A new study has found that thinning of the eye’s macular retinal nerve fiber layer (RNFL) is linked to cognitive decline in older adults.
Results from a study of more than 400 adults showed an association between primary macular RNFL thickness and scores on two cognitive tests – with thinner primary macular RNFL associated with greater cognitive decline.
Sharp lower cognitive scores and a higher prevalence of cognitive impairment and Alzheimer’s disease (AD) were also shown in participants whose total baseline macular RNFL thickness was below the lowest interquartile value versus participants with RNFL thickness above that threshold.
“In this study, RNFL macular thickness can be used as a predictive biomarker of long-term cognitive decline in adults 60 and older,” according to researchers led by Hyeong Min Kim, MD, Seoul National University School of Medicine, Seoul National University Hospital Bundang, Seongnam, Korea, Type.
The results were published online on May 26 in Gamma Ophthalmology.
Subjective, or preclinical, cognitive decline is preceded by mild cognitive impairment (MCI) and Alzheimer’s disease. Because of this, clinicians and researchers “have investigated several biomarkers of Alzheimer’s disease to diagnose the disease as early as possible,” the investigators note.
These include the discovery of non-invasive ocular biomarkers that may identify patients with cognitive impairment and Alzheimer’s disease. Since the publication of a 2001 study reporting thinning of the alveoli in Alzheimer’s patients, other studies have reported similar findings and improvements in perception.
In addition, segmentation of retinal layer structures by optical tomography (OCT) may “provide better opportunities to analyze retinal layer morphology in vivo,” the researchers wrote.
In the current study, they considered both transverse and longitudinal parameters of retinal layer thickness and their potential association with future cognitive decline and Alzheimer’s disease.
The researchers evaluated 430 randomly selected adults (mean age, 76.3 years; 48.6% women) from two population-based longitudinal cohort studies: the Korean Longitudinal Study on Health and Aging and the Longitudinal Study on Cognitive Aging and Dementia. Of these participants, 215 participants completed a median of 5.4 years of follow-up.
Spectral domain OCT was used to assess the thickness of the six retinal layers of the macular region, RNFLs, and sub-choroid. In addition, participants completed two neuropsychological assessments at baseline and at follow-up: the Korean version of Consortium to Create a Registry for Alzheimer’s Disease Assessment Package (CERAD-K) and the Mini-Mental State Examination (MMSE).
The variables included age, gender, education level, and the presence of APOE The e4 allele, diabetes and hypertension.
Baseline overall RNFL thickness was correlated with scores in both cognitive assessments at baseline.
|evaluation tool||Mathematics coefficient or degree[β](95% CI)||s Values|
|Sirad-K||.077 (.054 – .100)||.04|
|MMSE||.082 (.063 – .101)||.03|
|CI = confidence interval|
The same baseline correlations were demonstrated between RNFL thickness and both assessment tools for external and internal RNFL macular thickness.
However, in the longitudinal study, RNFL macular thickness was not associated with a decrease in CERAD or MMSE scores during the follow-up period.
However, when the researchers defined the cut-off value as the lowest quartile (less than 231 mm total RNFL thickness), they found that participants with the thinnest baseline total macular RNFL thickness had the largest reduction in CERAD and MMSE scores during the follow-up period. (s = .003 and s = .01, respectively) compared to those exceeding this limit. The same result is proven with outer and inner RNFL macular thickness.
Changes in the prevalence of MCI and AD from baseline to follow-up in the lowest and highest-lowest quartiles (n = 55 and n = 160, respectively) are shown in the table below.
|my quarter||MCI . Spread||AD spread|
|less than the lowest||
Follow up: 41.8%
Follow up: 10.9%
|above the lowest||
Follow up: 9.4%
Follow up: 1.9%
No differences were found in the relationship between cognitive score and RNFL thickness according to APOE e4 mode.
The investigators noted several limitations of the study. For example, only half of the primary participants persisted in the follow-up phase, which may have influenced the results of the longitudinal analysis. They also wrote that the follow-up period lasted only about 5 years, “a very short period of time in the development of neurodegenerative diseases.”
However, the study revealed that “basic RNFL macular thickness measured with OCT technology was associated with future cognitive decline,” they add.
The researchers suggest that “thinner macular RNFL may predict decline in cognitive performance” and “Macular RNFL thickness may be considered as a noninvasive ocular biomarker to assess changes in cognitive function in patients.”
However, further population-based investigations with long-term follow-up are necessary, they wrote.
Inexpensive and non-invasive
Comment on Medscape Medical NewsThere is now “a lot” of interest in retinal imaging as a technology for detecting early-stage Alzheimer’s disease, said Howard Villette, MD, MD and chief science officer of the Alzheimer’s Drug Discovery Foundation and professor of geriatrics, palliative care, medicine and neuroscience at Icahn College of Medicine at Mount Sinai in New York. “.
He noted that the current researchers evaluated the retinal layer, which is particularly inhabited by neurons and nerve fibers surrounding the granule, which come from the brain.
“So it makes sense and is plausible that what’s happening in the retinal layer reflects neurodegeneration in the brain,” said Villette, who was not involved in the research, and this was outlined in the study.
OCT is commonly used in ophthalmic practice, but not for the purpose described in this study.
There are other, more advanced techniques under investigation that may be able to detect amyloid and use it as add-ons to OCT devices, such as hyperspectral camera imaging, which may “find its place in the algorithm” for diagnosing Alzheimer’s disease, Villette said.
“Imagine a world in which older adults who go for their annual eye exam can have a 5- to 10-minute check for Alzheimer’s disease. Or, if they already have memory problems, an Alzheimer’s diagnosis can be confirmed based on the presence of amyloid plaques in,” Villette said. back of the eye.” He added that while the technology is not currently available in mainstream clinical practice, it is when it is “relatively inexpensive and noninvasive.”
In an accompanying editorial, Rajendra Apte, MD, PhD, professor of ophthalmology and visual sciences and vice president of innovation and translation, Washington University School of Medicine, St. with the development of cognitive impairment and dementia.”
Gamma Ophthalmology. Published online May 26, 2022. Abstract, Editorial
This research was supported by a research grant from Seoul National University Bundang Hospital, a National Research Foundation grant funded by the Korean government, and a grant from the Korean Health Technology Research and Development Project, Ministry of Health and Welfare, Republic of Korea. Investigators and Fillit reported no related financial relationships. The Alzheimer’s Drug Discovery Foundation invests in retina programs but was not involved in this study. Apte stated that it has received research funding, funding from the Department of Ophthalmology from the Jeffrey Fort Innovation Fund and the Star Foundation, and an unrestricted grant from the Research to Prevent Blindness Foundation.
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