On the Horizon #139 of 172

Quick retinal scan may spot Alzheimer's years before usual diagnosis

John Murphy, MDLinx

An eye scan of the retina may indicate early signs of Alzheimer’s disease years before clinical symptoms arise, according to research presented May 5, 2016 at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), in Seattle, WA.

Eye scan for Alzheimer's disease found by Brown University researchers

Amyloid beta inclusion bodies (circled in red) in the retina may indicate early Alzheimer’s disease in subjects who don’t yet show cognitive symptoms. (Images: Peter J. Snyder, PhD)

Because the retina is an extension of the central nervous system, recent research has focused on identifying neurological diseases, like Alzheimer’s, in the eye. In this small proof-of-concept study, researchers correlated amyloid beta plaques in the neocortex of the brain with amyloid beta “inclusion bodies” in the retinas of subjects with pre-clinical Alzheimer’s.

“By the time someone is symptomatic and clinically diagnosed with Alzheimer’s disease, the damage has already been done—and it may be too late to intervene,” said lead investigator and neurologist Peter J. Snyder, PhD, Senior Vice President and Chief Research Officer at Lifespan Hospital System in Providence, RI.

“We need cost-effective clinical tools to identify pre-clinical disease on a wide scale. Then we can intervene with new therapeutics as early as possible,” added Dr. Snyder, who is also Professor of Neurology at the Alpert Medical School of Brown University, in Providence.

Previous studies have found amyloid beta plaques in the retinas of clinically diagnosed Alzheimer’s patients, but this investigation took a new approach by studying Alzheimer’s suspects long before they show any signs of the disease.

For this study, Dr. Snyder, co-investigator Len Johnson, MD, Chief of Neuro-Ophthalmology at Rhode Island Hospital, research assistant and PhD student Claudia Santos, and colleagues enrolled 63 adults of retirement age (55 to 75, mean age 61) with no neurological symptoms. Although these subjects showed negative results on cognitive tests of Alzheimer’s, they all had at least two risk factors for the disease—each was a caretaker for a close family member with Alzheimer’s, and each had subjective complaints of memory loss.

“We’re beginning to see that people really are very good barometers of subtle change in their own cognition that we may not be able to recognize clinically for some time,” Dr. Snyder said.

First, these subjects underwent PET imaging of the neocortex to quantify their amount of amyloid beta in the brain. Next, they were given a noninvasive retinal scan using spectral-domain optical coherence tomography (OCT) with blue laser autofluorescence. This identified plaque inclusion bodies, which appeared as tiny, dense, non-reflective spots in the retina. The OCT scan also measured the thickness of the layers of the retina.

“We found fairly good correlation [r = 0.46] between the amount of these inclusion bodies in the retina and the amount of amyloid burden in the brain shown by PET imaging,” Dr. Snyder said. “Now that doesn’t prove causation, but it’s pretty suggestive.”

He also noted that PET scanners are relatively few and far between, while OCT instruments can be found in nearly all ophthalmologists’ and optometrists’ practices. OCT instruments are also less expensive and easier to use in parts of the country, and the world, where no PET scanners are available.

OCT imaging identified another surprising finding in these subjects—the inner plexiform layer of the retina was thickened by inflammation, which may be related to concurrent inflammation in the brain.

“There’s good animal research showing that in the very earliest stage of Alzheimer’s disease, a neuroinflammatory process occurs which involves some edema and some increase in the volume of tissue in the cortex in the brain. And we think that’s happening in the retina,” Dr. Snyder said.

“That region of the retina is rich in the neurotransmitter acetylcholine, which is downregulated very early in the disease process in the brain,” he added. “We don’t think that’s a coincidence.”

If these results can be validated with further studies, the researchers hope that it will eventually result in a screening test for Alzheimer’s disease, which would lead to earlier diagnosis and even preventive treatment.

“This is an exciting result, but we need to replicate this. We need to verify it,” Dr. Snyder said.