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Journal of Alzheimer's Disease: JAD

Ivan Koychev, Brook Galna, Henrik Zetterberg, Jennifer Lawson, Giovanna Zamboni, Basil H Ridha, James B Rowe, Alan Thomas, Robert Howard, Paresh Malhotra, Craig Ritchie, Simon Lovestone, Lynn Rochester
Gait disturbances are some of the earliest changes in dementia and their monitoring presents an opportunity for early diagnosis. The exact relationship between gait and well-established biomarkers of Alzheimer's disease (AD) remains to be clarified. In this study we compared gait-related measures with cerebrospinal fluid (CSF) markers of AD pathology. We recruited seventeen participants with mild AD in a multi-site study and performed gait assessment as well as lumbar punctures to obtain CSF. CSF Aβ42/Aβ40 and Aβ42/Aβ38 correlated positively with measures of variability (step time and step length) in the clinic-based assessments...
September 4, 2018: Journal of Alzheimer's Disease: JAD
Sid E O'Bryant, Fan Zhang, Leigh A Johnson, James Hall, Melissa Edwards, Paula Grammas, Esther Oh, Constantine G Lyketsos, Robert A Rissman
BACKGROUND: To date, the therapeutic paradigm for Alzheimer's disease (AD) focuses on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy. OBJECTIVE: To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy. METHODS: Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice-daily) or placebo...
September 4, 2018: Journal of Alzheimer's Disease: JAD
Deepika Shukla, Pravat K Mandal, Lars Ersland, Eli Renate Grüner, Manjari Tripathi, Partha Raghunathan, Ankita Sharma, G R Chaithya, Khushboo Punjabi, Christopher Splaine
Molecular dynamics simulation and in vitro nuclear magnetic resonance (NMR) studies on glutathione (GSH) indicated existence of conformations (closed and extended). The present work in a multi-center research setting investigates in-depth, analysis of GSH conformers in vivo using a common magnetic resonance spectroscopy (MRS) protocol and signal processing scheme. MEGA-PRESS pulse sequence was applied on healthy subjects using 3T Philips MRI scanner (India) and 3T GE MRI scanner (Norway) using the same experimental parameters (echo time, repetition time, and selective 180° refocusing ON-pulse at 4...
September 1, 2018: Journal of Alzheimer's Disease: JAD
Tao Huan, Tran Tran, Jiamin Zheng, Shraddha Sapkota, Stuart W MacDonald, Richard Camicioli, Roger A Dixon, Liang Li
Using a non-invasive biofluid (saliva), we apply a powerful metabolomics workflow for unbiased biomarker discovery in Alzheimer's disease (AD). We profile and differentiate Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and AD groups. The workflow involves differential chemical isotope labeling liquid chromatography mass spectrometry using dansylation derivatization for in-depth profiling of the amine/phenol submetabolome. The total sample (N = 109) was divided in to the Discovery Phase (DP) (n = 82; 35 CN, 25 MCI, 22 AD) and a provisional Validation Phase (VP) (n = 27; 10 CN, 10 MCI, 7 AD)...
August 28, 2018: Journal of Alzheimer's Disease: JAD
Konstantin Bloch, Irit Gil-Ad, Alexey Vanichkin, Shay Henry Hornfeld, Michal Taler, Shira Dar, Dmitry Azarov, Pnina Vardi, Abraham Weizman
BACKGROUND: Alzheimer's disease (AD) is often associated with brain insulin resistance and peripheral metabolic dysfunctions. Recently, we developed a model of sporadic AD associated with obesity-related peripheral metabolic abnormalities in Lewis rats using intracerebroventricular administration of streptozotocin (icv-STZ). OBJECTIVE: We aimed to assess the effect of intracranially grafted pancreatic islets on cognitive and peripheral metabolic dysfunctions in the icv-STZ Lewis rats...
