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

Content Provider	Europe PMC
Author	Firth, Nicholas C. Primativo, Silvia Brotherhood, Emilie Young, Alexandra L. Yong, Keir X.X. Crutch, Sebastian J. Alexander, Daniel C. Oxtoby, Neil P.
Abstract	AbstractIntroductionThis work aims to characterize the sequence in which cognitive deficits appear in two dementia syndromes.MethodsEvent‐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.ResultsExperiments 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.DiscussionOur 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.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8432168&blobtype=pdf
Page Count	9
ISSN	15525260
Journal	Alzheimer's & Dementia [Alzheimers Dement]
Volume Number	16
DOI	10.1002/alz.12083
PubMed Central reference number	PMC8432168
Issue Number	7
PubMed reference number	32489019
e-ISSN	15525279
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2020-06-02
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Subject Keyword	Alzheimer's disease ceiling cognitive decline dementia disease progression model effect floor kernel density estimate non‐Gaussian nonparametric mixture model posterior cortical atrophy
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Cellular and Molecular Neuroscience Epidemiology Health Policy Psychiatry and Mental Health Geriatrics and Gerontology Developmental Neuroscience