• Alzheimer’s disease (AD), the most common form of dementia, accounts for 60-70% of dementia cases.
  • Diagnosis currently involves many lengthy tests, meaning that treatment may be delayed.
  • A new post-mortem study has found significant changes in the retinas of people who had mild cognitive impairment or AD before death.
  • These findings may lead to a non-invasive diagnosis of AD by retinal screening.

According to the World Health Organization, more than 55 million people worldwide have dementia, and some 10 million people are diagnosed with the disorder each year. In the United States alone, about 5.8 million people are living with dementia, and the Centers for Disease Control and Prevention (CDC) predicts that the number will rise to 14 million by 2060.

If a person starts to show signs of cognitive impairment, it is important to seek an early diagnosis. Prompt diagnosis of dementia will allow the individual and their carers time to plan for the future, and to access treatments that, although they cannot cure the disease, can slow or delay symptoms, and that can help manage symptoms.

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Alzheimer’s disease may have many effects on the retina, which could aid in diagnosis. Alice Eremina/EyeEm/Getty Images

Currently, dementia diagnosis relies on a number of evaluations, including cognitive tests, brain scans, cerebrospinal fluid (CSF) tests, blood tests, psychiatric evaluations, and genetic tests. These can take a long time and be costly, so much recent research has focused on finding faster, less-invasive methods of diagnosing dementia.

Biomarkers are showing promise as a diagnostic tool. Although these are minimally invasive, most involve taking blood or CSF. Newer research has shown that retinal screening may detect signs of AD, making this a potential method for diagnosis.

Now, a post-mortem study has found that people with cognitive impairment or AD have many retinal changes that are not seen in the retinas of cognitively healthy people.

The study, led by researchers from Cedars-Sinai Medical Center, is published in Acta Neuropathologica.

“For several years, scientists have been exploring how to use the imaging technology used in ophthalmology to measure levels of Alzheimer’s biomarkers in our eyes. The ability to easily detect the biological hallmarks of Alzheimer’s in the eye is intriguing in that it may provide the ability to detect the disease in a noninvasive manner, in earlier stages before symptoms appear.”

Dr. Percy Griffin, Alzheimer’s Association director of scientific engagement.

The researchers examined retinal and brain tissue samples collected over 14 years from 86 human deceased donors with AD or mild cognitive impairment (MCI). These samples were compared with those from cognitively healthy donors.

They found molecular, cellular, and structural changes in the retinas of those with AD and MCI. These changes were not seen in cognitively healthy retinas.

Beta-amyloid plaques (Aβ) are common in the brains of people with AD, and this study found high concentrations of Aβ in the retinas of those with AD and MCI. Research has shown that Aβ42, a longer molecule form of Aβ is particularly important in AD pathology.

“This study confirms that the same cellular, chemical and molecular changes which are in evidence in the Alzheimer’s brain are evident in the retina.”

Dr. Howard R. Krauss, surgical neuro-ophthalmologist and director of Pacific Neuroscience Institute’s Eye, Ear & Skull Base Center at Providence Saint John’s Health Center in Santa Monica, California, speaking to Medical News Today.

This study found a high correlation between the presence of Aβ42 in the retina and cognitive impairment.

The retinal biomarkers were not uniformly distributed throughout the retina. There was a much greater density of Aβ42 in the inner and peripheral than in the central retina.

The researchers also looked at inflammatory markers in the retinas. Microglia are immune cells, the action of which is changed in people with AD and other forms of dementia. Research has found that overactivated microglia increase Aβ and Tau, and promote neuroinflammation.

In this study, the researchers found that retinal Aβ42 and microgliosis were strongly correlated with cognitive status in both men and women. Women, however, showed higher levels of retinal IBA1+ microgliosis than men.

Dr. Griffin commented on this finding:

“Interestingly, the researchers found higher levels of inflammation in the eyes of women compared to men. Given that more women over the age of 65 are living with Alzheimer’s dementia than men, we need to understand these sex differences and how they contribute to risk.”

Examination of the retina and optic nerve can now diagnose many health conditions that are seemingly unconnected to the eye. These include hypertension, diabetes, thyroid disorders, and neurodegenerative diseases such as multiple sclerosis (MS).

This study adds to evidence that retinal examination might also be used to diagnose AD.

However, Dr. Krauss cautioned that the technology is still in its early stages.

“Although there have been technologic advances to date which allow finer and finer anatomic retinal evaluation, and correlations with the degenerative changes of Alzheimer’s disease have been described, there is not yet a technology which allows a retinal scan to diagnose Alzheimer’s disease; the hope, however, is that the technology is ‘around the corner’, but much more investment of research time and money is needed.”
— Dr. Howard R. Krauss

“In that this study has been dependent on a direct sampling of retina to allow direct histopathologic, chemical, and molecular analyses, the results are not directly applicable without surgically obtaining retinal tissue, which would be an impractical suggestion in pursuit of a diagnosis, but the study does encourage us to develop non-invasive tests to analyze the retina in vivo,” he said.

Dr. Griffin also stressed the need for more research:

“Research in this space is still in the early stages, and this tool must be studied in larger, more diverse populations to understand how or if retinal imaging may be a useful Alzheimer’s screening tool in all populations.”

“The Alzheimer’s Association believes in the importance of identifying easy-to-use, non-invasive, relatively inexpensive methods for early detection and diagnosis of Alzheimer’s disease, and has supported a considerable amount of research in this area,” he added.

The findings of this study suggest that retinal examination could one day be a simple, non-invasive test for early AD. But it is unlikely to be soon.

In the meantime, Dr. Krauss advised:

“Consider that the most effective tools today in slowing the progress of Alzheimer’s disease are the same key factors in achieving and maintaining wellness, in general: lifestyle; in other words, don’t wait until you are ill to become well; stop smoking now; stop alcohol and ‘drugs’ now; eat prudently, exercise, sleep well, reduce stress and have regular checkups, vaccinations, and health screenings while you are ‘healthy’.”