Multi-modal retinal biomarkers for vascular dementia: developing enabling image analysis tools

Dementia is a devastating disease. It has catastrophic implications for affected individuals, their family, wider society, and heavy, increasing costs for the NHS. Detecting subjects at increased risk of developing dementia in the future, and detecting adverse risk at the earliest stages of dementia, may present opportunities to preserve brain function and delay disease progression.

There is increasing recognition that degeneration of brain blood vessels plays a role in the development of dementia. It is therefore important to identify patients likely to present such degeneration as early as possible, as they may require special treatment and the disease progress can be delayed.

There is also strong clinical evidence that the brain blood vessels are related to those in the retina, the part of the eye responsible for the first stage of human vision. The retina is checked routinely by high-street opticians, hence retinal images (fundus photography and optical coherence tomography, now both available on a single device) could provide an inexpensive, non-invasive procedure capable of capturing early signs of dementia or those at high risk of developing dementia. It would exploit widely available existing examinations and be deployable immediately. Hence the potential impact of a retinal test for dementia signs would be huge.

The central question is whether the retina can provide (a) reliable biomarkers (signs) for future risk of dementia, and (b) sensitive biomarkers of disease progression of either cognitive decline or brain vessels degeneration. Our purpose is to develop enabling technologies based on image analysis to identify such biomarkers, using easily accessible retinal features (supporting an uninvasive, inexpensive, easily accessible and high-specificity test), and joint brain-retina features (a larger-scope investigation motivated by the affinity of small vessels of brain and retina).

We shall validate the technologies in a pilot study in collaboration with the specialist units at the University Hospitals of Dundee and Edinburgh, including ophthalmology, brain imaging, and cognitive ageing and cognitive epidemiology. Our research is supported by the Alzheimer's Society.

== Users and beneficiaries outside academia
These include the NHS (General Practitioners and hospital services) ; opticians; society in general; individual patients and their families through increased availability of a simple screening tool for brain health. Rapid access to early diagnosis of vascular and brain 'health' via an easily accessible test has the potential to improve health and empower the public. Prevention of dementia, and also of stroke
and cognitive impairment is a Government priority and methods to identify subjects at high risk of
future dementia are urgently needed. Preservation of brain has a far better chance of preventing
cognitive decline and dementia than attempting to reverse the dementia after symptom onset.
== Towards societal impact
Dementia is estimated to cost ~£16-20 billion in the UK and rising; caring for affected patients
places an additional drain on carers, and social and health services that is difficult to quantify.
By the time cognition is measurably affected, it may already be too late.
Many dementia assessment tools have focused on Alzheimer's Dementia,
but vascular disease is responsible for up to 45% of dementias and may require tools
sensitive to vascular changes as well as to the effects on the brain structure and cognition.
Our integrated approach to assessing vascular and neural components of the retina and of the brain
offers a superb chance of capturing relevant changes at a time when intervention would have a better chance of working. Keeping even a small proportion of people out of nursing homes or hospital or in work will have a major effect on society as a whole.
== Towards economic impact
Delaying dementia onset by 5 years could reduce costs by half, saving up to £10 billion a year;
but even delaying dementia onset by 1 year could save several billions per year to
society, health services, patients and families individual budgets, and maintain dignity by keeping
people in their own homes. This money could be put into developing better
education, health services, and avoiding the inevitable substantial personal financial losses linked with dementia in a family.
== Public engagement
"Seeing into the brain" from the High Street (retinal imaging by optometrists) has immediate public
resonance and will be an important message to promote. We have wide experience with
public engagement: the Knowledge Transfer Officers of Edinburgh
Neuroscience, Imaging, and in the Centre for Cognitive Ageing and Cognitive
Epidemiology are all very experienced in public engagement; and the dedicated
CCACE knowledge exchange officer will be available to assist the project. He has led, for example, science festival events, schools workshops, collaborations with artists, writers, and playrights, and
led the commercialisation of products for the diagnosis of dementia and delirium.
The Dundee Revealing Research office will assist via public lectures (e.g., the Dundee Saturday Evening Lectures, now in its 90th year), and several other routes.
The Alzheimer Society has offered their support for dissemination, including use of their Annual
Research Conference (see attached letter of support).
== Translation
Translation is the final stage in our 3-part vision: (1) tools development (this project), (2) large-scale trial, (3) translation. Retinal imaging tools developed in this project will
need to undergo extensive testing in independent cohorts and populations to determine their true
applicability (stage 2); both Edinburgh and Dundee undertake large clinical trials and have
accredited Clinical Trials Units that can manage them. Translation and commercialization (stage 3) will be assisted by the relevant offices at the two universities. The Univ of Dundee Research and Innovation Services, the University of Edinburgh BioQuarter and Edinburgh University's Edinburgh Research provides help on all aspects of commercialization.