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Retinal imaging for the early diagnosis of Alzheimer's disease

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posted on 2022-11-18, 05:39 authored by Isaiah-Lorenzo De Guia

Alzheimer’s disease (AD) is disabling, and current early diagnostic methods are clinically inaccessible. Imaging the retina to investigate brain health in AD for early diagnosis is promising yet, challenging in identifying amyloid-beta (Aβ, a hallmark feature found in AD brain) in the live human retina. Circadian activity such as the sleep/rest cycle is linked to the retina and therefore, surrogate information such as sleep disruption may be useful additions for achieving predictive diagnosis. 

As part of the updated study aims due to the coronavirus disease 2019 (COVID-19) restrictions in New South Wales (June 2021-December 2021), quality assessment was performed for 165 raw hyperspectral retinal images and images rated based on an inhouse developed image rating scale. Following quality assessment, identification of retinal deposits of interest occurred in 45 images within the spectral range of 450-790 nm. 

Findings from the study’s first narrative review indicates that from a novel diagnostic perspective, sleep-wake cycle disruption in AD could be due to the deposition of Aβ around the melanopsin retinal ganglion cells responsible for sleep-wake cycle. Thus, sleep disruption may indicate retinal damage in AD. Findings from the study’s second narrative review provides clinical evidence for an interplay between COVID-19, dementia and TDP-43 as drivers of neurodegeneration. 

Overall, this is the first study to show various artefacts and identified deposits of interest in raw hyperspectral images. Further investigation is required to determine whether retinal deposits of interest have any diagnostic significance. Moreover, the potential utility of retinal imaging measures combined with sleep/chronobiological information as surrogate markers may aid in retinal imaging trials for the early diagnosis of AD. More studies are needed to identify mixed or overlapping pathologies due to COVID-19, AD and/or TDP-43 proteinopathy to investigate disease specific, signature mechanisms of action to assist in clinical decision making and informed management strategies.


Table of Contents

Chapter 1 - Introduction/literature review -- Chapter 2 - Methods -- Chapter 3 - Raw hyperspectral retinal images show deposits of interest after performing image quality assessment -- Chapter 4 - The crosstalk between amyloid-beta, retina, and sleep for the early diagnosis of Alzheimer's disease: a narrative review -- Chapter 5 - Retinal and brain manifestations of COVID-19 and its associations with dementia, TDP-43 proteinopathy: a narrative review -- Chapter 6 – General discussion and future directions -- Appendix -- References


Presented for the degree of Master of Research

Awarding Institution

Macquarie University

Degree Type

Thesis MRes


Thesis MRes, Macquarie University, Department of Biomedical Sciences, 2022

Department, Centre or School

Department of Biomedical Sciences

Year of Award


Principal Supervisor

Tejal M. Shah

Additional Supervisor 1

Ralph N. Martins


Copyright: The Author Copyright disclaimer:




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