Reading cognition from the eyes—association of retinal nerve fiber layer thickness with cognitive performance in a population-based study
Authors: Girbardt Johanna , Luck Tobias , Kynast Jana , Rodriguez Francisca S , Wicklein Barbara , Wirkner Kerstin , Engel Christoph , Girbardt Christian , Wang Mengyu , Polyakova Maryna , Witte A Veronica , Loeffler Markus , Villringer Arno , Riedel-Heller Steffi G , Schroeter Matthias L , Elze Tobias , Rauscher Franziska G 
Published: November 2021

Abstract
With the eye as window to the brain, non-invasive fast screening of retinal nerve fiber layer thickness poses the opportunity for early detection of cognitive decline leading to dementia.
Our objective is to determine whether performance in various neurocognitive tests has an association with itemized retinal nerve fiber layer thickness. Detailed investigation of associations factored in sex and eye-side.
The large population-based LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was conducted at Leipzig University, Germany from 2011 to 2014. Randomly selected participants (N = 10,000) were drawn from population registry in an age- and gender-stratified manner, focusing on 40–80 years.
Cognitive function was examined with the CERAD-NP Plus test-battery (Consortium to Establish a Registry for Alzheimer's Disease), Stroop-Test, Reading the Mind in the Eyes-Test, Multiple-Choice Vocabulary Intelligence Test.
Circumpapillary retinal nerve fiber layer thickness was measured with Optical Coherence Tomography. Subjects with reliable measurements (≥50 B-scan repetitions, signal-to-noise-ratio ≥20 dB, ≤5% missing A-scans) and without clinical eye pathology (sample A) and additional exclusion due to conditions of the central nervous system (sample B) were evaluated. The relationship between cognitive function and retinal nerve fiber layer thickness was investigated for six segments: temporal, temporal-superior, temporal-inferior, nasal, nasal-superior, nasal-inferior. For comparison with other studies, global mean is given. Brain-side projection analysis links results to corresponding brain hemisphere.
We analyzed 11,124 eyes of 6,471 subjects (55.5 years of age [19.1–79.8 years], 46.9% male). Low cognitive performance was predominantly associated with thinner retinal nerve fiber layer thickness. Correlation analysis indicated emphasis on global and temporally located effects. Multivariable regression analysis with adjustments (age, sex, scan radius) presented individual results for each test, differentiating between sex and eye-side. For instance verbal fluency tests and Trail-Making-Test-B show stronger association in females; Trail-Making-Test-A shows right-eye dominance. Findings in Trail-Making-Test-A projected to left brain-hemisphere, and the ratio incongruent to neutral in the Stroop test projected to right brain-hemisphere.
Separate assessment for sex and eye-side is presented for the first time in a population-based study. Location-specific sectorial retinal nerve fiber layer thickness was found to be an indicator for cognitive performance, giving an option for early detection of cognitive decline and the potential of early treatment.