Reading cognition from the eyes: Association of retinal nerve fiber layer thickness with cognitive performance in a population-based study

With the eye as a window to the brain, non-invasive fast screening of retinal nerve fibre 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 fibre 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 and Multiple-Choice Vocabulary Intelligence Test. Circumpapillary retinal nerve fibre 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 fibre layer thickness was investigated for six segments: temporal, temporal-superior, temporal-inferior, nasal, nasal-superior and nasal-inferior. For comparison with other studies, global mean is given. Brain-side projection analysis links results to the corresponding brain hemisphere. We analysed 11 124 eyes of 6471 subjects [55.5 years of age (19.1-79.8 years), 46.9% male]. Low cognitive performance was predominantly associated with thinner retinal nerve fibre layer thickness. Correlation analysis indicated emphasis on global and temporally located effects. Multivariable regression analysis with adjustments (age, sex and 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 fibre 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. The eye as a window to the brain was studied with optical coherence tomography and connected to cognition. Girbardt et al. report that thinner retinal nerve fibre layer thickness was found to be a meaningful index for poorer cognitive performance which presents the potential for prediction of future cognitive decline

Structural and Biophysical Insights into SPINK1 Bound to Human Cationic Trypsin

(1) The serine protease inhibitor Kazal type 1 (SPINK1) inhibits trypsin activity in zymogen granules of pancreatic acinar cells. Several mutations in the SPINK1 gene are associated with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). The most common variant is SPINK1 p.N34S. Although this mutation was identified two decades ago, the mechanism of action has remained elusive. (2) SPINK1 and human cationic trypsin (TRY1) were expressed in E. coli, and inhibitory activities were determined. Crystals of SPINK1–TRY1 complexes were grown by using the hanging-drop method, and phases were solved by molecular replacement. (3) Both SPINK1 variants show similar inhibitory behavior toward TRY1. The crystal structures are almost identical, with minor differences in the mutated loop. Both complexes show an unexpected rotamer conformation of the His63 residue in TRY1, which is a member of the catalytic triad. (4) The SPINK1 p.N34S mutation does not affect the inhibitory behavior or the overall structure of the protein. Therefore, the pathophysiological mechanism of action of the p.N34S variant cannot be explained mechanistically or structurally at the protein level. The observed histidine conformation is part of a mechanism for SPINK1 that can explain the exceptional proteolytic stability of this inhibitor

Retinal nerve fibre layer thickness reflects characteristics of brain grey and white matter

The retina is a relatively accessible part of the central nervous system compared to the brain. Using high resolution optical imaging we investigated the relationship between retinal thickness, obtained with optical coherence tomography, and structural features of the brain obtained with magnetic resonance imaging. In a population-based sample of over 500 subjects, we hypothesized: (i) that there are structural associations between circumpapillary retinal nerve fibre layer thickness and brain grey matter density and white matter microstructural properties in visual information processing areas, and specifically contralateral associations for nasal retinal fibers, and (ii) that retinal findings reflect broader changes in brain grey and white matter related to cardiovascular risk factors. In support of the first hypothesis, we showed associations of circumpapillary retinal nerve fibre layer thickness with visual cortex grey matter density and with optic radiation fractional anisotropy. These correlations were stronger for the right eye, possibly reflecting right ocular dominancy. Regarding the second hypothesis, while we confirmed the broad impact of cardiovascular risk factors such as body mass index, diabetes, and hypertension on brain structure, we didn’t find (adequate) significant partial correlations between circumpapillary retinal nerve fibre layer thickness and cardiovascular risk factors to support the hypothesis. As such, we couldn’t confirm that circumpapillary retinal nerve fibre layer thickness is associated with the impact of cardiovascular risk factors on the brain structure. However, when the effects of cardiovascular risk factors were accounted for statistically, circumpapillary retinal nerve fibre layer thickness (particularly on the right side) was associated with fractional anisotropy of limbic system tracts, i.e., the fornix and stria terminalis including hippocampus and amygdala. To further explore the structural associations between eye and brain, in terms of a possible common underlying pathology related to cardiovascular risk factors and progressive neurodegenerative diseases on the central nervous system, longitudinal and interventional studies are necessary

Ultrastructure of the Fungal Nucleus

The electron-dense material which regularly occurs at the poles of the nuclei of certain fungi during division has been studied in hyphal interphase nuclei of 4 basidio- and 3 ascomycetes. The shape of this material varies with the species and the nuclear age and may be that of a sphere or a dumbbell. In some instances paired diskoidal structures are found in the place of the globular elements of the dumbbell configuration. The organelle in question lies in an invagination of the nuclear envelope preferentially at the forward pointing pole of the nucleus. Its size (0.1-0.5 µm) is correlated with the size of the nucleus. In Polystictus versicolor the diameter of both globular elements of the polar organelle increases during initiation of the division process. The structure is identical with the fungal ‘centriole’ of light-microscopical studies but lacks the characteristic organization of a true centriole. It is suggested that the polar organelle is the equivalent of a kinetochore because it maintains continuous and direct contact with the nuclear envelope (on its cytoplasmic aspect), seems to be connected with the karyoplasm, exhibits oscillating movements, is continuous with microtubules during division and resembles in its fine structure the kinetochores of the chromosomes of higher plants and animals. In addition to its function as an organelle of nuclear motility it also seems to play a part in the initiation of DNA synthesis and nuclear division. If this is correct one would expect to find the genome of the fungal nucleus having the form of a unitary, coherent compound structure (chain) extending from or incorporating a single, solitary kinetochore.</jats:p