August 28, 2018: Journal of Alzheimer's Disease: JAD
Shanshan Wang, Benhong He, Weijian Hang, NingHua Wu, Liangtao Xia, Xu Wang, Qianying Zhang, Xinwen Zhou, Zuohua Feng, Qingjie Chen, Juan Chen
BACKGROUND: Axonopathy is closely linked to the development of diabetic encephalopathy induced by type II diabetes (T2D). Berberine has been shown to cross the blood-brain barrier and holds promising effect for neuronal damage in diabetes. OBJECTIVE: The present study investigated the protective effect and the underlying mechanism of berberine on neuronal axonopathy in both in vitro and in vivo models. METHODS: High glucose/high fat diet and streptozotocin injection-induced T2D rat model was used...
August 28, 2018: Journal of Alzheimer's Disease: JAD
Sabela C Mallo, Zahinoor Ismail, Arturo X Pereiro, David Facal, Cristina Lojo-Seoane, María Campos-Magdaleno, Onésimo Juncos-Rabadán
BACKGROUND: Neuropsychiatric symptoms (NPS) are non-cognitive, behavioral, or psychiatric symptoms, common in mild cognitive impairment (MCI) and associated with a higher risk of dementia. Mild behavioral impairment (MBI) is a validated diagnostic entity, that describes the emergence of later life NPS in pre-dementia states. The Mild Behavioral Impairment Checklist (MBI-C) is the first measure developed to assess MBI. OBJECTIVE: To estimate the prevalence of MBI in people with MCI and to study the score distribution, sensitivity, specificity, diagnostic utility of the MBI-C, and its correlations with neuropsychological tests...
August 28, 2018: Journal of Alzheimer's Disease: JAD
Fernando Garzón, Débora Coimbra, Antoni Parcerisas, Yamila Rodriguez, Julio Cesar García, Eduardo Soriano, Ramón Rama
Many experimental studies show that erythropoietin (EPO) has a neuroprotective action in the brain. EPO in acute and chronic neurological disorders, particularly in stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, has neuroprotective effects. We previously reported the neuroprotective effect of NeuroEPO, a low sialic form of EPO, against oxidative stress induced by glutamate excitotoxicity. In this paper, we analyze the effect of NeuroEPO against apoptosis induced by glutamate excitotoxicity in primary neuronal cultures obtained from the forebrains of Wistar rat embryos after 17 days of gestation...
August 27, 2018: Journal of Alzheimer's Disease: JAD
Dennis M Hedderich, Judith E Spiro, Oliver Goldhardt, Johannes Kaesmacher, Benedikt Wiestler, Igor Yakushev, Claus Zimmer, Tobias Boeckh-Behrens, Timo Grimmer
BACKGROUND: Volumetric quantification of structural MRI has been shown to increase the diagnostic accuracy of patients with mild cognitive impairment (MCI); however, its implementation in clinical routine is usually technically difficult and time-consuming. OBJECTIVE: The purpose of this study was to investigate whether volumetric information obtained from the free and easy-to-use online tool volBrain can improve correct identification of MCI patients with Alzheimer's disease (AD) compared to visual reading...
August 27, 2018: Journal of Alzheimer's Disease: JAD
Leonardo Tariciotti, Matthew Casadei, Lawrence S Honig, Andrew F Teich, Guy M McKhann Ii, Giuseppe Tosto, Richard Mayeux
BACKGROUND: Elevated total tau (tTau), 181-phosphorylated phosphorylated tau (pTau), and low amyloid-β42 (Aβ42) in cerebrospinal fluid (CSF) represent a diagnostic biomarker for Alzheimer's disease (AD). OBJECTIVE: The goal was to determine the overall accuracy of CSF Aβ42, tTau, pTau, and the Aβ42/total tau index (ATI) in a non-research, clinical setting for the diagnosis of AD. METHODS: From medical records in 1,016 patients that had CSF studies for dementia over a 12-year period (2005 to 2017), we calculated the sensitivity and specificity of CSF Aβ42, tTau, and pTau and the ATI in relation to the final clinical diagnosis...
