According to researchers, a future possibility exists where doctors will be able to use eye examinations to identify early indicators of cognitive impairment, even in individuals who do not exhibit any symptoms yet. These findings have the potential to facilitate earlier diagnosis, prior to the onset of symptoms, and could open avenues for new treatments.
Currently, a definitive diagnosis of Alzheimer’s disease (AD) can only be made postmortem. However, recent studies propose the potential for much earlier detection using a simpler and less invasive approach: eye exams. A comprehensive analysis, published in the journal Acta Neuropathologica, outlines how changes in the retina correspond to brain and cognitive changes in patients with Alzheimer’s disease.
“These findings may lead to the development of imaging techniques that would be able to diagnose Alzheimer’s disease earlier and more accurately,” said senior author Maya Koronyo-Hamaoui, PhD. She is a professor of neurosurgery, neurology, and biomedical sciences at Cedars-Sinai in Los Angeles.
Providing a Glimpse of What’s Inside the Brain
Researchers are well aware of the established link between the retina and the brain. The retina, which forms part of the central nervous system, consists of layers of nerve tissue that detect light and connect the eye to the brain. Remarkably, unlike the brain or spinal cord, the retina can be directly imaged, making it an ideal subject for scientific investigation. In fact, a significant amount of knowledge about the brain has been derived from studying this particular eye component, as highlighted by the National Eye Institute.
For several years, scientists have been exploring the utilization of ophthalmology’s imaging technology to measure levels of Alzheimer’s biomarkers in our eyes, as noted by Percy Griffin, PhD, the Director of Scientific Engagement at the Alzheimer’s Association.
“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,” said Dr. Griffin. He was not part of the study.
According to the BrightFocus Foundation, a nonprofit organization focused on brain and eye research, approximately 500,000 individuals in the United States receive an Alzheimer’s diagnosis annually. A study published in January 2022 in The Lancet predicts that within three decades, the number of American adults aged 40 and above living with dementia will increase from 5.2 million to 10.5 million.
Researchers Tested Eye and Brain Tissues From Those Suffering from Dementia
Researchers conducted a comparative analysis using human eye and brain tissues obtained from deceased donors. They examined samples from donors who had normal cognitive function, mild cognitive impairment (MCI) at the early stages of Alzheimer’s disease, and later-stage Alzheimer’s disease dementia.
The researchers focused on the retinas and studied markers of inflammation, functional cell loss, and various proteins associated with Alzheimer’s disease (AD) present in both retinal and brain tissues.
The results revealed an excess of a protein called beta-amyloid 42 in the retinas of individuals with MCI and AD. The accumulation of this protein was particularly pronounced in the inner layers and peripheral regions of the retina. In individuals with AD, this protein forms plaques that disrupt normal cell function and collect between neurons, as explained by the National Institute on Aging.
Furthermore, there was a buildup of beta-amyloid protein in the ganglion cells of the retinas of individuals with MCI and AD. Ganglion cells serve as a “bridge” that connects retinal input to the visual processing center in the central nervous system.
Individuals with MCI and AD also exhibited a higher number of microglial cells, which are immune cells in the brain that target harmful proteins and infections. However, these cells demonstrated defects and did not function in the same way as those in individuals with normal cognitive function, according to Dr. Koronyo. “In people with mild cognitive impairment and Alzheimer’s disease, only about 20 percent of the microglia are engaging and doing their role of removing the toxic abnormal proteins,” she says.
Retinal Changes ‘Mimicked’ Changes in Brain Connected to MCI and AD
The authors of the study discovered that certain molecules and biological pathways are accountable for inflammation, as well as cell and tissue death, in the retinas of individuals with Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD).
Furthermore, the observed alterations in the retina exhibited a correlation with changes occurring in the brain regions associated with memory, navigation, and the perception of time.
“Changes that were in the brains of people with MCI or AD were mimicked or predicted by changes seen in the retina,” said Koronyo. According to her, even individuals who seemed to be cognitively normal or had very mild mild cognitive impairment (MCI) exhibited retinal changes, suggesting that these changes could potentially serve as an early indicator of future cognitive problems.
Next Step: Monitor the Cognitive Changes in Actual Patients
These findings are very exciting because this would mean that the succeeding step would be to image patients who are still living, as per the authors.
“Because these changes correspond with changes in the brain and can be detected in the earliest stages of impairment, they may lead us to new diagnostics for Alzheimer’s disease and a means to evaluate new forms of treatment,” said coauthor Keith L. Black, MD. He is the chair of the department of neurosurgery at Cedars-Sinai. He made this statement in a press release.
Technology Needs to be Studied in Larger, More Diverse Populations
Dr. Griffin stressed the fact that this latest research saw higher levels of inflammation found in the eyes of women when 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,” he says.
“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,” Dr. Griffin also said.
Blood Tests, Instead of Retinal, May Be the Future of Diagnosing and Monitoring AD
“The idea that there’s a link between the eye and Alzheimer’s disease has been around for a while,” said Constantine Lyketsos, MD. He is a professor of psychiatry who specializes in dementia at Johns Hopkins Medicine in Baltimore and he also was not part of the study.
Dr. Lyketsos remains skeptical about the potential impact of the correlation discovered in this study, which suggests a link between the progression of Alzheimer’s disease in the brain and biomarkers present in the retinas. Although intriguing, he doubts that this finding will significantly alter the current methods of diagnosing Alzheimer’s disease.
“The potential for this to eventually be used to study the eye in a living person is intriguing, but this technology would also be competing with a variety of other methods that we know are pretty accurate in telling us how much pathology is in the brain of someone. I’m not sure that this is really going to change the field that much,” he explained.
The gold standard for detecting AD is still in autopsy. However, there also other effective ways to measure probable Alzheimer’s disease progression in those who are still alive. These are brain imaging studies, PET scans, and MRIs, alaborated Lyketsos.
“We are also very close to having blood tests that tell us how much brain AD pathology an individual has,” he said. In a research paper published in December 2022, a test was introduced that can assess the levels of a hazardous protein closely associated with the onset of Alzheimer’s disease (AD) even before any signs of cognitive decline manifest.
Scientists are optimistic that this straightforward blood test could provide a cost-effective means to gain insights into brain activity. Furthermore, it has the potential to identify individuals who are at risk of developing AD, eliminating the need for invasive procedures like lumbar punctures or costly imaging techniques.
“I think the blood tests are going to be much simpler and easier to use because studying the eye requires specialized equipment,” Lyketsos said.
“The Alzheimer’s Association believes in the importance of identifying easy-to-use, noninvasive, relatively inexpensive methods for early detection and diagnosis of Alzheimer’s disease and has supported a considerable amount of research in this area,” Griffin explained. He states that in order to achieve that goal, the organization has formed the Global Biomarker Standardization Consortium (GBSC) with the aim of standardizing and validating biomarker tests for global use in clinical practices.
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