Retinal Changes May Signal Pre-Clinical Alzheimer's Disease Neuropathology

In cognitively normal older people, retinal biomarkers may reflect Alzheimer's disease-related brain abnormalities, according to a small study from South Korea.

Postmortem studies have linked retinal changes to Alzheimer's disease (AD) pathology, Dr. Dong Young Lee and colleagues at Seoul National University College of Medicine note in JAMA Ophthalmology.

But optical coherence tomography (OCT) studies have yielded inconsistent findings, and "whether retinal function, as measured by electroretinography, is changed in preclinical AD has not been investigated," according to the researchers.

To investigate, the researchers did a complete ophthalmic examination, including swept-source OCT and multifocal electroretinography (ERG), in 49 cognitively normal participants (mean age, 71 years). They also underwent amyloid-beta positron emission tomography (PET) and magnetic resonance imaging (MRI).

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Sixteen participants were amyloid-beta positive. Compared with the others, they had significantly reduced inner nasal macular thickness and retinal nerve fiber layer thickness.

Examination of retinal electrophysiologic parameters showed the amplitude of rings 1 to 6 to be similar between the two groups, but the amyloid-beta positive participants had higher implicit time in rings 2 to 6, and particularly so in ring 5.

Swept-source OCT showed that AD-related neurodegeneration correlated with the thickness of the ganglion cell-inner plexiform layer only.

Based on these results, the team developed a model to differentiate between the amyloid-beta-positive and -negative groups and found it to have 90% accuracy.

"Our findings," they conclude, "suggest that retinal biomarkers may be used as a screening tool for early detection of AD, although further evidence to validate the findings (is) needed."

Dr. Dilraj Grewal, co-author of an accompanying editorial, told Reuters Health by email, "A noninvasive retinal biomarker to detect not only those with symptomatic AD, but also those with preclinical AD where lifestyle modifications such as diet, exercise, and cognitive engagement may delay onset, has the potential to have a huge impact in delivering care to our aging population."

"This is an important study towards development of these biomarkers which shows changes in retinal function with delay in implicit time on multifocal ERG and retinal thinning on OCT in eyes of cognitively normal individuals with AD neuroimaging biomarkers (on PET and MRI)," said Dr. Grewal of Duke University School of Medicine, in Durham, North Carolina.

"The study also highlights some of the key challenges in the path to development of retinal imaging biomarkers such as the impact of other neurodegenerations such as diabetes, hypertension or glaucoma and standardization of these measurements across devices and across studies," he added.

Dr. Richard S. Isaacson, director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian, in New York City, told Reuters Health by email, "There is a pressing need to have cost-effective and minimally invasive tests to help diagnose the earliest stages of Alzheimer's. This is an early but important study that found an easy-to-administer test in the ophthalmology clinic can predict the presence of amyloid in the brain, which is the 'bad' protein that builds up in early Alzheimer's."

"Most people," said Dr. Isaacson, who was not involved in the research, "are unaware that Alzheimer's begins silently in the brain decades before the first symptom of memory loss begins, leaving a critical window of opportunity for intervention. In the future, effective treatments will be most likely to have a beneficial effect if begun in this early pre-symptomatic stage."

In an email to Reuters Health, neuro-ophthalmologist Dr. Christine Greer of Weill Cornell Medicine, who also was not part of the research, said, "This study shows promise in utilizing OCT, a non-invasive, fast, cost-effective clinical tool in helping to risk-stratify patients with pre-clinical Alzheimer's disease. Considering there are about 46 million Americans currently affected by preclinical Alzheimer's, an eye test like this may one day be an important tool for early detection, yet further studies in larger more diverse groups are warranted."

Dr. Lee did not respond to requests for comments.

—David Douglas

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