The thinning of the retinal layer of the eye, a marker of cognitive decline?

Thinning of the macular retinal nerve fiber layer (RNFL) of the eye is linked to cognitive decline in older adults, new research suggests.

Results from a study of over 400 adults showed an association between baseline macular RNFL thickness and scores on two cognitive tests – with thinner baseline macular RNFL associated with greater cognitive decline.

A more pronounced decline in cognitive scores and a higher prevalence of cognitive impairment and Alzheimer’s disease (AD) were also shown in participants whose baseline total macular RNFL thickness was below the lowest quartile cut-off value compared to participants whose RNFL thickness was above this cut-off.

“In this study, macular RNFL thickness could be used as a prognostic biomarker for long-term cognitive decline in adults 60 years of age or older,” said researchers led by Hyeong Min Kim, MD, College of Medicine of Seoul National University, Seoul National University Bundang Hospital. , Seongnam, Korea, write.

The conclusions were published online May 26 at JAMA Ophthalmology.

Early diagnosis

Subjective cognitive decline, or preclinical AD, precedes mild cognitive impairment (MCI) and AD. For this reason, clinicians and researchers “studied several AD biomarkers to diagnose the disease as early as possible,” note the investigators.

These include the discovery of non-invasive ophthalmic biomarkers that could identify patients with cognitive impairment and Alzheimer’s disease. Since the publication of a 2001 study reporting peripapillary thinning of the RNFL in patients with AD, other studies have reported similar results and improvements in visualization.

Additionally, segmentation of retinal layer structures by optical coherence tomography (OCT) “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 parameters of retinal layer thickness and their potential association with future cognitive decline and AD.

Investigators evaluated 430 randomly selected community-dwelling adults (mean age, 76.3 years; 48.6% female) from two population-based longitudinal cohort studies: the Korean Longitudinal Health Study and aging and the longitudinal study of 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 thickness of six retinal layers of the macular region, RNFLs, and subfoveal choroid. In addition, participants completed two neuropsychological assessments at baseline and at follow-up: the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Package (CERAD-K) and the mini-examination of Alzheimer’s disease. mental state (MMSE).

Covariates included age, gender, level of education, presence of APOE e4 allele, diabetes and hypertension.

Ocular biomarker

Baseline macular RNFL total thickness was associated with scores on both cognitive assessments at baseline.

Assessment tool Coefficient[β](95% CI) P Assess
CERAD-K .077 (.054 – .100) .04
MSE .082 (.063 – .101) .03
CI = confidence interval

The same basic associations between RNFL thickness and both assessment tools held true for outer and inner macular RNFL thickness.

However, in the longitudinal study, macular RNFL thickness was not associated with a decrease in CERAD or MMSE scores during the follow-up period.

Nevertheless, when the researchers defined the cutoff 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 lowest greater decline in CERAD and MMSE scores during the follow-up period. (P = 0.003 and P = 0.01, respectively) compared to those above this threshold. The same finding was found to be true with outer and inner thickness of macular RNFL.

Changes in the prevalence of MCI and AD from baseline to follow-up in the lower quartile and upper quartile groups (n=55 and n=160, respectively) are shown in the table below.

Quartile MCI prevalence Prevalence of AD
below the lowest

benchmark: 27.2%

follow-up: 41.8%

baseline: 7.2%

tracking: 10.9%

above the low

baseline: 6.3%

tracking: 9.4%

baseline: 1.3%

tracking: 1.9%

No difference was found in the association of cognitive score and RNFL thickness according to APOE e4 status.

The investigators note several limitations of the study. For example, only half of the baseline participants continued to the follow-up phase, which may have affected the results of the longitudinal analysis. Furthermore, the follow-up period only lasted about 5 years, “which is a considerably short time period in the development of neurodegenerative diseases”, they write.

Nevertheless, the study found that “baseline macular RNFL thickness measured by OCT was associated with future cognitive decline,” they add.

The researchers propose that “thinner macular RNFL may predict decreased cognitive performance” and “macular RNFL thickness can be considered as a non-invasive ocular biomarker to assess changes in cognitive function in patients.”

However, further population-based surveys with long-term follow-up are needed, they write.

Inexpensive, non-invasive

Commenting for Medscape Medical NewsHoward 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 at Mount Sinai in New York, said he There is “a lot of interest now in retinal imaging as an early-stage AD detection technology.”

The current researchers assessed the retinal layer of the eye, which is particularly populated by neurons and peripapillary nerve fibers, which originate in the brain, he noted.

“So it’s logical, plausible and reasonable that what happens in the retinal layer of the eye reflects neurodegeneration in the brain,” and that was shown in the study, said Fillit, who was not involved. looking.

OCT technology is commonly used in ophthalmic practice, but not for the purpose described in this study.

There are other, more advanced technologies being investigated that may be able to detect amyloid and be used as complements to OCT devices, such as hyperspectral camera imaging, which may “find its way into the algorithm for AD diagnoses, Fillit said.

“Imagine a world where older people going for their annual eye exam could have a 5-10 minute exam to screen for Alzheimer’s disease. Or, if they already have memory problems, a diagnosis of Alzheimer’s disease. ‘Alzheimer’s could be confirmed based on the presence of amyloid plaques in the back of the eye,” Fillit said. Although the technology is not currently available in routine clinical practice, when it is , it will be “relatively inexpensive and non-invasive”, he added.

In a accompanying editorialRajendra Apte, MD, PhD, professor of ophthalmology and visual sciences and vice president for innovation and translation, Washington University School of Medicine, St. Louis, Missouri, writes that the study “contributes to the evolution our 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. Summary, Editorial

This research was supported by a research grant from the Bundang Hospital of Seoul National University, a grant from the National Research Foundation funded by the Korean government, and a grant from the Korea Technology R&D Project. Health, Ministry of Health and Welfare, Republic of Korea. Investigators and Fillit have not reported any relevant financial relationship. The Alzheimer’s Drug Discovery Foundation invests in retinal programs but did not participate in this study. Apte said he received research funding and funding from the Department of Ophthalmology from the Jeffrey Fort Innovation Fund, the Starr Foundation, and an unrestricted grant from Research to Prevent Blindness.

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