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Alzheimers and diabetes

Jesse Mez, Jaeyoon Chung, Gyungah Jun, Joshua Kriegel, Alexandra P Bourlas, Richard Sherva, Mark W Logue, Lisa L Barnes, David A Bennett, Joseph D Buxbaum, Goldie S Byrd, Paul K Crane, Nilüfer Ertekin-Taner, Denis Evans, M Daniele Fallin, Tatiana Foroud, Alison Goate, Neill R Graff-Radford, Kathleen S Hall, M Ilyas Kamboh, Walter A Kukull, Eric B Larson, Jennifer J Manly, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard D Schellenberg, Kathryn L Lunetta, Lindsay A Farrer
INTRODUCTION: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power. METHODS: We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information...
October 19, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
K Rygiel
Alzheimer's disease (AD) is a neurodegenerative disease, in which an accumulation of toxic amyloid beta in the brain precedes the emergence of clinical symptoms. AD spectrum consists of presymptomatic, early symptomatic, and symptomatic phase of dementia. At present, no pharmacotherapy exists to modify or reverse a course of AD, and only symptomatic treatments are available. Many elderly patients, diagnosed with multiple medical conditions (such as cardiovascular diseases, Type 2 diabetes mellitus, and cerebrovascular diseases) are at increased risk of the development of mild cognitive impairment (MCI), AD, and vascular dementia...
October 2016: Journal of Postgraduate Medicine
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Jeremy J Pruzin, Julie A Schneider, Ana W Capuano, Sue E Leurgans, Lisa L Barnes, Rexford S Ahima, Steven E Arnold, David A Bennett, Zoe Arvanitakis
We examined the relationship of diabetes and hemoglobin A1C (A1C) to 2 common causes of dementia. The study included 1228 subjects who underwent annual clinical evaluations and a brain autopsy at death, as part of a Rush longitudinal cohort study of aging. A total of 433 subjects had A1C data available. Neuropathologic evaluations documented the size and location of infarcts. Modified silver stain-based Alzheimer disease (AD) measures included global and regional scores. We used regression analyses to examine associations of diabetes and A1C with overall and regional neuropathology...
October 17, 2016: Alzheimer Disease and Associated Disorders
Seong-Tshool Hong
The human intestine contains a massive and complex microbial community called gut microbiota. A typical human carries 100 trillion microbes in his/her body which is 10 times greater than the number of their host cells, i.e. whole number of human cells. A combined microbial genome constituting gut microbiota is well excess our own human genome. The microbial composition of gut microbiotata and its role on diseases became a booming area of research, presenting a new paradigm of opportunities for modern medicines...
September 2016: Journal of Hypertension
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Suzanne Oparil
Heart disease, stroke, and kidney failure are leading causes of death worldwide, and hypertension is a significant risk factor for each. Hypertension is less common in women, compared to men, in those younger than 45 years of age. This trend is reversed in those 65 years and older. In the US between 2011-2014, the prevalence of hypertension in women and men by age group was 6% vs 8% (18-39 years), 30% vs 35% (40-59 years), and 67% vs 63% (60 years and over). Awareness, treatment, and control rates differ between genders with women being more aware of their diagnosis (85% vs 80%), more likely to take their medications (81% vs 71%) and more frequently having controlled hypertension (55% vs 49%)...
September 2016: Journal of Hypertension
Huiting Su, Ning Na, Xiaodong Zhang, Yong Zhao
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins...
October 17, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Farha Naz, Neha Sami, Abu Turab Naqvi, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Human microtubule affinity-regulating kinase 4 (MARK4) is considered as an encouraging drug target for the design and development of inhibitors to cure several life threatening diseases such as Alzheimer disease, cancer, obesity and type-II diabetes. Recently, we have reported four ligands namely, BX-912, BX-795, PKR-inhibitor and OTSSP167 (hydrochloride) which bind preferentially to the two different constructs of human MARK4 containing kinase domain. To ensure the role of ubiquitin associated (UBA) domain in the ligand binding, we made a newer construct of MARK4 which contain both kinase and UBA domains, named as MARK4-F3...
October 16, 2016: Journal of Biomolecular Structure & Dynamics
Nan Zhang, Shengchang Yang, Chang Wang, Jianghua Zhang, Lifang Huo, Yiru Cheng, Chuan Wang, Zhanfeng Jia, Leiming Ren, Lin Kang, Wei Zhang
Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively. Multiple studies have indicated a strong correlation between these two diseases. Amylin oligomerization in the brain appears to be a novel risk factor for developing AD. Although amylin aggregation has been demonstrated to induce cytotoxicity in neurons through altering Ca(2+) homeostasis, the underlying mechanisms have not been fully explored...
October 12, 2016: Neuropharmacology
E M Ribe, S Lovestone
As populations across the world both age and become more obese, the numbers of individuals with Alzheimer's disease and diabetes are increasing; posing enormous challenges for society and consequently becoming priorities for governments and global organizations. These issues, an ageing population at risk of neurodegenerative diseases such as Alzheimer's disease and an increasingly obese population at risk of metabolic alterations such as type 2 diabetes, are usually considered as independent conditions, but increasing evidence from both epidemiological and molecular studies link these disorders...
