Retinal neurodegeneration was linked to cognitive decline, adding to a growing literature that suggests retinal structures may be biomarkers for dementia, according to results from two prospective studies.
A thinner retinal nerve fiber layer (RNFL) was tied to worse cognitive function in people without neurodegenerative disease and greater odds of future cognitive decline, reported Paul Foster, PhD, of the University College London, and colleagues, for the U.K. Biobank Eye & Vision Consortium.
And among Rotterdam Study participants in the Netherlands, thinner RNFL was associated with increased risk of dementia, including Alzheimer’s disease, according to M. Kamran Ikram, MD, PhD, of Erasmus MC University Medical Centre.
Both studies, published in JAMA Neurology, used optical coherence tomography (OCT) scanning to assess eyes.
“Our primary motivation was to confirm if the RNFL-cognition association held true in the very early stages of cognitive decline,” Foster told MedPage Today. “Our results suggest it does. This is important because, between 2002 and 2012, 99% of clinical trials into treatments for Alzheimer’s disease failed. A probable reason for the high failure rate is that treatments are being tested on those who already have irreparable damage to the brain.”
The eye is an easily accessible outpouching of the brain and retinal changes can parallel cortical findings, noted Christine Nguyen, PhD, of the University of Melbourne in Australia, who was not involved in either study “These two studies show in large cohorts that the axonal layer of retinal ganglion cells in the eye appears to be a useful early marker of cognitive decline,” she said.
“OCT is increasingly widespread in optometric and ophthalmic clinics. It is relatively inexpensive, takes a few seconds to conduct, and is comfortable for the patient. As such, it has a high potential as a screening tool,” she told MedPage Today.
In the U.K. Biobank study, 32,038 people without a neurodegenerative disease were included at baseline testing; their average age was 56 and 53.6% were women. Those in the thinnest quintile of RNFL were 11% more likely to fail at least on3 cognitive test. When 1,251 people completed follow-up cognitive tests 3 years later, those with an RNFL thickness in the two thinnest quintiles were almost twice as likely to have at least 1 worse test score (quintile 1: OR 1.92; quintile 2: OR 2.08; P<0.001 for both).
“The size of our study gave us unparalleled statistical power, and we believe this now confirms the link between thinner RNFL and very early cognitive weaknesses, and subtle future changes, in the general population,” Foster said.
The Rotterdam Study also revealed eye-related associations in 3,289 people with an average age of 69, of whom 41 (1.2%) already had dementia at baseline. While thinner ganglion cell–inner plexiform layer (GC-IPL) was associated with prevalent dementia (OR per SD decrease in GC-IPL 1.37), RFNL was not.
Over an average follow-up of 4.5 years, 86 people (2.6%) developed dementia, mostly Alzheimer’s disease. Thinner RNFL at baseline was associated with an increased risk of developing dementia (HR per SD decrease in RNFL 1.44; similar for Alzheimer’s disease), but no link was seen between GC-IPL thickness and incident dementia (HR 1.13).
Brain scans and spinal taps show it may be possible to detect Alzheimer’s early, but “given these are costly and painful, doctors are understandably reluctant to use them widely,” Nguyen observed. “What’s needed is an early, easy and cheap method to detect Alzheimer’s disease.”
While OCT may help fill this gap, “the challenge with the technology and the marker to retinal nerve fiber layer thinning is the lack of specificity for Alzheimer’s disease, as other diseases such as glaucoma also exhibit these changes,” she pointed out.
Extrapolating these findings to clinical practice should be approached cautiously, Foster noted. “There may be a role for population-wide screening with either a broad or narrow focus,” he said. And cognitive decline is an emotive subject, he noted. “People who previously thought themselves healthy may feel labeled as ‘early dementia’ or ‘high risk for dementia,’ and this may have significant, adverse psychological impact.”
There’s no systemic disease that doesn’t have an eye sign, he added. “Retinal morphometry, either of vessels or neuroretina, can contribute to risk profiling for stroke, myocardial infarction, hypertension, diabetes, and dementia. These tests currently are limited to the research arena, but are likely to become available to general practitioners within 5 years.”
The UK Biobank analysis was supported by the Eranda Foundation via the International Glaucoma Association.
Foster disclosed no relevant relationships with Allergan, Carl Zeiss, Google/DeepMind, and Santen, as well as support from Alcon and the Richard Desmond Charitable Trust/Fight for Sight. Co-authors disclosed multiple relevant relationships with industry.
The Rotterdam Study was funded by Erasmus Medical Center and Erasmus University, the Netherlands Organization for the Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health,Welfare and Sports, the European Commission, and the Municipality of Rotterdam.
Ikram and co-authors disclosed no relevant relationships with industry.
Primary Source
JAMA Neurology
Secondary Source
JAMA Neurology
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