New research suggests that thinning of the macular retinal nerve (RNFL) fiber layer of the eye is related to cognitive decline in older adults.
The results of a study of more than 400 adults showed an association between the thickness of the initial macular RNFL and the scores on two cognitive tests, with a thinner-based macular RNFL associated with greater cognitive impairment.
There was also a more pronounced decline in cognitive scores and a higher prevalence of cognitive impairment and Alzheimer’s disease (AD) in participants with an initial total macular RNFL thickness below the lower quartile cut-off value compared to participants. with an RNFL thickness above this threshold.
“In this study, the thickness of macular RNFL could be used as a prognostic biomarker of long-term cognitive decline in adults aged 60 years or older,” said researchers led by Hyeong Min Kim, MD, College of Medicine. Seoul National University, Bundang Hospital of Seoul National University. , Seongnam, Korea, writes.
The findings were published online May 26 in JAMA Ophthalmology.
Early diagnosis
Subjective cognitive decline, or preclinical AD, precedes mild cognitive impairment (MCI) and AD. That’s why doctors and researchers “have investigated several AD biomarkers to diagnose the disease as soon as possible,” the researchers note.
These include the discovery of noninvasive ophthalmic biomarkers that could identify patients with cognitive impairment and AD. Since the publication of a 2001 study reporting peripapillary thinning of RNFL in patients with AD, other studies have reported similar findings and advances in visualization.
In addition, segmentation of retinal layer structures using optical coherence tomography (OCT) has “provided better opportunities to analyze retinal layer morphology in vivo,” the researchers write.
In the present study, they examined both cross-sectionally and longitudinally the retinal layer thickness parameters and their potential association with future cognitive decline and AD.
The researchers evaluated 430 randomly selected adults in the community (mean age, 76.3 years; 48.6% women) from two population-based longitudinal cohort studies: the Korean Longitudinal Study of Health and Aging and the Longitudinal study on cognitive aging and dementia. Of these participants, 215 completed an average of 5.4 years of follow-up.
Spectral domain OCT was used to assess the six-layer thickness of the retina of the macular region, the RNFL, and the subfoveal choroid. In addition, participants completed two neuropsychological assessments at baseline and follow-up: the Korean version of the Consortium to establish a Register for the Alzheimer’s Disease Assessment Package (CERAD-K) and the Mini-Examination of the Mental State (MMSE).
Covariates included age, sex, level of education, presence of the APOE e4 allele, diabetes, and hypertension.
Eye biomarker
The initial thickness of total macular RNFL was associated with scores on both baseline cognitive assessments.
Evaluation tool coefficient[β](95% CI) PER CERAD-K value 0.077 (0.054 – 0.100) 0.04 MMSE 0.082 (0.063 – 0.101) IC 0.03 = confidence interval
The same reference associations between RNFL thickness and both assessment tools remained valid for outer and inner macular RNFL thickness.
However, in the longitudinal study, macular RNFL thickness was not associated with decreases in CERAD or MMSE scores during the follow-up period.
However, when the researchers set the cut-off value as the lowest quartile (less than 231 mm total RNFL thickness), they found that participants with the thinnest initial total macular RNFL thickness had the largest decrease. of CERAD and MMSE scores during the follow-up period. (P = .003 and P = .01, respectively) compared to those above this threshold. The same finding was true with the thickness of the outer and inner macular RNFL.
The following table shows the changes in MCI and AD prevalence from baseline to follow-up in the lower and upper quartile groups (n = 55 in and 160, respectively).
Quartile MCI Prevalence AD Prevalence Below-minimum
reference: 27.2%
follow-up: 41.8%
base: 7.2%
follow-up: 10.9%
For over-minor
reference: 6.3%
follow-up: 9.4%
reference: 1.3%
follow-up: 1.9%
No differences were found in the association of cognitive score and RNFL thickness according to APOE e4 status.
Researchers note several limitations of the study. For example, only half of the initial participants continued with the follow-up phase, which could have affected the results of the longitudinal analysis. In addition, the follow-up period lasted only about 5 years, “which is a considerably short period of time in the development of neurodegenerative diseases,” they write.
However, the study revealed that “the thickness of the base macular RNFL measured with OCT was associated with future cognitive decline,” they add.
The researchers propose that “thinner macular RNFL may predict a decrease in cognitive performance” and “the thickness of macular RNFL may be considered a noninvasive ocular biomarker to assess changes in patients’ cognitive function.”
However, more population-based research is needed with long-term follow-up, they write.
Cheap, non-invasive
Commenting on Medscape Medical News, Howard Fillit, MD, co-founder and scientific director of the Alzheimer’s Drug Discovery Foundation and clinical professor of geriatric medicine and palliative care, medicine and neuroscience at The Icahn School of Medicine in Mount Sinai, New York, to say. There is now “a lot of interest in retinal imaging as a technology for detecting early-stage AD.”
Current researchers evaluated the layer of the retina of the eye, which is particularly populated by neurons and peripapillary nerve fibers, which come from the brain, he noted.
“It is therefore logical, plausible and reasonable that what is happening in the retinal layer of the eye reflects the neurodegeneration of the brain,” and this was shown in the study, said Fillit, who did not participate. in research.
OCT technology is commonly used in ophthalmic practice, but not for the purpose described in this study.
There are other more advanced technologies in research that can detect amyloid and be used as add-ons for OCT devices, such as hyperspectral camera imaging, which could “find its place in the algorithm” for diagnostics. AD, said Fillit.
“Imagine a world where older people who go for their annual eye exam could have a 5-10 minute scan to detect AD. Or, if they already have memory problems, a diagnosis of AD could be confirmed. from the presence of amyloid. plaques on the back of the eye, “Fillit said. While the technology is not currently available in regular clinical practice, it will be “relatively inexpensive and non-invasive,” he added.
In an attached editorial, Rajendra Apte, MD, PhD, Professor of Ophthalmology and Visual Sciences and Vice President of Innovation and Translation, Washington University School of Medicine, St. Louis, Missouri, writes that the study “contributes to our evolving knowledge of the ability of retinal imaging to identify biomarkers that predict the development of cognitive impairment and dementia.”
JAMA Ophthalmol. Published online May 26, 2022. Abstract, Editorial
This research was supported by a research grant from Bundang Hospital at Seoul National University, a grant from the National Research Foundation funded by the Korean government, and a grant from the Healthcare Technology R&D Project. of Korea, Ministry of Health and Welfare, Republic of Korea. The researchers and Fillit did not report any relevant financial reports. The Alzheimer’s Drug Discovery Foundation is investing in retinal programs, but did not participate in this study. Apt reportedly received research funding and funding from the Ophthalmology Department of the Jeffrey Fort Innovation Fund, the Starr Foundation, and an unrestricted grant from Research to Prevent Blindness.
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