Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline.

IMPORTANCE: Adults with Down syndrome (DS) are at high-risk of revealing Alzheimer's disease (AD) pathology, in part due to the triplication of chromosome 21 encoding the amyloid precursor protein. Adults with DS are uniformly affected by AD pathology by their 30's and have a 70% to 80% chance of clinical dementia by their 60's. Our previous studies have assessed longitudinal changes in amyloid beta (Aß) accumulation in DS. OBJECTIVE: The goal of the present study was to assess the presence of brain tau using [18F]AV-1451 positron emission tomography (PET) in DS and to assess the relationship of brain tau pathology to Aß using Pittsburgh Compound B (PiB)-PET. DESIGN: Cohort study. SETTING: Multi-center study. PARTICIPANTS: Participants consisted of a sample of individuals with DS and sibling controls recruited from the community; exclusion criteria included contraindications for magnetic resonance imaging (MRI) and/or a medical or psychiatric condition that impaired cognitive functioning. EXPOSURES: PET brain scans to assess Aß ([11C]PiB) and tau ([18F]AV-1451) burden. MAIN OUTCOMES AND MEASURES: Multiple linear regression models (adjusted for chronological age, sex and performance site) were used to examine associations between regional [18F]AV-1451 standard uptake value ratio (SUVR) (based on regions associated with Braak stages 1-6) and global [11C]PiB SUVR (as both a continuous and dichotomous variable). RESULTS: A cohort of 156 participants (mean age = 39.05, SD(8.4)) were examined. These results revealed a significant relationship between in vivo Aß and tau pathology in DS. As a dichotomous variable, [18F]AV-1451 retention was higher in each Braak region in PiB(+) participants. We also found, based on our statistical models, starting with the Braak 3 region of interest (ROI), an acceleration of [18F]AV-1451 SUVR deposition with [11C]PiB SUVR increases.

An improved algorithm of white matter hyperintensity detection in elderly adults.

Automated segmentation of the aging brain raises significant challenges because of the prevalence, extent, and heterogeneity of white matter hyperintensities. White matter hyperintensities can be frequently identified in magnetic resonance imaging (MRI) scans of older individuals and among those who have Alzheimer's disease. We propose OASIS-AD, a method for automatic segmentation of white matter hyperintensities in older adults using structural brain MRIs. OASIS-AD is an approach evolved from OASIS, which was developed for automatic lesion segmentation in multiple sclerosis. OASIS-AD is a major refinement of OASIS that takes into account the specific challenges raised by white matter hyperintensities in Alzheimer's disease. In particular, OASIS-AD combines three processing steps: 1) using an eroding procedure on the skull stripped mask; 2) adding a nearest neighbor feature construction approach; and 3) applying a Gaussian filter to refine segmentation results, creating a novel process for WMH detection in aging population. We show that OASIS-AD performs better than existing automatic white matter hyperintensity segmentation approaches.

When worry may be good for you: Worry severity and limbic-prefrontal functional connectivity in late-life generalized anxiety disorder.

BACKGROUND: Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. METHODS: We recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. RESULTS: Amygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. LIMITATIONS: Our limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. CONCLUSIONS: This suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry.

Involvement of Oxidative Stress in COPD.

Chronic obstructive pulmonary disease (COPD) is a disease that affects the lungs and is defined by a variety of symptoms that combined with co-morbidities lead to a decline of the patients quality of life. The principal etiology of chronic obstructive pulmonary disease is smoking and air pollution that lead to oxidative and carbonyl stress. This review based on a search of PubMed, OxLIP+/SOLO (Bodleian Libraries) database (from 1991 to 2017) of relevant articles based on assessment of oxidative stress pathways involvement in COPD. Intracellular reactions that take place in organisms and aerobic cells have as by-products reactive oxygen species (ROS) and free radicals. Oxidative stress involved in pathogenesis of COPD is the result of lowered antioxidative potential combined with increased burden of oxidants. Molecular mechanisms underlying COPD pathways are not yet well understood, despite intensive research all over the world. A change in balance between Oxidants and antioxidants in the lungs as well as within the circulatory system, gene polymorphisms, and activation of transcription factors contribute to the molecular pathogenesis of COPD. Future research is needed in order to identify which patients will develop in time a susceptibility to damage caused by ROS and to determine if controlling ROS will have an effect on the progression of COPD.

