The test-retest reliability of DR measurements in this study was very high. This was the case not only for DR-rich brain areas, but also for regions with low DR density. These results will provide a solid base for future joint PET/MRI data analyses in stimulation-dependent mapping of DR-containing neurons and their effects on projections in neuronal circuits that determine behavior.
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.
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 c...
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