August 24, 2018: Journal of Alzheimer's Disease: JAD
Bin Wang, Liwen Miao, Yan Niu, Rui Cao, Dandan Li, Pengfei Yan, Hao Guo, Tianyi Yan, Jinglong Wu, Jie Xiang
Alzheimer's disease (AD) disrupts the topological architecture of whole-brain connectivity. Minimum spanning tree (MST), which captures the most important connections in a network, has been considered an unbiased method for brain network analysis. However, the alterations in the MST of functional brain networks during the progression of AD remain unclear. Here, we performed an MST analysis to examine the alterations in functional networks among normal controls (NCs), mild cognitive impairment (MCI) patients, and AD patients...
August 23, 2018: Journal of Alzheimer's Disease: JAD
John D Finan, Shreya V Udani, Vimal Patel, Julian E Bailes
Functional outcomes after traumatic brain injury (TBI) vary widely across patients with apparently similar injuries. This variability hinders prognosis, therapy, and clinical innovation. Recently, single nucleotide polymorphism (SNPs) that influence outcome after TBI have been identified. These discoveries create opportunities to personalize therapy and stratify clinical trials. Both of these changes would propel clinical innovation in the field. This review focuses on one of most well-characterized of these SNPs, the Val66Met SNP in the brain-derived neurotrophic factor (BDNF) gene...
August 23, 2018: Journal of Alzheimer's Disease: JAD
Oren Tene, Hen Hallevi, Amos D Korczyn, Ludmila Shopin, Jeremy Molad, Clemens Kirschbaum, Natan M Bornstein, Shani Shenhar-Tsarfaty, Efrat Kliper, Eitan Auriel, Sali Usher, Tobias Stalder, Einor Ben Assayag
BACKGROUND AND OBJECTIVE: Previous studies suggest that excessive cortisol levels after stroke are associated with cognitive dysfunction. However, limited data exist regarding associations between post-stroke cortisol levels, brain abnormalities, genetic factors, and cognitive outcome. We sought to study these issues in a longitudinal stroke survivors cohort. METHODS: Data from 182 cognitively intact ischemic stroke patients from the TABASCO study were available...
August 23, 2018: Journal of Alzheimer's Disease: JAD
Fernanda Crunfli, Caio Henrique Mazucanti, Ruan Carlos Macêdo de Moraes, Andressa Pereira Costa, Alice Cristina Rodrigues, Cristoforo Scavone, Andréa da Silva Torrão
Sporadic Alzheimer's disease (sAD) is associated with energy metabolism deficiency and impairment of insulin receptor (IR) signaling in the brain. In this context, low doses of intracerebroventricular (icv) injection of streptozotocin (STZ) in rodents has been used as an experimental model of sAD which leads to an insulin-resistant brain state and neurodegeneration. However, the STZ effects on brain insulin signaling-related proteins it is not appropriately elucidated. The aim of this study was to evaluate the beginning and progression of alterations in the brain IR pathway of rats after 1, 3, 5, and 7 days of STZ injection and investigate intracellular signaling involved on STZ induced insulin resistance...
August 23, 2018: Journal of Alzheimer's Disease: JAD
Sakae Yumoto, Shigeo Kakimi, Akira Ishikawa
Increasing evidence indicates that metal-induced oxidative stress plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Recently, the presence of 8-hydroxydeoxyguanosine, a biomarker of oxidative DNA damage, was demonstrated in nuclear DNA (nDNA) in the AD brain. Iron (Fe) is a pro-oxidant metal capable of generating hydroxyl radicals that can oxidize DNA, and aluminum (Al) has been reported to facilitate Fe-mediated oxidation. In the present study, we examined the elements contained in the nuclei of nerve cells in AD brains using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS)...
