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Retinal neurodegeneration a red flag for dementia

Jairia Dela Cruz
14 Aug 2018

A thinner retinal nerve fibre layer (RNFL) signals a heightened risk of developing dementia, as shown in two recent studies.

These data have important clinical implications for treatment and prevention of dementia, as well as for future research, according to the investigators. They also point to the potential of optical coherence tomography (OCT) measurement of the RNFL as a noninvasive, relatively inexpensive and rapid screening test for early cognitive changes.

In the first study, a total of 32,038 individuals (mean age 56.0 years; 53.6 percent female) from the UK Biobank underwent baseline retinal OCT imaging and four basic cognitive tests. Results revealed an association between a thinner RNFL and poor cognitive performance. Patients in the thinnest quintile of RNFL were 11 percent more likely than those in the highest quintile to fail at least one cognitive test (≤45.9 vs ≥60.2 μm: odds ratio [OR], 1.11; 95 percent CI, 2.0–2.1; p=0.01). [JAMA Neurol 2018;doi:10.1001/jamaneurol.2018.1578]

Three-year follow-up data in a subset of 1,251 participants (3.9 percent) showed similar results. Those in the two lowest RNFL quintiles had up to a twofold likelihood of having at least one worse test score at follow-up cognitive testing compared with those in the highest quintile (≤45.9 μm: OR, 1.92; 1.29-2.85; p<0.001; 45.9–50.4 μm: OR, 2.08; 1.40–3.08; p<0.001).

“There is strong evidence that a thinner RNFL is associated with adverse cognitive function. Our data also suggest that RNFL thinning precedes cognitive decline in many people and predicts cognitive deterioration,” said lead study investigator Dr Paul Foster from the University College London Institute of Ophthalmology in UK.

The findings presented by Foster and colleagues parallel those of the second study involving 3,289 individuals (mean age 68.9 years; 57 percent female) from the Rotterdam Study, among whom 41 (1.2 percent) already had dementia.

During a mean follow-up of 4.5 years, 86 (2.6 percent) developed dementia, including Alzheimer’s disease (n=68). Thinner RNFL at baseline significantly increased the risk of developing dementia (hazard ratio [HR], 1.44; 1.19–1.75) or Alzheimer’s disease (HR, 1.43; 1.15–1.78). [JAMA Neurol 2018;doi:10.1001/jamaneurol.2018.1563]

Prevalent dementia was associated with thinner ganglion cell-inner plexiform layer (GC-IPL; OR, 1.37; 0.99-1.90) but not RNFL. There was no association found between incident dementia and GC-IPL thickness (HR, 1.13; 0.90–1.43).

“In patients with dementia, damage to brain regions covering the visual tract may cause retrograde degeneration of the optic nerve by affecting the neuronal connections of the visual tract. Subsequently, this neurodegenerative process may manifest itself in the retina initially as thinner RNFL, after which thinning of the GC-IPL follows,” explained principal investigator Dr Kamran Ikram from the Erasmus Medical Center in Rotterdam, the Netherlands.

“Hence, given our findings, it is possible that thinner GC-IPL is reflecting more advanced stages of Alzheimer’s disease pathology. However, an important question remains why thinner RNFL was not associated with prevalent dementia with a similar effect magnitude as the GC-IPL,” he added.

Taken together, the two studies show that RNFL thinning, as assessed by OCT, may be a marker for dementia.

“[T]here is an opportunity to use OCT in clinical or research settings as an accessible and noninvasive tool to help clinicians or researchers in eligibility determination for clinical trials, in monitoring disease progression or in evaluating treatment response,” said Ikram.

“The wide availability of OCT technology in ophthalmic and optometric practices may accelerate the general uptake of this potential screening test,” Foster added.

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