In the grip of worry: cerebral blood flow changes during worry induction and reappraisal in late-life generalized anxiety disorder.

This corrects the article DOI: 10.1038/tp.2017.180.

Association between change in brain gray matter volume, cognition, and depression severity: Pre- and post- antidepressant pharmacotherapy for late-life depression.

Late-life depression (LLD) is associated with cognitive impairments and reduced gray matter volume (GMV); however the mechanisms underlying this association are not well understood. The goal of this study was to characterize changes in depression severity, cognitive function, and brain structure associated with pharmacologic antidepressant treatment for LLD. We administered a detailed neurocognitive battery and conducted structural magnetic resonance imaging (MRI) on 26 individuals with LLD, pre-/post-a 12-week treatment trial with venlafaxine. After calculating changes in cognitive performance, GMV, and depression severity, we calculated Pearson's correlations, performed permutation testing, and false discovery rate correction. We found that loss of GMV over 12 weeks in the superior orbital frontal gyrus was associated with less improvement in depression severity and that increased GMV in the same was associated with greater improvement in depression severity. We detected no associations between changes in cognitive performance and improvements in either depressive symptoms or changes in GMV.

In the grip of worry: cerebral blood flow changes during worry induction and reappraisal in late-life generalized anxiety disorder.

Severe worry includes a complex blend of maladaptive affective and cognitive processes. Contrary to other forms of anxiety, there is no consensus in the field regarding the neural basis of worry. To date, no study has looked at neural patterns associated specifically with in-scanner induction and reappraisal of worry. In this study, we attempt to describe distinct components of the 'neural phenomenology' of worry: induction, maintenance, severity and reappraisal, by using a personalized, in-scanner worry script. Twenty older, non-anxious participants and twenty late-life generalized anxiety disorder (GAD) participants were included. Whole-brain axial pseudo-continuous arterial spin-labeling scans were collected. We used a voxel-wise two-way ANOVA to test the group-by-block interaction. Worry induction was associated with greater cerebral blood flow (CBF) in the visual cortex, thalamus, caudate and medial frontal cortex compared with the rest. Reappraisal was associated with greater CBF in similar regions, whereas the orbital frontal gyrus showed lower CBF relative to rest. Relative to non-anxious participants, GAD had greater CBF in multiple regions during worry induction (visual and parietal cortex, middle and superior frontal) and lower CBF during reappraisal in the supplemental motor area, middle cingulate gyrus, insula and putamen. Except for the thalamus, there was no change in CBF throughout the five blocks of worry induction and reappraisal. Severe worry is distinctly associated with increased CBF in several neocortical regulatory regions. We present new data supporting the view of worry as a complex process, engaging multiple regions in the initiation, maintenance and reappraisal of worry.

Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters.

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.

NOD2 Arg702Trp Polymorphism in Romanian Patients with Gastric Cancer.

PURPOSE: Our study aimed to assess a possible correlation between NOD2 Arg702Trp (rs2066844) polymorphism and gastric cancer risk in a Romanian population. MATERIAL/METHODS: A total of 322 subjects (72 patients with gastric adenocarcinoma and 250 healthy controls) were included. Genomic DNA was extracted from blood leukocytes and NOD2 Arg702Trp polymorphism was genotyped by Real-Time PCR using specific TaqMan probes. RESULTS: No statistically significant difference was observed between gastric cancer patients and controls when we compared one genotype with other genotype (the CC genotype serves as reference) (OR 0.45, 95% CI: 0.10 - 2.05) or when we compared allele frequencies (the C allele serves as reference) (OR 0.46, 95% CI: 0.11 - 2.04). We examined separately the association of this polymorphism with tumor site and histologic type and no correlation was found. CONCLUSION: NOD2 Arg702Trp polymorphism is not associated with gastric cancer risk and further investigations are needed to elucidate the contribution of NOD2 gene in gastric carcinogenesis.

Iron Oxide Nanoparticles Biodistribution in an Experimental Pig Model - A New Approach for Delivery and Imaging.

