Melvinsvensson3970

Background Biomarker accuracy for Alzheimer disease (AD) is uncertain. Purpose To summarize evidence on biomarker accuracy for classifying AD in older adults with dementia. Data Sources Electronic bibliographic databases (searched from January 2012 to November 2019 for brain imaging and cerebrospinal fluid [CSF] tests and from inception to November 2019 for blood tests), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. Study Selection English-language studies evaluating the accuracy of brain imaging, CSF testing, or blood tests for distinguishing neuropathologically defined AD from non-AD among older adults with dementia. Studies with low or medium risk of bias were analyzed. Data Extraction Two reviewers rated risk of bias. One extracted data; the other verified accuracy. Data Synthesis Fifteen brain imaging studies and 9 CSF studies met analysis criteria. Median sensitivity and specificity, respectively, were 0.91 and 0.92 for amyloid positron emission tomography (PET), 0.89 and ally heterogeneous studies of uncertain applicability to typical clinical settings, amyloid PET, 18F-FDG PET, and MRI were highly sensitive for neuropathologic AD. Amyloid PET, 18F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation. Primary Funding Source Agency for Healthcare Research and Quality. (PROSPERO CRD42018117897).Background Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. Purpose To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. Data Sources Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. Study Selection English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). Data Extraction Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. Data Synthesis Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared wiort-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. Primary Funding Source Agency for Healthcare Research and Quality. (PROSPERO CRD42018117897).Purpose To test the hypothesis that hyperglycemia perturbs neurovascular\ coupling and compromises retinal vascular response during transition from dark to light in healthy subjects using optical coherence tomography angiography (OCTA). Methods Ten eyes of 10 healthy subjects were tested, first during fasting and then after receiving a 75-g oral glucose solution. In both sessions, OCTA imaging was done in the dark-adapted state and at 50 seconds, 2 minutes, 5 minutes, and 15 minutes of ambient light. Parafoveal vessel density (VD) and adjusted flow index (AFI) were calculated for the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP), and vessel length density was calculated for the SCP. MI-773 molecular weight These measurements were compared among conditions after adjusting for age, refractive error, and OCTA scan quality. Results Hyperglycemia leads to a complete reversal of dark/light adaptation trends in VD and AFI in all layers of the inner retina. In the dark, there is significantly decreased VD in the DCP in hyperglycemia. With a transition to light in hyperglycemia, we observed decreased VD in the SCP, increased vessel density in the MCP and DCP, and decreased AFI in all three layers. Conclusions Our results show that hyperglycemia significantly disrupts neurovascular coupling in healthy eyes, with potential metabolic deficits affecting photoreceptor oxygen demands during dark adaptation and the inner retina during light exposure. In pathological states, such as diabetic retinopathy, where the vasculature is already attenuated, retinal neurons may be exquisitely vulnerable to intermittent hyperglycemic challenge, which should be the focus of future studies.Purpose To determine whether high glucose (HG) compromises internalization of lysyl oxidase (LOX) through excess binding of LOX with extracellular matrix (ECM) proteins. Methods To determine whether HG promotes binding of LOX with ECM proteins, fibronectin (FN) and collagen IV (Coll IV), total or ECM-only proteins from rat retinal endothelial cells grown in normal (N; 5 mM) or HG (30 mM) medium were analyzed by coimmunoprecipitation and Western blot (WB). In parallel, coimmunostaining was performed to determine changes in LOX binding to FN or Coll IV. To determine the effect of HG on extracellular LOX levels, medium in which cells were grown for 1, 3, 5, and 7 days were assessed for LOX levels. Results WB analysis using total protein showed LOX overexpression and elevated levels of LOX bound to Coll IV or FN in HG condition. Similarly, a significant increase in LOX bound to FN or Coll IV was observed in ECM-only protein. These data were supported by Z-stack confocal microscopy images from coimmunostaining. Furthermore, immunostaining performed on ECM layer revealed increased presence of LOX bound to Coll IV or FN. Additionally, when media from cells grown in HG was monitored, a maximal increase in LOX level was observed by day 3, which declined by day 7. Conclusions Findings indicate that HG promotes binding of LOX to FN and Coll IV extracellularly that results in reduced LOX internalization, attenuation of negative feedback, and upregulation of LOX expression associated with diabetic retinopathy.Purpose The purpose of this study was to use three-dimensional confocal microscopy to quantify the spatial patterns of capillary network alterations in nonproliferative diabetic retinopathy (NPDR). Methods The retinal microvasculature was perfusion-labelled in seven normal human donor eyes and six age-matched donor eyes with NPDR. The peripapillary microcirculation was studied using confocal scanning laser microscopy. Capillary density and diameters of the radial peripapillary capillary plexus (RPCP), superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were quantified and compared. Three-dimensional visualization strategies were also used to compare the communications between capillary beds and precapillary arterioles and postcapillary venules. Results Mean capillary diameter was significantly increased in the NPDR group (P less then 0.001). Intercapillary distance was significantly increased in the DCP (P = 0.004) and RPCP (P = 0.022) of the NPDR group (P = 0.