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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.
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Publication Type:Journal article
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Publication Sub Type:Article
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Authors:Firth NC, Primativo S, Brotherhood E, Young AL, Yong KXX, Crutch SJ, Alexander DC, Oxtoby NP
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Publication date:02/06/2020
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Journal:Alzheimers Dement
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Status:Published
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Country:United States
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Language:eng
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Keywords: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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Author URL:
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Full Text URL:
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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