Retinal Nerve Thinning May Predict Cognitive Decline

Individuals with a thinner retinal nerve fiber layer were twice as likely to experience cognitive decline over 3 years, a large study has found. The researchers included more than 30,000 UK adults (aged 40 to 69) and found that people with the thinnest retinas were 11% more likely to fail a series of tests designed to assess memory ability, reaction time and reasoning.

The retina is a layer of light-sensitive tissue lining the back of the eyes. The cells of the retina convert light signals coming into the eye into neural signals the brain can interpret.

Tests to spot early-stage memory decline are in high demand, so these results will spark interest. But they are not proof that an eye test can predict memory decline.

Most people were only tested once. We don’t know if performance on these tests was typical, and whether scores would have declined over time. Despite media reports to the contrary, no participants were reported to have dementia and we don’t know what the test results meant in terms of their daily memory or functioning.

We don’t know the significance of the thinner retinas – it could simply mean these participants had poorer vision. Poorer vision may mean they were less able to complete the test, not necessarily that they had worse memory or thinking skills.

Also, mental decline and a thinning of the retina could be two unrelated consequences of ageing, and may not necessarily be causally linked.

Measuring Retinal Thickness

The study, conducted by researchers from University College London, University of Oxford, University of Edinburgh and Topcon Healthcare Solutions Research and Development, used data from an ongoing cohort study called the UK Biobank, which is looking at 502,656 residents from the same community who are aged 40 to 69 and registered with the NHS.

The study aimed to use data from this healthy cohort to see whether measuring retinal thickness could indicate mental decline. There is some evidence to suggest that such a decline could be linked with a thinner retina.

Prospective cohort studies (which follow people over time) usually set out to examine the effect of one particular thing (in this case, retinal thickness) on a particular outcome (brain test scores). This involves assessing the general health of the people in the study and taking into account (controlling for) any other thing that may potentially influence the outcome.

The researchers in this UK Biobank study only assessed people at a single point in time. So they may not have taken into account every possible thing that could have influenced brain test scores.

The Research Methodology

The UK Biobank collected data between April 2007 and October 2010 at 22 assessment centres in the UK. Although a large range of information is collected for all participants, eye examination results and brain function test results were not added until 2009 to 2010. Eye tests were carried out in 119,573 participants.

In total, 67,321 participants had a specialised imaging test called retinal optical coherence tomography (OCT). This examines the retina in detail and can measure its thickness. A common use for this is in the assessment of glaucoma, where there is increased pressure in the eyeball (associated with a thinner retina).

The researchers excluded participants who had problems with their eyes, such as recent eye surgery, glaucoma or diabetes.

Four basic brain function tests were carried out during 2009 to 2010, they examined:

  • memory, including pair matching testing (spotting and then remembering identical pairs, such as shapes or images)
  • numeric and verbal understanding
  • problem solving
  • ability to think and understand things in a logical way

Results were analysed from 32,038 people of average age 56 (48% of the original cohort). The same brain function test was carried out again a few years later on only a small fraction of these people (1,251 – 4%).

Basic Results

The researchers explored associations between retinal thickness and brain function, taking into account the following potential confounders:

  • age
  • gender
  • race/ethnicity
  • height
  • refraction (the eyes ability to focus)
  • intraocular pressure (the fluid pressure inside the eye)
  • education
  • socioeconomic status

A thinner retina was associated with poorer performance on the brain function tests. Those with the thinnest retinas were 11% more likely to fail at least one mental test (95% confidence interval (CI) 2% to 21%).

To put that into context, 7% of people with the thinnest retinas failed 2 of the 4 tests compared with 4% of those with the thickest retinas.

Of the 4% of participants who had follow-up mental tests, those with the thinnest retinas were almost twice as likely to score worse in at least one of the follow-up tests (odds ratio (OR) 1.92, 95% CI 1.29 to 2.85).

Conclusions

The researchers conclude that:

“a thinner RNFL [retina] is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention and treatment of dementia.”

This study seems to confirm an association between retinal thickness and performance on brain function tests.

However, we shouldn’t interpret this to mean that looking at retinal thickness could detect people in the early stages of dementia.

This study did not examine retinal changes and mental decline over a long period of time. Only 4% of people in this study had follow-up brain tests 2 to 3 years later. We don’t know whether their performance on this test was typical. For example, some of the low scores may have been caused by feeling unwell or tired at the time.

If there is a true link between thinner retinas and poorer brain performance, the interpretation of this is difficult. It could be that thinner retinas and poorer mental ability are just general indicators of ageing, with no direct link between the two.

It’s also possible that people with thinner retinas had poorer vision, so were less able to complete the tests – not that they necessarily had lower mental ability.

And bear in mind that the results are based on only a subsection of the UK population who were mainly white, middle class and educated, meaning the study results are not representative of the whole UK population.

The study is of interest but the value of eye testing as a way of predicting mental decline or dementia is unclear at this stage. A diagnosis of dementia is unlikely to ever be based solely on an eye test.

For anyone who is worried about mental decline, worsening vision or both, routine tests are available and can be carried out by your GP and optician.

The study received combined funding from the International Glaucoma Association, University College London and the National Institute for Health and Research.

Ko F, Muthy ZA, Gallacher J, et al.
Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive DeclineA Study Using Optical Coherence Tomography
JAMA Neurol. Published online June 25, 2018. doi:10.1001/jamaneurol.2018.1578

Image: Cyril Rana/Flickr