Eyetracking Metrics in Young Onset Alzheimer’s Disease: A Window into Cognitive Visual Functions

Young onset Alzheimer’s disease (YOAD) is defined as symptom onset before the age of 65 years and is particularly associated with phenotypic heterogeneity. Atypical presentations, such as the clinic-radiological visual syndrome posterior cortical atrophy (PCA), often lead to delays in accurate diagnosis. Eyetracking has been used to demonstrate basic oculomotor impairments in individuals with dementia. In the present study, we aim to explore the relationship between eyetracking metrics and standard tests of visual cognition in individuals with YOAD. Fifty-seven participants were included: 36 individuals with YOAD (n =  26 typical AD; n =  10 PCA) and 21 age-matched healthy controls. Participants completed three eyetracking experiments: fixation, pro-saccade, and smooth pursuit tasks. Summary metrics were used as outcome measures and their predictive value explored looking at correlations with visuoperceptual and visuospatial metrics. Significant correlations between eyetracking metrics and standard visual cognitive estimates are reported. A machine-learning approach using a classification method based on the smooth pursuit raw eyetracking data discriminates with approximately 95% accuracy patients and controls in cross-validation tests. Results suggest that the eyetracking paradigms of a relatively simple and specific nature provide measures not only reflecting basic oculomotor characteristics but also predicting higher order visuospatial and visuoperceptual impairments. Eyetracking measures can represent extremely useful markers during the diagnostic phase and may be exploited as potential outcome measures for clinical trials

ApoE influences regional white-matter axonal density loss in Alzheimer's disease

Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOEε4 status is associated with different patterns of white-matter neurodegeneration

Navigational cue effects in Alzheimer's disease and posterior cortical atrophy.

OBJECTIVE: Deficits in spatial navigation are characteristic and disabling features of typical Alzheimer's disease (tAD) and posterior cortical atrophy (PCA). Visual cues have been proposed to mitigate such deficits; however, there is currently little empirical evidence for their use. METHODS: The effect of visual cues on visually guided navigation was assessed within a simplified real-world setting in individuals with tAD (n = 10), PCA (n = 8), and healthy controls (n = 12). In a repeated-measures design comprising 36 trials, participants walked to a visible target destination (an open door within a built environment), with or without the presence of an obstacle. Contrast and motion-based cues were evaluated; both aimed to facilitate performance by applying perceptual changes to target destinations without carrying explicit information. The primary outcome was completion time; secondary outcomes were measures of fixation position and walking path directness during consecutive task phases, determined using mobile eyetracking and motion capture methods. RESULTS: Results illustrate marked deficits in patients' navigational ability, with patient groups taking an estimated two to three times longer to reach target destinations than controls and exhibiting tortuous walking paths. There were no significant differences between tAD and PCA task performance. Overall, patients took less time to reach target destinations under cue conditions (contrast-cue: 11.8%; 95% CI: [2.5, 20.3]) and were more likely initially to fixate on targets. INTERPRETATION: The study evaluated navigation to destinations within a real-world environment. There is evidence that introducing perceptual changes to the environment may improve patients' navigational ability

Feasibility Study of Dual Energy Radiographic Imaging for Target Localization in Radiotherapy for Lung Tumors

Purpose Dual-energy (DE) radiographic imaging improves tissue discrimination by separating soft from hard tissues in the acquired images. This study was to establish a mathematic model of DE imaging based on intrinsic properties of tissues and quantitatively evaluate the feasibility of applying the DE imaging technique to tumor localization in radiotherapy. Methods We investigated the dependence of DE image quality on the radiological equivalent path length (EPL) of tissues with two phantoms using a stereoscopic x-ray imaging unit. 10 lung cancer patients who underwent radiotherapy each with gold markers implanted in the tumor were enrolled in the study approved by the hospital's Ethics Committee. The displacements of the centroids of the delineated gross tumor volumes (GTVs) in the digitally reconstructed radiograph (DRR) and in the bone-canceled DE image were compared with the averaged displacements of the centroids of gold markers to evaluate the feasibility of using DE imaging for tumor localization. Results The results of the phantom study indicated that the contrast-to-noise ratio (CNR) was linearly dependent on the difference of EPL and a mathematical model was established. The objects and backgrounds corresponding to ΔEPL less than 0.08 are visually indistinguishable in the bone-canceled DE image. The analysis of patient data showed that the tumor contrast in the bone-canceled images was improved significantly as compared with that in the original radiographic images and the accuracy of tumor localization using the DE imaging technique was comparable with that of using fiducial makers. Conclusion It is feasible to apply the technique for tumor localization in radiotherapy

