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
, 16
(7)
pp. 965-973.
10.1002/alz.12083.
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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 > 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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