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By Chris Talbott, UW Medicine
There is conflicting research on the strength of relationships between retinal biomarkers and Alzheimer’s disease and related dementias. Limited sample sizes, study designs and protocol differences have led to mixed results in exploring whether features on the back of the eye are associated with development of dementia.
A new paper suggests that by adding a home testing element to their research, Dr. Cecilia Lee and her colleagues from the University of Washington School of Medicine and the Kaiser Permanente Washington Health Research Institute have ironed out a difficult wrinkle.
The group believes their study results will move them closer to a reliable way to detect Alzheimer’s disease early. Their paper, published June 25 in the Journal of Alzheimer’s Disease, details progress on the project.
“We know that just looking at the diagnosis of eye diseases can tell us that somebody's at increased risk of Alzheimer's disease,” said Lee, a professor of ophthalmology. “Now we can do so much better with characterizing the eye, particularly the retina, the neural tissue of the eyeball, because we have all these noninvasive techniques. We can measure visual function and characterize microscopic features of the retina.”
Lee’s Eye ACT study recruited 330 participants from within the ongoing Adult Changes in Thought study whose retinas are imaged every two years. About a third can’t come to the clinic for evaluation and need home testing. Since Alzheimer’s is so difficult and expensive to diagnose, the hope is by tracking retinal changes over time, researchers can use artificial intelligence to correlate those changes with the development of dementia and understand at what point these retinal changes occur before or while cognition becomes impaired.
One hitch, however, has been the lack of testing techniques outside of clinic settings. This has meant that potential research participants who could not get to a clinic were left out of the data. These people are often older and have more complex health conditions. Not including them as participants was a potential flaw in study design.
This research was funded in 2019 with a $17.2 million grant from the National Institute on Aging. The grant came after Lee and colleagues published a 2018 study that found a significant link between dementia and age-related macular degeneration, diabetic retinopathy and glaucoma.
The team also found that cataract surgery was associated with a 30% lower risk of dementia in a subsequent study. She hopes the NIA will extend the grant another five years this year so they better understand these results and discover more in this unique population.
“If you ask me about a result, I promise you that I can find a paper that reports a conflicting outcome,” Lee said. “There are a lot of controversies about, say, what part of the retina is associated with Alzheimer's? Is it really Alzheimer's? Or is it any neurodegenerative conditions like Parkinson’s disease, vascular dementia, frontotemporal dementia, and so on? Is it really age-related? Where do you need to look?”
Dr. George Perry, the editor-in-chief of the Journal of Alzheimer’s Disease, agrees and has identified Lee’s work as of particular interest “as the eye changes have been somewhat controversial and this work clarifies.”
Lee and team have been using data gathered from participants in the Adult Changes in Thought study established in 1994 as a collaboration between Kaiser Permanente Washington Health Research Institute and UW School of Medicine. ACT is a living laboratory of aging and the brain that includes health information about Kaiser Permanente Washington participants 65 and over.
The grants have supported continuous regular collection of extensive data for Alzheimer’s disease research and brain aging among others. The ACT information is especially valuable, Lee said, because it is community based, not just highly selected samples from referral clinics. All patients are likely getting the same kind and level of comprehensive medical care as they age.
The study’s investigative team includes expertise in Alzheimer’s disease and related dementia, neuropsychology, neuroimaging, ophthalmic imaging, big data and artificial intelligence. Lee believes the work they’ve done to date has laid the groundwork for moving past the so-far muddled results in this area of study.
“We are already seeing significant results just from looking at the first 330, and then now those people are coming back to follow up,” Lee said. “We are so grateful to our Eye ACT and ACT participants. The study will continue to generate more results and this is what we need.”
This research was funded by the National Institute on Aging (R01AG060942, U19AG066567, U01AG006781). Additional funding included NIH grant OT2OD032644, the Latham Vision Research Innovation Award, the Klorfine Family Endowed Chair, the Karalis Johnson Retina Center and an unrestricted grant from Research to Prevent Blindness. Lee is the Klorfine professor of ophthalmology.
