Pauline Anderson

July 27, 2016

TORONTO — Thinning of the retinal nerve fiber layer (RNFL) is associated with poor cognitive function and may be a clinical marker for cognitive decline, a large study shows.

The results indicate that RNFL thinning is likely a marker for cognitive decline that could be used in clinical practice, according to lead author Fang Sarah Ko, MD, an ophthalmologist at the Eye Associates of Tallahassee, Florida.

"I suspect that whatever process is affecting cognition would also affect the nerve fiber layer because it is fundamentally neural tissue," she told Medscape Medical News.

Dr Ko presented her findings here at the Alzheimer's Association International Conference (AAIC) 2016.

Largest Study to Date

The study included participants from the UK Biobank. Participants provided demographic information and blood samples and underwent a physical examination as well as optical coherence tomography (OCT) to measure the thickness of the retinal nerve layer.

Of those invited to participate in the study, 67,321 had retinal measurements taken. Researchers excluded people with any optical disorder, including glaucoma, or vision worse than 20/25, as well as those with any neurologic diseases or diabetes, as these are known confounders. The investigators also excluded people with poor image quality.

The imaging data provided other information on the retinal layer, but for this study the researchers focused solely on the nerve fiber.

After exclusions, 33,068 participants had usable OTC data.

Although other studies have looked at the relationship between RNFL and cognitive function, "I think this is the biggest, probably by several orders of magnitude," said Dr Ko.

A total of 32,038 participants had OCT information and completed four cognitive tests:

  • Prospective memory: This test involves remembering something at a future time point. Participants in this study were told that at the end of the computer session they would be shown colors and figures and would need to remember to carry out a certain task.

  • Pairs matching: Participants were shown several pairs of cards that were then turned face down, and they had to pick them out (there were two rounds of this test).

  • Numeric and verbal reasoning: This series of tests measures the ability to reason with information provided to work out a correct answer to a question.

  • Reaction times: Participants were timed on pushing a button when recognizing objects.

Statistically Significant

Researchers divided participants into categories of RNFL thickness: from under 45 μm to 65 μm and over.

At baseline, the thinner the nerve fiber layer the worse participants did for all four separate tests. This was statistically significant for all tests, and still significant (P < .001) after adjustment for age.

The study also looked at the association of RNFL thickness and the number of "failures" on the cognitive tests. The results here showed that individuals with the thinnest RNFL on average failed the greatest number of tests compared with people with the thickest RNFL. Again, this was statistically significant (P < .001).

The investigators used regression analysis that controlled for several factors that could potentially affect the nerve fiber layer and cognitive function, including age, sex, race, and "deprivation" (using an index that considered home ownership, an overcrowded household, and other factors).

"The things that remained significant were the two rounds of pair matching, verbal and numeric reasoning, and reaction time; prospective memory dropped out," said Dr Ko.

From these analyses, she and her colleagues concluded that people with thinner RNFL at baseline have worse cognitive function.

About 2500 participants repeated the cognitive function testing after 3 years.

Researchers compared this with baseline scores to see whether future cognitive decline can be predicted.

The analysis showed that those with the thinnest RNFL declined more on pairs matching and reaction time.

"You have to remember that this is a much, much smaller group and these are healthy, well-off people," said Dr Ko. "The fact that we found anything was actually pretty surprising."

She added that "this is only 3 years; you don't expect a healthy person to decline very much in 3 years."

She noted that if some participants who were initially excluded were "added back in" (eg, those with worse vision), "we might even see a stronger effect because we were very stringent in our criteria," said Dr Ko.

Readily Available Test

The study also showed that individuals with the thinnest RNFL declined on a statistically significantly greater number of cognitive tests compared with people with a thicker layer.

"I could not find another factor that could account for the change" aside from RNFL thickness," said Dr Ko. However, she noted, Asian people did seem to be "slightly protected" against cognitive decline within those 3 years.

OCT is readily available and used regularly in ophthalmology offices. "I use it every day to take care of patients with glaucoma," said Dr Ko.

It wouldn't be that difficult to put a different algorithm onto the machine to use it for this type of neurologic application, she said.

In addition to conditions such as dementia, Dr Ko sees this tool possibly being used in traumatic brain injury.

A "caveat" of the research is that because this is an older, healthy population, it may not be representative of the United Kingdom.

According to information provided by Dr Ko, an estimated 46 million people are living with dementia. This figure is projected to rise to 131 million by 2050, but if onset can be delayed by 1 year, the global projected number would decrease by 9 million.

Strong, Impressive Research

Suanne Craft, PhD, Alzheimer's Association Medical & Scientific Advisory Council, who chaired a press briefing that included Dr Ko's research, thought the study was "very strong" and the findings "very impressive."

"The number of participants was large, the results were very clear, and the authors were very careful in excluding a lot of other potential complicating factors, so I think it's a very promising finding."

A strength of this research, said Dr Craft, is that the technology is readily available, making it all that much more feasible to implement this imaging "in the near term."

She sees this research as a "very critical first step." The next step, she said, "would be to look at whether it's predictive of Alzheimer's disease."

Alzheimer's Association International Conference (AAIC) 2016. Abstract O3-12-03. Presented July 26, 2016.

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