Computer-based Eye-tracking Analysis of King-Devick Test Differentiates Persons with Idiopathic Normal Pressure Hydrocephalus from Cognitively Unimpaired

Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.Background: Functional defects in eye movements and reduced reading speed in neurodegenerative diseases represent a potential new biomarker to support clinical diagnosis. We investigated whether computer-based eye-tracking (ET) analysis of the King-Devick (KD) test differentiates persons with idiopathic normal pressure hydrocephalus (iNPH) from cognitively unimpaired [control (CO)] and persons with Alzheimer's disease (AD). Methods: We recruited 68 participants (37 CO, 10 iNPH, and 21 AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating interview. The KD reading test was performed using computer-based ET. We analyzed the total time used for the reading test, number of errors, durations of fixation and saccade, and saccade amplitudes. Results: The iNPH group significantly differed from the CO group in the KD test mean total time (CO 69.3 s, iNPH 87.3 s; P≤0.009) and eye-tracking recording of the mean saccade amplitude (CO 3.6 degree, iNPH 3.2 degree; P≤0.001). The AD group significantly differed from the CO group in each tested parameter. No significant differences were detected between the iNPH and AD groups. Conclusion: For the first time, we demonstrated altered reading ability and saccade amplitudes in patients with iNPH.Peer reviewe

Shortening of Saccades as a Possible Easy-to-Use Biomarker to Detect Risk of Alzheimer's Disease

Background: Wide-ranging functional defects in eye movements have been reported in Alzheimer's disease (AD) dementia. The detection of abnormal eye movements and reading problems may identify persons at risk of AD when clear clinical symptoms are lacking. Objective: To examine whether computer-based eye-tracking (ET) analysis of King-Devick (KD) test results differentiates cognitively healthy persons from persons with minor problems in cognitive testing or diagnosed mild AD. Methods: We recruited 78 participants (57 non-demented, 21 with mild AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating (CDR) interview. The non-demented participants were further divided into control (normal CERAD subtests, mean MMSE= 28) and objective mild cognitive impairment (MCI; decline in at least one CERAD memory score, mean MMSE= 27) groups. The KD reading test was performed using computer-based ET. The total time used for the reading test, errors made, fixation and saccade durations, and saccade amplitudes were analyzed. Results: We found significant differences between the control, objective MCI, and AD groups in regard to the mean saccade amplitude (3.58, 3.33, and 3.21 ms, respectively, p < 0.03) and duration (27.1, 25.3, and 24.8 ms, respectively, p < 0.05). The KD error scores in the AD group differed significantly (p < 0.01) from the other groups. Conclusion: Computed ET analysis of the KD test may help detect persons with objective MCI early when clear clinical symptoms are lacking. The portable device for ET is easy to use in primary health care memory clinics.Peer reviewe

Biometal Dyshomeostasis in Olfactory Mucosa of Alzheimer's Disease Patients

Olfactory function, orchestrated by the cells of the olfactory mucosa at the rooftop of the nasal cavity, is disturbed early in the pathogenesis of Alzheimer's disease (AD). Biometals including zinc and calcium are known to be important for sense of smell and to be altered in the brains of AD patients. Little is known about elemental homeostasis in the AD patient olfactory mucosa. Here we aimed to assess whether the disease-related alterations to biometal homeostasis observed in the brain are also reflected in the olfactory mucosa. We applied RNA sequencing to discover gene expression changes related to metals in olfactory mucosal cells of cognitively healthy controls, individuals with mild cognitive impairment and AD patients, and performed analysis of the elemental content to determine metal levels. Results demonstrate that the levels of zinc, calcium and sodium are increased in the AD olfactory mucosa concomitantly with alterations to 17 genes related to metal-ion binding or metal-related function of the protein product. A significant elevation in alpha-2-macroglobulin, a known metal-binding biomarker correlated with brain disease burden, was observed on the gene and protein levels in the olfactory mucosa cells of AD patients. These data demonstrate that the olfactory mucosa cells derived from AD patients recapitulate certain impairments of biometal homeostasis observed in the brains of patients.Peer reviewe

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

Objective To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population. Methods Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR. Results The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p <0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers. Conclusions This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.Peer reviewe

Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients

Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. Olfactory dysfunction manifests early in several neurodegenerative disorders including Alzheimer's disease, however, disease-related alterations to the olfactory mucosal cells remain poorly described. The aim of this study was to evaluate the olfactory mucosa differences between cognitively healthy individuals and Alzheimer's disease patients. We report increased amyloid-beta secretion in Alzheimer's disease olfactory mucosal cells and detail cell-type-specific gene expression patterns, unveiling 240 differentially expressed disease-associated genes compared to the cognitively healthy controls, and five distinct cell populations. Overall, alterations of RNA and protein metabolism, inflammatory processes, and signal transduction were observed in multiple cell populations, suggesting their role in Alzheimer's disease-related olfactory mucosa pathophysiology. Furthermore, the single-cell RNA-sequencing proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. Our results reveal disease-related changes of olfactory mucosal cells in Alzheimer's disease and demonstrate the utility of single-cell RNA sequencing data for investigating molecular and cellular mechanisms associated with the disease.Peer reviewe

Mobile mapping of night-time road environment lighting conditions

The measurement of 3D geometry for road environments is one of the main applications of mobile mapping systems (MMS). We present mobile mapping applied to a night-time road environment. We integrate the measurement of luminances into a georeferenced 3D point cloud. The luminance measurement and the 3D point cloud acquired with an MMS are used in assessing road environment lighting conditions. Luminance (cd/m2) was measured with a luminance-calibrated panoramic camera system, and point cloud was produced by laser scanners. The relative orientation between the GNSS, IMU, camera, and laser scanner sensors was solved in order to integrate the data sets into the same coordinate system. Hence, the georeferenced luminance values are transferable into geographic information systems (GIS). The method provides promising results for future road lighting assessment. In addition, this article demonstrates the night-time mobile mapping principle applied to a road section in Helsinki, Finland. Finally, we discuss the futureapplications of mobile-mapped luminance point clouds.Peer reviewe

Preregistration classification of mobile LIDAR data using spatial correlations

We explore a novel paradigm for light detection and ranging (LIDAR) point classification in mobile laser scanning (MLS). In contrast to the traditional scheme of performing classification for a 3-D point cloud after registration, our algorithm operates on the raw data stream classifying the points on-the-fly before registration. Hence, we call it preregistration classification (PRC). Specifically, this technique is based on spatial correlations, i.e., local range measurements supporting each other. The proposed method is general since exact scanner pose information is not required, nor is any radiometric calibration needed. Also, we show that the method can be applied in different environments by adjusting two control parameters, without the results being overly sensitive to this adjustment. As results, we present classification of points from an urban environment where noise, ground, buildings, and vegetation are distinguished from each other, and points from the forest where tree stems and ground are classified from the other points. As computations are efficient and done with a minimal cache, the proposed methods enable new on-chip deployable algorithmic solutions. Broader benefits from the spatial correlations and the computational efficiency of the PRC scheme are likely to be gained in several online and offline applications. These range from single robotic platform operations including simultaneous localization and mapping (SLAM) algorithms to wall-clock time savings in geoinformation industry. Finally, PRC is especially attractive for continuous-beam and solid-state LIDARs that are prone to output noisy data.Peer reviewe

Comparison of the Selected State-Of-The-Art 3D Indoor Scanning and Point Cloud Generation Methods

Accurate three-dimensional (3D) data from indoor spaces are of high importance for various applications in construction, indoor navigation and real estate management. Mobile scanning techniques are offering an efficient way to produce point clouds, but with a lower accuracy than the traditional terrestrial laser scanning (TLS). In this paper, we first tackle the problem of how the quality of a point cloud should be rigorously evaluated. Previous evaluations typically operate on some point cloud subset, using a manually-given length scale, which would perhaps describe the ranging precision or the properties of the environment. Instead, the metrics that we propose perform the quality evaluation to the full point cloud and over all of the length scales, revealing the method precision along with some possible problems related to the point clouds, such as outliers, over-completeness and misregistration. The proposed methods are used to evaluate the end product point clouds of some of the latest methods. In detail,point clouds are obtained from five commercial indoor mapping systems, Matterport, NavVis, Zebedee, Stencil and Leica Pegasus: Backpack, and three research prototypes, Aalto VILMA, FGI Slammer and the Wurzburg backpack. These are compared against survey-grade TLS point clouds captured from three distinct test sites that each have different properties. Based on the presented experimental findings, we discuss the properties of the proposed metrics and the strengths and weaknesses of the above mapping systems and then suggest directions for future research.Peer reviewe