October 14, 2016: Journal of Internal Medicine
(no author information available yet)
BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010...
October 8, 2016: Lancet
E Candeias, A I Duarte, I Sebastião, M A Fernandes, A I Plácido, C Carvalho, S Correia, R X Santos, R Seiça, M S Santos, C R Oliveira, P I Moreira
Type 2 diabetes (T2D) is a highly concerning public health problem of the twenty-first century. Currently, it is estimated that T2D affects 422 million people worldwide with a rapidly increasing prevalence. During the past two decades, T2D has been widely shown to have a major impact in the brain. This, together with the cognitive decline and increased risk for dementia upon T2D, may arise from the complex interaction between normal brain aging and central insulin signaling dysfunction. Among the several features shared between T2D and some neurodegenerative disorders (e...
October 11, 2016: Molecular Neurobiology
Wei Li, Tao Wang, Shifu Xiao
BACKGROUND: Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer's disease (AD), so identification of the related risk factors can be helpful. Although the association between type 2 diabetes mellitus (T2DM) and these modest changes in cognition is well established, whether T2DM will promote the transformation of MCI into AD is not a unified conclusion. OBJECTIVE: This study aims to explore the relationship between T2DM and MCI in the elderly population living in the community in Shanghai, People's Republic of China...
2016: Neuropsychiatric Disease and Treatment
Martín Carballo-Pacheco, Birgit Strodel
Intrinsically disordered proteins are essential for biological processes such as cell signalling, but are also associated to devastating diseases including Alzheimers disease, Parkinsons disease or type II diabetes. Because of their lack of a stable threedimensional structure, molecular dynamics simulations are often used to obtain atomistic details that cannot be observed experimentally. The applicability of molecular dynamics simulations depends on the accuracy of the force field chosen to represent the underlying free energy surface of the system...
October 11, 2016: Protein Science: a Publication of the Protein Society
Frank J Wolters, Francesco U S Mattace-Raso, Peter J Koudstaal, Albert Hofman, M Arfan Ikram
BACKGROUND: Orthostatic hypotension (OH) is a common cause of transient cerebral hypoperfusion in the population. Cerebral hypoperfusion is widely implicated in cognitive impairment, but whether OH contributes to cognitive decline and dementia is uncertain. We aimed to determine the association between OH and the risk of developing dementia in the general population. METHODS AND FINDINGS: Between 4 October 1989 and 17 June 1993, we assessed OH in non-demented, stroke-free participants of the population-based Rotterdam Study...
October 2016: PLoS Medicine
Sara Mostafalou, Mohammad Abdollahi
Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity...
October 8, 2016: Archives of Toxicology
Jayasankar Kosaraju, R M Damian Holsinger, Lixia Guo, Kin Yip Tam
Glucagon-like peptide-1 (GLP-1) is an incretin hormone shown to be active in the treatment of type-2 diabetes (T2D) and has also been shown as efficacious in Alzheimer's disease (AD). Dipeptidyl peptidase-4 (DPP-4), an enzyme that is expressed in numerous cells, rapidly inactivates endogenous GLP-1. Therefore, DPP-4 inhibition is employed as a therapeutic avenue to increase GLP-1 levels in the management of T2D. The effectiveness of DPP-4 inhibitors in the treatment of AD has been reported in various animal models of AD...
October 3, 2016: Molecular Neurobiology
Sibhghatulla Shaikh, Syed Mohd Danish Rizvi, Tabinda Suhail, Shazi Shakil, Adel M Abuzenadah, Rukhsar Anis, Deeba Naaz, Mohd Haneef, Adnan Ahmad, Latafat Choudhary
An increasing number of research evidences indicate linkage between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD); the two most common diseases of aging. In addition, T2DM and AD also share some common pathophysiological features. Therefore, dual therapy that targets both the diseases can be regarded as a beneficial approach. Acetylcholinesterase (AChE) and beta-secretase (BACE) have been considered as potential therapeutic targets for AD. Accordingly, the piece of work presented here describes the binding of anti-diabetic drugs (Jardiance, Suiny and Nesina) with AChE and BACE so as to further investigate connecting bridges concerning the treatment of these two diseases...
October 3, 2016: CNS & Neurological Disorders Drug Targets
Jiachun Liu, Yan-Ling Wu, Huri Piao, Xiaoyin Zhao, Wen Zhang, Yanli Wang, Minrui Liu
At present, diseases resulting from various reasons have been causing deadly fears to humans and previously incogitable losses to health. Meanwhile, the patient compliance has been weakening because of drug resistance and serious drug adverse effects. There is therefore an urgent need for the development of novel structural agents. Rhodanine derivatives have represented wide biological activities, as well as significant industrial applications, which suggests that rhodanine heterocycle represents a key structural motif in heterocyclic chemistry and occupies a prominent position in drug discovery...
September 28, 2016: Mini Reviews in Medicinal Chemistry
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