Macular RNFL thickness flags future cognitive decline in older Asians

Macular retinal nerve fibre layer (RNFL) thickness appears to be a useful prognostic biomarker of long-term cognitive decline in older adults, a study from Korea has found.

In an exploratory cross-sectional analysis, “[w]e found that only the macular RFNL was associated with neuropsychiatric test scores and that it could be a candidate layer for predicting cognitive decline,” according to researchers from Seoul National University Bundang Hospital, Seongnam, South Korea, headed by Dr Hyeong Min Kim.

Specifically, baseline macular RNFL thickness assessed using spectral-domain optical coherence tomography (OCT) correlated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) score (coefficient [β], 0.077, 95 percent confidence interval [CI], 0.054–0.100; p=0.04 for total macular area) and the Mini-Mental State Examination (MMSE) score (coefficient [β], 0.082, 95 percent CI, 0.063–0.101; p=0.03 for total macular area). [JAMA Ophthalmol 2022;doi:10.1001/jamaophthalmol.2022.1563]

Among 430 community-dwelling participants (mean age 76.3 years, 48.6 percent women), those who were in the lowest quartile of total macular RNFL thickness (231 μm) showed a larger decline in the CERAD and MMSE scores over a mean follow-up of 5.4 years (p=0.003 and p=0.01, respectively).

Furthermore, participants with baseline total macular RNFL thickness <231 μm exhibited a much greater drop in cognitive scores and a higher prevalence of cognitive impairment and Alzheimer’s disease (AD) than those whose RNFL thickness was above the lowest quartile cutoff value.

In light of the findings, Kim and colleagues proposed “that a thinner macular RNFL may predict a decline in cognitive performance.”

Useful in clinical practice?

“Overall, macular RNFL thickness may be considered a noninvasive ocular biomarker for assessing changes in cognitive function in patients,” Kim stated.

“The participants of the current study were community-based people [aged] 60 years and older; thus, unlike in prior investigations, most participants presented with normal cognitive function or mild cognitive impairment, with only 12 patients (2.8 percent) having definite AD. Therefore, we considered our cohort population suitable for assessing the association between retinal layer thickness and cognitive function in a real-world clinical setting,” he said.

Kim mentioned other merits to the study, including the assessment of both cognitive function scores (CERAD and MMSE) and the performance of a “more comprehensive statistical analysis” by adjusting for variables that might affect cognitive function assessment (ie, age, sex, education level, diabetes, hypertension, and APOE ε4 status). He also pointed out that they investigated the possibility of predicting cognitive function decline based on baseline retinal layer thickness in a longitudinal study.

“Hence, our results could be useful for clinicians, both neuropsychiatrists and ophthalmologists, in matching OCT retinal thickness data and MMSE scores in the real world,” Kim said.

However, he admitted that they were not able to perform β-amyloid (Aβ) positron emission tomography and magnetic resonance imaging, given that cerebral Aβ deposition can begin around 15–20 years before the onset of AD, which is crucial for detecting future candidates for AD who are still cognitively healthy.

Having said that, Kim called for further population-based investigations with a long-term follow-up.