Iron oxide nanoparticles (IONs) are of great interest in medicine, with great potential for imaging diagnostics, as well as therapeutic. Biomedical applications of IONs have been suggested for magnetic resonance imaging (MRI), with two available contrast agents on the market. However, new developments in biocompatibility and biodistribution are necessary as many new physiochemical features of coatings have been proposed for a good safety profile. MATERIALS AND METHODS: Our study objective was to assess a different setting in terms of biodistribution of IONs coated with citric acid on an experimental pig model, based on EUS-guided portal vein (PV) injection. Four pigs were subjected to EUS procedures and portal vein injection of an IONs solution. All animals were kept under surveillance for the next 24 hours and euthanized. Necropsy was performed and their organs were harvested, visualized with a 3T MRI scanner and sent to pathological examination. RESULTS: All pigs had no change in their behavior and no signs of complications were encountered. There were no problems in identifying the pig's PV under EUS-guidance. The IONs solution was clearly visualized on ultrasound live imaging, during EUS-injection. MRI and histopathological data confirmed all the deposits using Prussian Blue staining. CONCLUSIONS: This paper comes forward as a first phase of assessing new future therapeutic options and their distribution within the main organs depending on their characteristics. In our opinion this new distribution option has a strong incentive to the research of therapeutic and imaging areas and is worthy of further appraisal.

Motion correction of PET brain images through deconvolution: I. Theoretical development and analysis in software simulations.

Image quality is significantly degraded even by small amounts of patient motion in very high-resolution PET scanners. Existing correction methods that use known patient motion obtained from tracking devices either require multi-frame acquisitions, detailed knowledge of the scanner, or specialized reconstruction algorithms. A deconvolution algorithm has been developed that alleviates these drawbacks by using the reconstructed image to estimate the original non-blurred image using maximum likelihood estimation maximization (MLEM) techniques. A high-resolution digital phantom was created by shape-based interpolation of the digital Hoffman brain phantom. Three different sets of 20 movements were applied to the phantom. For each frame of the motion, sinograms with attenuation and three levels of noise were simulated and then reconstructed using filtered backprojection. The average of the 20 frames was considered the motion blurred image, which was restored with the deconvolution algorithm. After correction, contrast increased from a mean of 2.0, 1.8 and 1.4 in the motion blurred images, for the three increasing amounts of movement, to a mean of 2.5, 2.4 and 2.2. Mean error was reduced by an average of 55% with motion correction. In conclusion, deconvolution can be used for correction of motion blur when subject motion is known.

Low-dose nonenhanced head CT protocol for follow-up evaluation of children with ventriculoperitoneal shunt: reduction of radiation and effect on image quality.

BACKGROUND AND PURPOSE: Children with a shunt for hydrocephalus often undergo multiple follow-up head CT scans, increasing the risk for long-term effects of ionizing radiation. The purpose of our study was to evaluate if an unenhanced low-dose head CT could consistently provide acceptable image quality and diagnostic information. MATERIALS AND METHODS: Ninety-two children (mean age, 9 years; range, 8 months to 21 years; 45 boys and 47 girls) with a shunt for hydrocephalus and no clinical evidence of shunt malfunction who were referred for a follow-up nonenhanced head CT were included in the study. All studies were performed on a 4-section multidetector CT. Two CT studies were selected retrospectively for each patient, 1 performed at standard dose (220 mA) and 1 at low dose (80 mAs). Two radiologists independently evaluated and graded both standard-dose and low-dose studies for various image quality parameters. Attenuation and noise levels were measured, and gray-white differentiation and contrast-to-noise ratio (CNR) were calculated. RESULTS: Low-dose CT resulted in 63% mean dose reduction. All low-dose CT scans were diagnostically acceptable. Image quality parameters were significantly lower at low dose (P = .0001) except for the parameters for streak artifacts (P = .46) and need for further imaging (P = .47), which were higher. Mean noise levels were significantly higher (P = .001) in low-dose studies, whereas CNR was significantly higher in standard dose CT (P = .001). A moderate to perfect agreement was noted between the 2 readers with regard to image quality assessment (65%-99%). CONCLUSION: Low-dose nonenhanced head CT consistently provides diagnostically acceptable images with relevant diagnostic information in children with VP shunts resulting in substantial dose savings.