Cecilia Lee, MD, MS, Assistant Professor at the University of Washington School of Medicine and Lead Researcher, talks about a study that connect certain eye diseases to increased risk of Alzheimer’s.
Interview conducted by Ivanhoe Broadcast News in July 2018.
Tell me a little bit about the study.
Dr. Lee: We found that people with glaucoma, diabetic retinopathy and age-related macular degeneration are at about forty to fifty percent increased risk of developing Alzheimer’s disease compared to people who do not have those eye conditions.
Why?
Dr. Lee: A lot of people often refer to the eye as their window to the body and what it really is, is that the eye is the window to the brain. The reason is because when the human body develops, the eye actually comes from the same tissue as the brain. So when we look into the eye, hopefully it’s giving us a glimpse of what’s happening in the brain. Our team of researchers was interested in finding this potential connection between the aging eye and the aging brain. So, we thought by looking at the conditions that happen in the aging eye we might be able to learn what else is happening in the aging brain, specifically in Alzheimer’s disease. We used a very large database of almost four thousand study participants from a study called, Adult Changes in Thought, or ACT study. They were followed across almost a quarter of a century and we found that people with those three eye conditions, glaucoma, diabetic retinopathy and age-related macular degeneration, are at higher risk of developing Alzheimer’s disease compared to other people who do not have those eye conditions.
Do you know what the actual connection is?
Dr. Lee: We do not know how these eye conditions are related to Alzheimer’s mechanistically yet. All three conditions do affect the retina, which is connected to the brain and evaluating the retina in more details might give us better idea of this connection.
Eye conditions might reflect that neurodegenerative process has already occurred in the brain. Or some people who develop these eye conditions may be prone to developing Alzheimer’s since neurodegenerative insults have already occurred. Another possibility is that all three eye conditions have multiple mechanisms by which they develop, some of the mechanisms may be similar to Alzheimer’s disease or even be connected. More studies are needed to tease these hypotheses and we are planning on a subsequent study.
Does it mean that you’re going to get Alzheimer’s if you have one of these three eye conditions?
Dr. Lee: Our study results do not mean that anybody who has those eye conditions will develop Alzheimer’s disease. One can think there are a lot of mechanisms related to somebody developing Alzheimer’s disease. That’s probably why all these three conditions can be associated with the disease, yet be very different diseases among themselves. Our study is really the first step in uncovering this important association between the aging eye and aging brain. The next step is really to dig down further in to understanding what types of or what characteristics of those eye conditions are really associated with Alzheimer’s disease.
Was the study completed recently?
Dr. Lee: The ACT study, from which we received our eye study data, is currently ongoing. The ACT study has been recruiting study participants since 1994 from Kaiser Permanente Washington. The participants were dementia-free when they were enrolled and followed until they developed Alzheimer’s disease or any type of dementia. Some patients have been followed for almost thirty years and we are learning a lot about what is going on with cognitive decline and then also at the same time, we’re able to learn what kind of eye conditions they’ve had or have developed before they were diagnosed with Alzheimer’s disease. The study that we recently published, in terms of the association between the eye and the brain, is by far the largest and the first comprehensive study that includes all these eye conditions in association with Alzheimer’s disease.
How difficult has it been to predict Alzheimer’s until now? Is it even possible?
Dr. Lee: It’s not impossible, but it’s very hard to know who will develop and who will not develop. Nowadays, we’re using different machinery such as MRI’s or PET scans or even lumbar puncture to study the biomarkers. But these different machinery and biomarkers are far from perfect. Right now, the best way to predict Alzheimer’s is probably to follow people carefully over time which is what the ACT study does.
That’s why what we found is so important that it’s going to potentially lead us to great screening tools in terms of identifying people at risk of developing Alzheimer’s disease. Or, even we may be able to diagnose Alzheimer’s disease at an earlier stage than what we are able to right now. The goal is that we may be able to use eyes as the window to the brain or as a screening tool. By noticing what’s happening in the eye, we may be able to predict who will develop Alzheimer’s disease and potentially develop treatments that can target those patients. The ultimate goal is to really provide treatment for the patients even before they develop symptoms of dementia.
