Association of retinal fibre layer thickness with cognition in a population‐based study
Authors: Rauscher Franziska G. , Girbardt Johanna , Luck Tobias , Kynast Jana , Rodriguez Francisca S. , Witte A. Veronica , Wang Mengyu , Engel Christoph , Loeffler Markus , Villringer Arno , Riedel‐Heller Steffi G. , Schroeter Matthias L. , Elze Tobias 
Published: December 2022

Background: The retina is part of the central nervous system. Layers of the retina can be investigated non‐invasively by optical coherence tomography (OCT). Previously, associations of retinal nerve fibre layer thickness (RNFLT) with cognitive function were established in population‐based studies. Clinical relevance constitutes the improvement of early detection of dementia precursors.

Objectives: Investigate the relationship of RNFLT to cognitive function based on different neurocognitive testing procedures in a large population‐based sample.

Methods: Within the population‐based LIFE‐Adult study (Leipzig Research Center for Civilization Diseases; Germany), circumpapillary RNFLT was measured by spectral domain OCT (Heidelberg Engineering, Heidelberg). RNFLT was evaluated for subjects with reliable measurements (≥50 B‐scan repetitions, quality ≥20 dB, ≤5% missing A‐scans) and without clinical ocular pathology. The relationship between cognitive function and RNFLT was investigated for six sectors: temporal (T), temporal superior (TS), temporal inferior (TI), nasal (N), nasal superior (NS), nasal inferior (NS) and global mean (G). Neuropsychological questionnaires included single tests from the German version of the CERAD Neuropsychological Test Battery (Consortium to Establish a Registry for Alzheimer's Disease), Trail Making Test, Stroop‐Test, Reading the Mind in the Eyes‐Test and Multiple Choice Vocabulary Intelligence Test‐B. Cognitive function was additionally examined using the CERAD Boston Naming Test and CERAD Phonematic Fluid in people over 60 years of age.

Results: 5646 eyes of 5646 subjects were evaluated. After correction for multiple comparisons, statistically significant correlation with RNFLT was found for the CERAD test battery, Verbal Fluid Animals (T,TS), Word List Retrieval (G,T,TS,TI), and Word List Learning (G,T,TS,TI,NS). Furthermore, there was a correlation of RNFLT with the trail making test TMT‐A and TMT‐B (G,T,TS,TI). The Stroop‐neutral and Stroop‐incongruent condition (G,T,TS,TI,NS) and the vocabulary test (T,N,NS,NI) also showed a statistically significant association with RNFLT. The Reading the Mind in the Eyes test and some CERAD categories (Mini Mental Status Test (MMSE), Boston Naming Test, Figure Drawing, Figure Recall, Phonematic Fluid, Word List Recognition) did not correlate. Regression, after adjustment for age and refraction, presented with the following associations: TMT‐A (G,TS,TI), TMT‐B (G), Stroop incongruent condition (NS), vocabulary test (T).

Discussion: For LIFE‐Adult, cognitive function was correlated with RNFLT using CERAD word list learning, trail making test, Stroop test and vocabulary test. In comparison, subjects of the Rotterdam study with a thinner RNFLT showed an increased risk of developing dementia within a few years; furthermore, a correlation between RNFLT to MMSE and Stroop test was established. The Erasmus Rucphen Family study found an association of thicker RNFL with better cognitive function especially in subjects under 40 years of age; RNFLT correlated with TMT‐B. In the Three‐City‐Alienor study, it was shown that thicker RNFLT was associated with better cognitive function in the Free and Cued Selective Reminding Test; this was particularly true for temporal, superotemporal and inferotemporal segments.

Conclusions: Individual neurocognitive tests correlate with thickness differences in RNFLT. We found a thicker RNFLT associated with better cognitive function, while deficits in cognitive function were associated with a significantly thinner RNFLT.