Macular Retinal Nerve Fiber Layer Thickness May Be Biomarker for Cognitive Decline

Se Joon Woo, MD, PhD

New research found that optical coherence tomography (OCT) measured baseline macular retinal nerve fiber layer (RNFL) thickness was associated with future cognitive decline in older individuals.

“Overall, macular RNFL thickness may be considered a noninvasive ocular biomarker for assessing changes in cognitive function in patients,” wrote study authors Se Joon Woo, MD, PhD, Department of Ophthalmology and Ki Woong Kim, MD, PhD, Department of Neuropsychiatry, Seoul National University Bundang Hospital.

The community-based longitudinal cohort study conducted in Korea looked to enroll a larger number of individuals to determine the association between retinal layer thickness and cognitive function in healthy individuals and those with cognitive impairment.

They enrolled adults 60 years and older from 2 population-based longitudinal cohort studies, including the Korean Longitudinal Study on Health and Aging (KLoSHA) and the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD).

From a total of 500 individuals enrolled, 70 patients were excluded due to high myopia (axial length >26 mm), high intraocular pressure (>21 mm Hg), self-reported glaucoma history, and combined ocular pathologies that might affect retinal layer thickness, including age-related macular degeneration and diabetic macular edema found on OCT infrared imaging. .

Then, among this population, a total of 215 patients completed follow-up assessments with a mean follow-up duration of 5.4 years. The baseline assessment was conducted from September 2010 to September 2011 with the follow-up from September 2015 to September 2016. They utilized spectral-domain optical coherence tomography to assess the thickness of 6 retinal layers in the macular region, the papillary retinal nerve fiber layer (RNFLs), and the subfoveal cohorid.

Investigators examined the association between baseline retinal layer thickness and baseline cognitive test scores using multiple linear regression analyses and change in cognitive test scores using repeated-measures analysis of variance.

Data show the baseline macular RNFL thickness was associated with baseline Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) score (coefficient [β] = 0.077; 95% CI, 0.054 - 0.100; P = .04 for total macular area) and Mini-Mental State Examination (MMSE) score (coefficient [β] = 0.082; 95% CI, 0.063-0.101; P = .03 for total macular area).

Investigators noted a thinner baseline total macular RNFL thickness (lowest quartile, <231 μm) was associated with a larger decline in CERAD and MMSE scores throughout the follow-up period (P = .003 and P = .01, respectively).

Furthermore, participants with baseline total macular RNFL thickness below the lowest quartile cutoff value presented a greater decline in cognitive scores and a higher prevalence of cognitive impairment and Alzheimer disease than those with RNFL thickness above the lowest quartile cutoff value.

Within the lower-quartile group, the prevalence of mild cognitive impairment increased from baseline from 27.2% to 41.8% and the prevalence of Alzheimer disease increased from 7.2% to 10.9% at follow-up. Moreover, in the above- lowest-quartile group, the prevalence of mild cognitive impairment increased from 6.3% to 9.4% for mild cognitive impairment and from 1.3% to 1.9% for Alzheimer disease at follow-up.

Investigators noted that the convenience of the MMSE test to diagnose cognitive impairment in a cognitive setting outweighs its disadvantages, including limited examination of visuospatial cognitive ability,

“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,” the study authors concluded.

The study, “Association Between Retinal Layer Thickness and Cognitive Decline in Older Adults,” was published in JAMA Ophthalmology.