So, what is the next step?
Dr. Lee: Our studies have shown that the diagnoses of glaucoma, diabetic retinopathy, and age-related macular degeneration are associated with higher risks of developing Alzheimer’s disease. So, now we want to go beyond these findings. We want to learn what exactly or what characteristics of the eye conditions are really associated and are predictive of Alzheimer’s disease. So we are planning a large study with the ACT study participants in terms of following them. First finding out what type of eye conditions or what type of severity they’ve had, and also following them prospectively with beautiful imaging to really understand the link between the eye and the brain.
Are you using all new patients or existing patients?
Dr. Lee: Existing. However, when people are deceased or develop dementia they are terminated from the study. So, we’re always collecting more patients to replace those patients.
When do you anticipate that study will start?
Dr. Lee: We have proposed our next subsequent study and are hoping to receive funding to proceed with it. So, hopefully in a few months.
Do you think this is information doctors could be using now?
Dr. Lee: Yes. I mentioned that our study results should not be alarming to the patients who have these eye conditions. But, the study results should really increase the awareness, especially of ophthalmologists and perhaps primary care physicians, who should really know that there is an important link between these eye conditions and Alzheimer’s disease. So, whenever they see patients that they know have those three eye conditions, maybe they will benefit from further evaluation, especially if the doctors are suspicious of cognitive decline with dementia.
Is there anything else you would like to add?
Dr. Lee: Because the risks were very high, we wanted to make sure that we weren’t just detecting simply risk related to age. So, we tested whether cataract was also a risk factor for Alzheimer’s disease. The reason why we chose cataract is because when people get older, everybody gets a cataract. You could say that cataract is the most age associated condition, but when we tested whether a cataract was a risk factor for Alzheimer’s disease, it was not. That really gave us more reassurance and confidence that these three eye conditions, although they’re more common in the elderly, they are actually very predictive of who is at risk of developing Alzheimer’s disease. The results are very exciting.
We are really living in a very exciting time of clinical research. We are living in an era of Big Data now. Before, a patient might have been seen by an ophthalmologist, the ophthalmologist would scribble down the note on their piece of paper and store it in the file cabinet somewhere. If that patient developed Alzheimer’s disease, he or she may be seen by a neurologist who will also scribble down the note and just file it in the store cabinet. So, we really did not have good way of integrating that important data to be able to do research like ours. Nowadays, all the data is stored electronically and is giving us opportunities to really run powerful epidemiological studies that allow us to uncover these important associations of a devastating disease. We are looking forward to really examining the results of our study and then moving forward with them.
Lastly, this study would not have happened without our collaborators or our team of researchers at Kaiser Permanente Washington and University of Washington. I do want to thank and acknowledge all our study participants. As a researcher myself, I’m constantly humbled by their generosity and commitment to advancing the science and research. A significant portion of the patients have actually agreed to donate their brain when they die to continue this research and I cannot be thankful enough.
Since there’s not a cure for Alzheimer’s, what could be done or what would be the exercise to be done if you saw someone at risk?
Dr. Lee:
Currently, we know that the biggest risk factor for Alzheimer’s is age. For people who are likely to live to 85 and older, which is almost everyone, should do things like regular exercise, stay socially engaged, and reduce cardiovascular risk factors.
In terms of advancing our understanding of Alzheimer’s, the first step is really finding out who’s at risk so we can develop treatments or therapies that can target those patients. By identifying who’s at risk for developing Alzheimer’s even before they develop symptoms of Alzheimer’s, it can help us to really understand the disease so we can develop treatments or therapies that can cure it. The logic of our study would be to find biomarkers that can predict who is at risk of Alzheimer’s disease, or biomarkers in the eye that can teach us about their brain or what’s happening in the brain. This way, we can learn about their disease process and develop treatments that are specific to those patients.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Cecilia S. Lee, MD, MS
University of Washington
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