Eyeworld

EW RETINA 44 by Vanessa Caceres EyeWorld Contributing Writer Because the retina can be im- aged at a particularly high resolu- tion, it is an excellent biomarker for Alzheimer's disease, Dr. Koronyo- Hamaoui said. Dr. Black and the NVI team are currently in the process of getting FDA approval for this, with the use of a high-resolution screen- ing tool that can predict disease pro- gression. "I think it'll accelerate the ability to develop treatments. We'll be able to see responses to therapy noninvasively and do it repeatedly," she said. However, this approach still needs to be validated in hun- dreds of patients, she said. Looking ahead at implications More randomized controlled trials are needed before retinal detection methods for Alzheimer's disease are used regularly, Dr. Hartley said. However, he also thinks it's a matter of when—not if—such retinal exams will reach the clinic. Eye doctors should stay aware of clinical trials in this area that could benefit patients, Dr. Hartley said. The Alzheimer's Association awards research grants and advocates for increased funding from the U.S. government to fund Alzheimer's research, so researchers in this area should apply for available grants, he added. Informally, retinal specialists can be on the lookout for early signs of disease toward the far periphery of the retina, said Dr. Koronyo- Hamaoui, who added that their lab is now working on mapping the geometrical regions that are hot spots affected by Alzheimer's disease. However, the more specific imaging approach developed at her lab is not yet available. "Hopefully in a year or so, we'll have it ready," she said. EW Editors' note: Dr. Koronyo-Hamaoui has financial interests with NVI. Dr. Hartley has no financial interests related to his comments. Contact information Hartley: mcampea@alz.org Koronyo-Hamaoui: Maya.Koronyo@cshs.org he said. Researchers are working to develop drugs that slow down or prevent disease—a major goal as there is otherwise no treatment for Alzheimer's. Closer look at research One researcher who has delved deeply into early signs of Alzhei- mer's disease in the retina is Maya Koronyo-Hamaoui, PhD, assistant professor of neurosurgery and bio- medical sciences, and research sci- entist, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai, Los Angeles. In 2010, her team, in collaboration with Keith Black, PhD, profes- sor and chair of the Neurosurgery Department, and Yosef Koronyo, published the first discovery of am- yloid beta in the postmortem retina of Alzheimer's patients. Since then, they have developed a method of imaging the retina with the use of a contrast agent to assess for amy- loid beta deposits. The researchers, with a team at NeuroVision Imaging (NVI, Sacramento, California), have further used a proprietary formula- tion of curcumin—an ingredient in the spice turmeric—as a fluorescent contrast agent in humans. In animal models, they have used a pure cur- cumin injection. "When we shine a light on the retina, it is absorbed by curcumin bound to amyloid plaques and emits specific wavelengths that allow detection and quantification of these plaques. We can dissect the amount of amyloid beta in the retina and see changes in individual plaques over time," she said. Dr. Koronyo-Hamaoui and col- leagues have done work in animal and cadaver eyes, and they also have a completed proof-of-concept trial. At the most recent Society for Neuroscience meeting in San Diego, they presented findings on degener- ation of specific neuronal cells in the retina associated with inflammation typical of what's found in the brains of Alzheimer's patients. Howev- er, these are new findings for the retina. "We found that the disease in the retina of Alzheimer's patients mirrors what's found in the brain," she said. check for disease signs. This is where researchers have identified how the retina can show early signs of the disease with the buildup of plaque and thinning of the retinal nerve fiber layer. "Some of that [thinning] we see with age, but some of it is more rapid when we see people who develop Alzheimer's," Dr. Hartley said. Although the thinning of the retina may not be the only sign of Alzheimer's disease, it could be used to suggest signs of a cognitive decline problem. Retinal imaging is an easier test than currently used methods for Alzheimer's diagnosis; yet anoth- er advantage is that many elderly patients already visit their eye doctor for annual vision screenings. If research continues to show the value of retina imaging for the early detection of Alzheimer's, it could be something that ophthalmologists will check for, just as they check for signs of glaucoma and vision changes. The eye doctor may not actually diagnose Alzheimer's disease but would use those retinal imaging changes over time to recommend a referral to a dementia specialist if needed, Dr. Hartley said. Those annual exams also give clinicians a baseline image of the retina so they can later examine how the retina has changed over time—and how rapidly those chang- es have taken place. The eye is not the only area where there are promising findings for an Alzheimer's disease diagnosis. There are a number of studies relat- ed to odor identification impairment in Alzheimer's patients. Studies in both areas have been published in journals and presented at the annual Alzheimer's Association Internation- al Conference. Early diagnosis of Alzheimer's disease is crucial because the current crop of drugs approved by the Food and Drug Administration (FDA) is most beneficial in the early stages, Dr. Hartley said. These symptomatic drugs can help improve memory, but they do not prevent disease. "As the disease progresses, it catches up with the brain cells. At some point, the drugs don't benefit the patient," More researchers find retina could provide noninvasive, easy test for cognitive decline A lzheimer's disease affects more than 5 million people in the U.S. and is the sixth leading cause of death, according to the Alzheimer's Association. It often cannot be diagnosed early on, and the currently available drugs do not stop or prevent the disease. However, accumulating research finds that ophthalmologists may have a role in detecting the disease in its earlier stages, so patients can be referred to dementia specialists and obtain symptomatic drugs if needed. "What we've seen over the last 2 or 3 years at our annual meetings is a common theme of looking at the eye and understanding how it relates to Alzheimer's disease," said Dean Hartley, PhD, director of science initiatives, Alzheimer's Association, Chicago. "We need more validation of this information, but there are different independent studies to suggest the validity of using the eye as a useful tool." How it works Amyloid beta plaque is a hallmark of Alzheimer's disease, and it's usually identified in the brain with PET im- aging—an option that can be $3,000 to $7,000 per test, Dr. Hartley said. This test is not always available, nor is it always done because of the high price tag. As a result, dementia specialists and neurologists use other signs and symptoms to make an Alz- heimer's diagnosis. These include a review of family history, blood work, and an MRI to rule out other causes, such as a tumor. Another part of the diagnosis is a neuropsychological exam to help pinpoint memory and planning problems, Dr. Hartley ex- plained. About 70% of people with Alzheimer's disease can be diagnosed with these components. However, clinicians who treat Alzheimer's disease need a noninva- sive and easily repeatable method to Retina may be an early window to Alzheimer's disease January 2017

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