E, Young AL, Yong KXX, Crutch SJ, Alexander DC, Oxtoby NP
  • Publication date:
    02/06/2020
  • Journal:
    Alzheimers Dement
  • Status:
    Published
  • Country:
    United States
  • Language:
    eng
  • Keywords:
    Alzheimer's disease, ceiling, cognitive decline, dementia, disease progression model, effect, floor, kernel density estimate, non-Gaussian, nonparametric mixture model, posterior cortical atrophy
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) ( 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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