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One Day, a Simple Eye Exam Could Detect Alzheimer’s

April 13th, 2018

What if getting a reliable diagnosis for Alzheimer’s was as easy as visiting your doctor for an eye exam? That’s the question Peter J. Snyder, Ph.D., Senior Vice President and Chief Research Officer at Lifespan Hospital System, posed when he started studying retinal imaging, the process of looking deeply into the eye in order to get an idea of what might be happening inside the brain.

Until recently, there was no way to confirm an Alzheimer’s diagnosis until after death during an autopsy. Now, doctors can look at PET scans or order a cerebrospinal fluid tap to measure levels of beta-amyloid protein in the brain, which most scientists believe indicate Alzheimer’s. But both are expensive, invasive and not covered by insurance. A lack of noticeable biomarkers, measurable indications that something is wrong, means that most people don’t know for sure whether they have Alzheimer’s or another type of dementia until an autopsy confirms it after death.

Snyder says that indications of Alzheimer’s are present in our eyes, which he calls “an extension of our central nervous system.” If patients had access to a simple test that could measure the levels of amyloid reflected in the eyes, a swifter diagnosis process could take place, which research shows allows people to be more independent for a longer period of time. And according to Snyder, studies suggest future treatments that might be able to slow or stop Alzheimer’s will hinge on catching the disease in the early stages, rather than waiting  to go to the doctor until the symptoms start interfering with day-to-day life.

We spoke to Snyder about how retinal imaging works, and how soon it will be available for the everyday person.

  • Retinal imaging that measures beta-amyloid, the protein that accumulates and forms into plaques in Alzheimer’s, could help patients get a diagnosis years earlier
  • The retina is considered part of the central nervous system that has evolved to protrude outside of the body
  • Getting an earlier diagnosis could lead to better outcomes for patients, and could help identify people who will develop symptoms of Alzheimer’s in coming years and may be the best candidates for clinical trials aimed at finding a cure

Being Patient: You’ve been working toward diagnosing Alzheimer’s with retinal imaging. Can you tell me about that?

Peter Snyder: Retinal imaging is a new imaging technology in neurology. I am using a technology that is based on infra-red laser scanning of the retina that has been used in opthamology to look at diseases like macular degeneration and glaucoma.

Being Patient: How does that work when looking at the brain?

Peter Snyder: The retina is really an extension of our central nervous system. It is part and parcel of our brain, but it’s actually exposed nervous tissue. It’s often referred to as a protrusion of the brain. The imaging technology that I am relying on allows for light microscopic precision to image the retina in living people without any intervention and really without any pain or risk.

It’s a novel way of looking at changes that we know are happening centrally in the brain related to the disease. There’s cell death, there are changes in specific parts of the brain and there are changes in the pathways that connect different regions. We can see all that in the retina—that’s my belief, anyway.

Being Patient: How do you hope to use it for Alzheimer’s?

Peter Snyder: Alzheimer’s disease has a very, very long prodrome, [the time patients are have no symptoms, but show signs of Alzheimer’s in the brain], that can last decades before there is clinical conversion to disease. Once a patient clinically converts, we are fighting an uphill battle trying to save tissue or reverse the process that has been going awry, potentially for decades. What I hope is to arrive at a way of determining risk and marking change in people who are not yet symptomatic, but are likely to become symptomatic in five or ten years.

Being Patient: How do you plan to measure that? By looking at amyloid, or just changes in the retina in general?

Peter Snyder: There are some groups looking at trying to image amyloid, specifically in the retina, and that is proving to be quite difficult. The most advanced approach at the moment to look at amyloid directly uses a binding agent that you have to administer orally for several days ahead of time. And it’s made from curcumin or turmeric—it’s one of the spices that’s in curry.

We are finding that not all the formulations [of the binding agent] are the same, and we are getting a lot of mixed results.

Even if we can use curcumin to identify amyloid in the retina, having people take it for three or four days ahead of time at high dose doesn’t make it easily applied as a screening tool. I am trying to look at changes in the ultrastructure of the retina that would signal the health of the cells that the amyloid would be attacking. I am looking at cell death and change in myelination of fibers leading into the optic nerve.

The earliest change that I can find is a change in a retinal nerve fiber, which is mostly made up of axons that are myelinated, that branch off of ganglion cells and head towards the optic nerve, and those are the axons we are losing them first.

And that actually goes with a lot of what we know of what’s happening in the brain itself, which is exciting. With that marker, we may be on the path towards developing a retinal imaging biomarker that is really very simple to score and to image. It’s much less expensive than other imaging modalities that we have.

If we were able to have that kind of imaging marker that we compare with lifestyle risk markers and other medical factors, it will aid in screening people.

Being Patient: That reminds me of other less invasive tests for Azheimer’s, like the peanut butter smell test that went viral. But that’s not measurable like a retinal scan.

Peter Snyder: The problem with some of these screening measures is that all of these have false negative and false positive rates. There is some basis for the peanut butter test, though I haven’t seen the video, I have read the literature. The sense of smell is largely under the control of the cholineric system, which is affected very early in the disease. The problem is that there’s so much individual variability in smell in the first place.

That kind of home screening measure just isn’t reliable in predicting a future diagnosis. Maybe in combination with 10 other things, but for people to try it at home and think that it’s actually “predictive” … there is too much error.

Being Patient: Is that kind of variability present in retinal imaging?

Peter Snyder: Obviously, people won’t do retinal imaging in their kitchens. But, any of these screening tests will have false positive and false negative error rates. That’s what I meant before when I said I don’t think it’s going to be the definitive test. What I do see is it fitting into a logical diagnostic process that allows us to more rapidly identify people who are high risk who should be followed and should get additional imaging or be put into a clinical trial.

I don’t expect that, any marker I develop in the retina would be used by itself to make a definitive diagnosis. It’s part of our tool kit—and to be honest with you we don’t have enough tools yet; we need more.

Being Patient: What would you say to people who don’t want to know what their retinal scans show? Like with genetic tests for Alzheimer’s, some people don’t want to know, because right now there’s really nothing they can do about it. How do you convince those people to do a test like this?

Peter Snyder: Yeah, this is a tough ethical problem. But when I’ve provided PET imaging results or genetic results back to people who are in my clinical trials or to my patients, I often find that they are not surprised—that they had some suspicion. I do believe that there is really some truth to the idea that worrying about your own cognitive changes is a risk factor. Because we are all very good at measuring any subtle change in ourselves.

We as individual people are most likely to notice something that is changing before those around us would begin to notice.

Peter Snyder: And even PET imagined results for the amyloid positive are not a guarantee that you are going to get the disease. It just puts you in a different risk category. And we do know that there are some lifestyle changes that people can make that may slow progression of the disease. Exercise, being chief among them, a healthy diet, keeping your weight down, better sleep hygiene—they add up. None of them are magical, but they add up, and what I find is that people who are told that they are in a risk group actually make some of those lifestyle changes.

One of the benefits being in the clinical trials, is that you are followed regularly, and that’s a comfort. I have a lot of patients who are in clinical trials with me, because they just know I am going to be paying attention to subtle changes and they know that I will refer them or intervene when the trial is over, if they need it.

Being Patient: When do you think retinal imaging will start showing up as a diagnostic tool for people outside of clinical trials?

Peter Snyder: I would say that the retinal imaging is still in its early days; it needs to be replicated. We are hoping that in five or six years’ time we may have something that is ready for use. It may be one day the case that you can be followed by an eyecare specialist and if they notice a change, you’d be referred on. That may be a way to screen large populations of people, because everybody over the age of 45 or 50 needs glasses at some point.

This interview has been edited for length and clarity. 

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