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

Firth, NC; Primativo, S; Brotherhood, E; Young, AL; Yong, KXX; Crutch, SJ; Alexander, DC; (2020) Sequences of cognitive decline in typical Alzheimer's disease and posterior cortical atrophy estimated using a novel event‐based model of disease progression. Alzheimer's & Dementia 10.1002/alz.12083. (In press). Green open access

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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.

Type: Article
Title: Sequences of cognitive decline in typical Alzheimer's disease and posterior cortical atrophy estimated using a novel event‐based model of disease progression
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/alz.12083
Publisher version: https://doi.org/10.1002/alz.12083
Language: English
Additional information: Copyright © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Alzheimer's disease, ceiling, cognitive decline, dementia, disease progression model, effect, floor, kernel density estimate, non-Gaussian, nonparametric mixture model, posterior cortical atrophy
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10100204
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