Rasagiline Effects on Glucose Metabolism, Cognition, and Tau in Alzheimer’s Dementia

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer\u27s disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model. Results: Fifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal (P \u3c 0.025), anterior cingulate (P \u3c 0.041), and striatal (P \u3c 0.023) regions. Clinical measures showed benefit in quality of life (P \u3c 0.04). Digit Span, verbal fluency, and Neuropsychiatric Inventory (NPI) showed non-significant directional favoring of rasagiline; no effects were observed in Alzheimer\u27s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or activities of daily living. Rasagiline was generally well tolerated with low rates of adverse events and notably fewer neuropsychiatric symptoms in the active treatment group. Discussion: These outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in patients with mild to moderate AD. Rasagiline appears to affect neuronal activity in frontostriatal pathways, with associated clinical benefit potential warranting a more fully powered trial. This study illustrated the potential benefit of therapeutic repurposing and an experimental medicine proof-of-concept design with biomarkers to characterize patient and detect treatment response

5HT6 Antagonists in the Treatment of Alzheimer\u27s Dementia: Current Progress

Alzheimer\u27s disease is an important condition with a considerable and unmet disease burden in large need of continued research and more treatment options. The 5HT6 antagonists are a new class of medications to be offered. Because they are pro-cholinergic, these medications are to be used as adjuncts to acetylcholinesterase inhibitors (such as donepezil), further increasing acetylcholine in the central nervous system (CNS). Early trials of the 5HT6 antagonists showed improvements in cognition and activities of daily living when used as adjuncts to current therapies for Alzheimer\u27s dementia. However, recent phase III trials have failed to show a statistically significant improvement in cognitive function. This article will provide a comprehensive review of 5HT6 antagonists in drug development, including some that have been recently discontinued. We will discuss both the successes and failures of this drug class and provide rationale for their continued research and development

5HT6 Antagonists in the Treatment of Alzheimer’s Dementia: Current Progress

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40120-018-0095-y">https://link.springer.com/article/10.1007/s40120-018-0095-y</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

How Groundwater Level Fluctuations and Geotechnical Properties Lead to Asymmetric Subsidence: A PSInSAR Analysis of Land Deformation over a Transit Corridor in the Los Angeles Metropolitan Area

Los Angeles has experienced ground deformations during the past decades. These ground displacements can be destructive for infrastructure and can reduce the land capacity for groundwater storage. Therefore, this paper seeks to evaluate the existing ground displacement patterns along a new metro tunnel in Los Angeles, known as the Sepulveda Transit Corridor. The goal is to find the most crucial areas suffering from subsidence or uplift and to enhance the previous reports in this metropolitan area. For this purpose, we applied a Persistent Scatterer Interferometric Synthetic Aperture Radar using 29 Sentinel-1A acquisitions from June 2017 to May 2018 to estimate the deformation rate. The assessment procedure demonstrated a high rate of subsidence in the Inglewood field that is near the study area of the Sepulveda Transit Corridor with a maximum deformation rate of 30 mm/yr. Finally, data derived from in situ instruments as groundwater level variations, GPS observations, and soil properties were collected and analyzed to interpret the results. Investigation of geotechnical boreholes indicates layers of fine-grained soils in some parts of the area and this observation confirms the necessity of more detailed geotechnical investigations for future constructions in the region. Results of investigating line-of-sight displacement rates showed asymmetric subsidence along the corridor and hence we proposed a new framework to evaluate the asymmetric subsidence index that can help the designers and decision makers of the project to consider solutions to control the current subsidence

Amygdala sign, a FDG-PET signature of dementia with Lewy Bodies

BackgroundBiomarkers are being used increasingly to support the diagnosis of dementia with Lewy bodies (DLB). Novel biomarkers that increase diagnostic specificity of DLB are needed. We assessed previously known FDG-PET occipital cortex hypometabolism, and cingulate island sign biomarkers of DLB against a novel amygdala signature.MethodsRetrospective analysis of 49 patients evaluated at one tertiary memory clinic. All had a FDG-PET brain scan performed as part of their diagnostic work up evaluating three common neurodegenerative etiologies: Alzheimer dementia (AD), Frontotemporal dementia (FTD) and DLB. A consensus diagnosis of dementia was made based on accepted clinical criteria for AD, FTD and DLB. FDG-PET regional metabolism was delineated by automatic segmentation as well as manual tracing of amygdala and posterior cingulate volumes of interest. Mean normalized values calculated for regional FDG-PET signatures of DLB: occipital cortex hypometabolism and preservation of posterior cingulate and amygdala metabolism relative to whole brain metabolism were evaluated.ResultsSignificant overlap between DLB and AD patients (occipital, parietal, temporal and frontal hypometabolism) and between DLB and FTD (frontal hypometabolism and the posterior cingulate sign) were identified. Right amygdala (p = 0.028) and right posterior cingulate (p = 0.035) mean normalized regional metabolism levels were preserved in DLB compared to AD. Among subjects at less advanced stages of dementia (MoCA&gt;10), relative preservation of regional metabolism was notable across both left (p = 0.006) and right (p = 0.020) amygdala.ConclusionRelative preservation of amygdala metabolism could complement previously described FDG-PET findings in earlier stages of DLB

A Comparative Study of the AHP and TOPSIS Techniques for Dam Site Selection Using GIS: A Case Study of Sistan and Baluchestan Province, Iran

The application of multiple criteria decision-making (MCDM) techniques in real-life problems has increased in recent years. The need to build advanced decision models with higher capabilities that can support decision-making in a broad spectrum of applications, promotes the integration of MCDM techniques with applicable systems, including artificial intelligence, and Geographic Information Systems (GIS). The Analytic Hierarchy Process (AHP) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) are among the most widely adopted MCDM techniques capable of resolving water resources challenges. A critical problem associated with water resource management is dam site selection. This paper presents a comparative analysis of TOPSIS and AHP in the context of decision-making using GIS for dam site selection. The comparison was made based on geographic and water quality criteria. The geographical criteria are geology, land use, sediment, erosion, slope, groundwater, and discharge. The water quality criteria include Soluble Sodium Percentage, Total Dissolved Solid, Potential of Hydrogen, and Electrical Conductivity of water. A ratio estimation procedure was used to determine the weights of these criteria. Both methods were applied for selection of optimal sites for dams in the Sistan and Baluchestan province, Iran. The results show that the TOPSIS method is better suited to the problem of dam site selection for this study area. Actual locations of dams constructed in the area were used to verify the results of both methods.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Dietary carbohydrate quality index (CQI), cardio-metabolic risk factors and insulin resistance among adults with obesity

Abstract Background Metabolic syndrome (MetS), as a cluster of cardiometabolic risk factors, is a global public health concern due to its increasing prevalence. Considering the previous evidence of the association between carbohydrate quality and cardiometabolic risk factors, our study was aimed to evaluate any possible association between carbohydrate quality index (CQI) and cardiometabolic risk factors among obese adults. Methods In this cross-sectional study, 336 apparently healthy individuals with obesity were participated. Dietary intake was assessed by a semi-quantitative Food Frequency Questionnaire (FFQ), including 168 food items validated for the Iranian population. CQI was calculated with three components of solid carbohydrates to total carbohydrates ratio, dietary fiber intake, and dietary glycemic index (GI). Body composition was determined by bioelectrical impedance analysis (BIA). Blood pressure was measured by sphygmomanometer and enzymatic methods were used to evaluate serum lipid, glucose, and insulin concentrations. Results Subjects in the third quartile of CQI had significantly lower systolic blood pressure (SBP) (P = 0.03) and diastolic blood pressure (DBP) (P = 0.01). Participants in the higher quartiles of CQI had more intake of energy, carbohydrates, fat, saturated fatty acid (SFA), and mono-saturated fatty acid (MUFA) (P < 0.05). Moreover, the homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the second quartile of CQI [odds ratio (OR) = 0.146, P = 0.01) after adjustment for age, body mass index (BMI), sex, physical activity, socioeconomic status (SES) and energy intake. Conclusion According to our findings, a higher quality of dietary carbohydrates, determined by CQI, could be associated with a lower risk of hypertension