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Corals record long-term Leeuwin current variability including Ningaloo Niño/Niña since 1795

Variability of the Leeuwin current (LC) off Western Australia is a footprint of interannual and decadal climate variations in the tropical Indo-Pacific. La Niña events often result in a strengthened LC, high coastal sea levels and unusually warm sea surface temperatures (SSTs), termed Ningaloo Niño. The rarity of such extreme events and the response of the southeastern Indian Ocean to regional and remote climate forcing are poorly understood owing to the lack of long-term records. Here we use well-replicated coral SST records from within the path of the LC, together with a reconstruction of the El Niño-Southern Oscillation to hindcast historical SST and LC strength from 1795 to 2010. We show that interannual and decadal variations in SST and LC strength characterized the past 215 years and that the most extreme sea level and SST anomalies occurred post 1980. These recent events were unprecedented in severity and are likely aided by accelerated global ocean warming and sea-level rise. © 2014 Macmillan Publishers Limited

Coral record of southeast Indian Ocean marine heatwaves with intensified Western Pacific temperature gradient

Increasing intensity of marine heatwaves has caused widespread mass coral bleaching events, threatening the integrity and functional diversity of coral reefs. Here we demonstrate the role of inter-ocean coupling in amplifying thermal stress on reefs in the poorly studied southeast Indian Ocean (SEIO), through a robust 215-year (1795-2010) geochemical coral proxy sea surface temperature (SST) record. We show that marine heatwaves affecting the SEIO are linked to the behaviour of the Western Pacific Warm Pool on decadal to centennial timescales, and are most pronounced when an anomalously strong zonal SST gradient between the western and central Pacific co-occurs with strong La Niña's. This SST gradient forces large-scale changes in heat flux that exacerbate SEIO heatwaves. Better understanding of the zonal SST gradient in the Western Pacific is expected to improve projections of the frequency of extreme SEIO heatwaves and their ecological impacts on the important coral reef ecosystems off Western Australia

The Genotype Specific Competitive Ability Does Not Correlate with Infection in Natural Daphnia magna Populations

Different evolutionary hypotheses predict a correlation between the fitness of a genotype in the absence of infection and the likelihood to become infected. The cost of resistance hypothesis predicts that resistant genotypes pay a cost of being resistant and are less fit in the absence of parasites. The inbreeding-infection hypothesis predicts that the susceptible individuals are less fit due to inbreeding depression.Here we tested if a host's natural infection status was associated with its fitness. First, we experimentally confirmed that cured but formerly infected Daphnia magna are genetically more susceptible to reinfections with Octosporea bayeri than naturally uninfected D. magna. We then collected from each of 22 populations both uninfected and infected D. magna genotypes. All were treated against parasites and kept in their asexual phase. We estimated their relative fitness in an experiment against a tester genotype and in another experiment in direct competition. Consistently, we found no difference in competitive abilities between uninfected and cured but formerly infected genotypes. This was the case both in the presence as well as in the absence of sympatric parasites during the competition trials.Our data do not support the inbreeding-infection hypothesis. They also do not support a cost of resistance, however ignoring other parasite strains or parasite species. We suggest as a possible explanation for our results that resistance genes might segregate largely independently of other fitness associated genes in this system