August 23, 2018

expert reaction to eye test to detect pre-clinical alzheimer’s disease

Researchers, publishing in JAMA Ophthalmology, reported that changes in the retina were associated with increased likelyhood of preclinical Alzheimer’s disease.

Dr Imre Lengyel, DFP Study Ophthalmology Lead and Senior Lecturer, Queen’s University Belfast, said:

“This study is part of the recent trend in which more and more associations between dementia and morphological changes in the eye are being uncovered in cross-sectional studies. Whilst this study has statistically significant findings the numbers are too small to make conclusions for the population. It is also important to remember that these findings are associations and not proof for causality and the molecular correlations are still in their infancy, often not reproducible.

“Future prospective and, most importantly, longitudinal studies will be needed to uncover causal relationships and prognostic values Studies, like the Deep and Frequent Phenotyping (https://mrc.ukri.org/news/browse/world-s-most-in-depth-study-to-detect-early-signs-of-alzheimer-s-disease/), the World’s most in-depth study to detect early signs of Alzheimer’s disease, will build on the successes of these smaller and more restrictive studies by incorporating useful methodologies into the study design, where possible. With these progresses the eye is becoming a “window to the brain”. Imaging the eye will provide an inexpensive, well tolerated and quick insight into how diseases progress in the brain.”

Dr Doug Brown, Chief Policy and Research Officer, Alzheimer’s Society, said:

“Testing whether changes in the eye, such as those in the retina, might be an early sign of dementia is a fascinating area of research. Yet it is simply too soon to hail this as a new way of diagnosing dementia.

“Research has recently suggested that amyloid, the protein that builds up in a brain with Alzheimer’s, might cause changes to the retina during the course of Alzheimer’s disease. However, although well conducted, this study was very small, including only 30 people who were studied over a very short amount of time. And without confirming that any of the people with preclinical Alzheimer’s actually went on to develop the disease, we would need to see this carried out on a much larger group over a longer period of time to draw any firm conclusions.

“With 1 million people set to develop dementia by 2021, the need has never been greater to diagnose dementia early on. The earlier treatment is started, the more effective it can be – that is why Alzheimer’s Society researchers are working tirelessly to find ways to diagnose dementia as soon as possible.”

Dr Sara Imarisio, Head of Research, Alzheimer’s Research UK, said:

“Alzheimer’s disease can get underway in the brain up to 20 years before symptoms start to show. As future treatments are likely to be most effective when given early, it is critical we find ways to detect the earliest signs of Alzheimer’s disease in the brain.

“While there is currently no single reliable biological test for Alzheimer’s, brain scans and spinal fluid samples taken by lumbar puncture, can reveal some changes linked to the early stages of the disease.

“In this study, researchers linked features of the eye, including the thickness and width of a part of the retina, to biological indications of Alzheimer’s, but did not go on to see if participants actually developed symptoms of the disease.

“While the eye tests used in this research are relatively quick, inexpensive and non-invasive, as only 30 people took part in the study, we still need to see more research before we can tell how useful this method could be for highlighting early signs of Alzheimer’s.

“Alzheimer’s Research UK is currently co-funding a pioneering research study with charity Fight for Sight at Moorfields Eye Hospital that is using a machine learning approach to analyse over 2 million eye scans to look for features that could indicate the presence of diseases like Alzheimer’s.”

Prof Martin Rossor, NIHR National Director for Dementia Research, University College Hospitals and Professor of Clinical Neurology, UCL, said:

“Alzheimer’s disease is difficult to diagnose in its early stages and the tests available are expensive compared with the reported eye examination. However, the variability in the measures used and the very small number of individuals examined means that a lot more work needs to be done before this might be added to the Alzheimer diagnostic battery.”

Prof Nick Fox, Professor of Neurology, UCL and Associate Director of UK Dementia Research institute at UCL, said:

“This is really a very small study – of just 30 people. And although there were interesting and statistically significant optical coherence tomographic (OCT) differences between those who did and those who did not have positive biomarkers for Alzheimer’s disease, there was a lot of overlap between the groups. So from this study we really do not know if this will be useful as a predictive marker – we need follow up of these individuals and replication.”

Prof Masud Husain, Professor of Neurology, University of Oxford, said:

“The findings are intriguing. It is increasingly becoming apparent that the eye provides an important window on what might be going on in the brain.

“Although these results suggest that it might be possible to detect early stages of Alzheimer’s disease using cheap and rapid eye scanning, we have to consider them with caution.

“The numbers of people tested here were extremely small and it would be premature to come to any general conclusions from these findings. Nevertheless, this is a promising avenue of research which needs to be followed up with larger studies.”

Prof Robert Howard, Professor of Old Age Psychiatry, UCL, said:

“As we seek to make the diagnosis of Alzheimer’s disease earlier than when dementia indicates that large numbers of brain cells have been destroyed, we need to find simple, convenient and cheap markers of pathology. At present, only examinations of spinal fluid and expensive PET scans offer reliable detection of these earliest stages.

“In this study, relatively simple measures of the architecture of the retina, which is easy to view, were able to identify people who were at the very earliest stages of Alzheimer’s disease. But the numbers of people involved were small (only 14 with early Alzheimer’s disease) and so the results should be treated as preliminary but potentially exciting.

“A cheap, non-invasive and reliable screening test for the earliest stages of Alzheimer’s disease would speed up the development and testing of treatments that can stop dementia.”

* ‘Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings’ by O’Bryhim et al. was published in JAMA Ophthalmology on Thursday 23^rd August.

Declared interests

Dr Doug Brown: “No interests to declare”

Dr Sara Imarisio: “No conflicts of interest”

Prof Martin Rossor: None received

Prof Nick Fox: “No conflicts to declare that I am aware of”

Prof Masud Husain: “I don’t have any conflicts of interest”

Prof Robert Howard: None received