The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline.

BACKGROUND: Coronavirus disease 2019 (COVID-19), the far-reaching pandemic, has infected approximately 185 million of the world's population to date. After infection, certain groups, including older adults, men, and people of color, are more likely to have adverse medical outcomes. COVID-19 can affect multiple organ systems, even among asymptomatic/mild severity individuals, with progressively worse damage for those with higher severity infections. SUMMARY: The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily attaches to cells through the angiotensin-converting enzyme 2 (ACE2) receptor, a universal receptor present in most major organ systems. As SARS-CoV-2 binds to the ACE2 receptor, its bioavailability becomes limited, thus disrupting homeostatic organ function and inducing an injury cascade. Organ damage can then arise from multiple sources including direct cellular infection, overactive detrimental systemic immune response, and ischemia/hypoxia through thromboembolisms or disruption of perfusion. In the brain, SARS-CoV-2 has neuroinvasive and neurotropic characteristics with acute and chronic neurovirulent potential. In the cardiovascular system, COVID-19 can induce myocardial and systemic vascular damage along with thrombosis. Other organ systems such as the lungs, kidney, and liver are all at risk for infection damage. Key Messages: Our hypothesis is that each injury consequence has the independent potential to contribute to long-term cognitive deficits with the possibility of progressing to or worsening pre-existing dementia. Already, reports from recovered COVID-19 patients indicate that cognitive alterations and long-term symptoms are prevalent. This critical review highlights the injury pathways possible through SARS-CoV-2 infection that have the potential to increase and contribute to cognitive impairment and dementia.

Sequential-digital image correlation for mapping human posterior sclera and optic nerve head deformation.

Optic nerve head (ONH) deformations may be involved in the onset or further development of glaucoma, including in patients with relatively normal intraocular pressures (IOPs). Characterizing posterior scleral deformations over physiological pressures may provide a better understanding of how changes in IOP lead to changes in the mechanical environment of the ONH and possibly retinal ganglion cell death. Pressure inflation measurement test protocols are commonly used to measure deformation of the peripapillary sclera with full-field noncontact optical methods. The purpose of this work was to develop and validate a new sequential 3D digital image correlation (S-DIC) approach for quantification of posterior scleral pressure induced deformation that improves z (in-depth) resolution of the DIC measurement without losing in-plane sensitivity, while also being able to contour and map deformations of the complex-shaped ONH. Our approach combines two orthogonal axes of parallax with standard 3D DIC methods using a single high-resolution camera. The enhanced capabilities of S-DIC with respect to standard 3D DIC has been demonstrated by carrying out a complete benchmark for shape, deformation, and strain measurement on an object of known complex geometry. Our S-DIC method provided a reconstruction accuracy of 0.17% and an uncertainty in z-position measurement of 8 µm. The developed methodology has also been applied to a human posterior scleral shell, including the full peripapillary sclera and optic nerve. The relatively inexpensive S-DIC approach may provide new information on the biomechanical deformations of the optic nerve head and, thus, the death of retinal ganglion cells in primary open angle glaucoma.

Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer's clinical trial participants.

BACKGROUND: Secondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial. METHODS: Data from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status. RESULTS: Increased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status. CONCLUSION: These results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.

In situ electrokinetic enhancement for self-assembled-monolayer-based electrochemical biosensing.

This study reports a multifunctional electrode approach which directly implements electrokinetic enhancement on a self-assembled-monolayer-based electrochemical sensor for point-of-care diagnostics. Using urinary tract infections as a model system, we demonstrate that electrokinetic enhancement, which involves in situ stirring and heating, can enhance the sensitivity of the strain specific 16S rRNA hybridization assay for 1 order of magnitude and accelerate the time-limiting incubation step with a 6-fold reduction in the incubation time. Since the same electrode platform is used for both electrochemical signal enhancement and electrochemical sensing, the multifunctional electrode approach provides a highly effective strategy toward fully integrated lab-on-a-chip systems for various biomedical applications.

Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation.

Purpose: The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods: Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results: The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions: Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis.