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A proposed theoretical framework for retinal biomarkers

MacCormick, Ian James Callum; Zhang, Bo; Hill, Daniel; Cordeiro, Maria Francesca; Small, Dylan S; (2022) A proposed theoretical framework for retinal biomarkers. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring , 14 (1) , Article e12327. 10.1002/dad2.12327. Green open access

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Abstract

OBJECTIVE: Propose a theoretical framework for retinal biomarkers of Alzheimer's disease (AD). BACKGROUND: The retina and brain share important biological features that are relevant to AD. Developing retinal biomarkers of AD is a strategic priority but as yet none have been validated for clinical use. Part of the reason may be that fundamental inferential assumptions have been overlooked. Failing to recognize these assumptions will disadvantage biomarker discovery and validation, but incorporating them into analyses could facilitate translation. NEW THEORY: The biological assumption that a disease causes analogous effects in the brain and retina can be expressed within a Bayesian network. This allows inferences about abstract theory and individual events, and provides an opportunity to falsify the foundational hypothesis of retina–brain analogy. Graphical representation of the relationships between variables simplifies comparison between studies and facilitates judgements about whether key assumptions are valid given the current state of knowledge. MAJOR CHALLENGES: The framework provides a visual approach to retinal biomarkers and may help to rationalize analysis of future studies. It suggests possible reasons for inconsistent results in existing literature on AD biomarkers. LINKAGE TO OTHER THEORIES: The framework can be modified to describe alternative theories of retinal biomarker biology, such as retrograde degeneration resulting from brain disease, and can incorporate confounding factors such as co-existent glaucoma or macular degeneration. Parallels with analogue confirmation theory and surrogate marker validation suggest strengths and weaknesses of the framework that can be anticipated when developing analysis plans.

Type: Article
Title: A proposed theoretical framework for retinal biomarkers
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/dad2.12327
Publisher version: https://doi.org/10.1002/dad2.12327
Language: English
Additional information: © 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring 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-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Alzheimer's disease, Bayesian, biomarker, brain disease, cerebral malaria, retina, surrogate, validation
UCL classification: 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 > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10152241
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