August 23, 2018: Journal of Alzheimer's Disease: JAD
Christa Dang, Karra D Harrington, Yen Ying Lim, David Ames, Jason Hassenstab, Simon M Laws, Nawaf Yassi, Martha Hickey, Stephanie Rainey-Smith, Joanne Robertson, Hamid R Sohrabi, Olivier Salvado, Michael Weinborn, Victor L Villemagne, Christopher C Rowe, Colin L Masters, Paul Maruff
BACKGROUND: Preclinical Alzheimer's disease (AD) is defined by cerebral amyloid-β positivity (Aβ+) in cognitively normal (CN) older adults. OBJECTIVE: To estimate the risk of progression to the symptomatic stages of AD due to PET Aβ+ and the extent that progression was influenced by other demographic, genetic, and clinical characteristics in a large prospective study. METHODS: Fine-Gray subdistribution modeling was used to examine the risk of progression from CN to MCI/dementia due to Aβ+, APOEɛ4 carriage, and their interaction in the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging CN cohort (n = 599) over 8 years...
August 22, 2018: Journal of Alzheimer's Disease: JAD
Vijay K Ramanan, Scott A Przybelski, Jonathan Graff-Radford, Anna M Castillo, Val J Lowe, Michelle M Mielke, Rosebud O Roberts, Robert I Reid, David S Knopman, Clifford R Jack, Ronald C Petersen, Prashanthi Vemuri
BACKGROUND: Statins have been proposed to reduce the risk of Alzheimer's disease (AD). OBJECTIVE: Assess whether long-term statin use was associated with neuroimaging biomarkers of aging and dementia. METHODS: Methods: We analyzed neuroimaging biomarkers in 1,160 individuals aged 65+ from the Mayo Clinic Study of Aging, a population-based prospective longitudinal study of cognitive aging. RESULTS: Statin-treated (5+ years of therapy) individuals had greater burden of mid-and late-life cardiovascular disease (p <  0...
August 22, 2018: Journal of Alzheimer's Disease: JAD
Jared M Campbell, Matthew D Stephenson, Barbora de Courten, Ian Chapman, Susan M Bellman, Edoardo Aromataris
BACKGROUND: Metformin, a first line antihyperglycemic medication, is an AMPK activator and has been hypothesized to act as a geroprotective agent. Studies on its association with various classifications of age-related cognitive decline have shown mixed results with positive and negative findings. OBJECTIVE: To synthesize the best available evidence on the association of metformin-use with risk, progression, and severity of dementia. METHOD: Eligible research investigated the effect of metformin on dementia, Alzheimer's disease, or any measure of cognitive impairment compared to any control group who were not receiving metformin...
August 22, 2018: Journal of Alzheimer's Disease: JAD
Hongjuan Yuan, Wenjie Yang
To evaluate whether genetically increased serum uric acid levels influence the risk of Alzheimer's disease (AD), we used genome-wide significant single nucleotide polymorphisms for uric acid as the instrumental variables, and undertook a Mendelian randomization (MR) study to estimate the effect of uric acid on the risk of AD. The MR method prevents bias due to reverse causation (e.g., uric acid changes because of AD) and minimizes bias due to confounding of both measured and unmeasured confounders. We used the summary statistics from The International Genomics of Alzheimer's Project Consortium that is the largest AD genome-wide association study of 74,046 individuals of European ethnicity including 25,580 AD cases...
August 21, 2018: Journal of Alzheimer's Disease: JAD
John G Holden, Alexandre Cosnard, Brice Laurens, Julien Asselineau, Damien Biotti, Stéphanie Cubizolle, Sandrine Dupouy, Maıté Formaglio, Lejla Koric, Magali Seassau, Caroline Tilikete, Alain Vighetto, François Tison
Saccade alterations are potential early signs of Alzheimer's disease. However, uncertainty persists in how early and reliably automated saccade recording systems detect impairments. This multicenter pathophysiological case-control transversal study explored saccade execution in carefully diagnosed amnestic mild cognitive impairment patients fulfilling research criteria for prodromal Alzheimer's disease (n = 29), as compared to both aged-matched mild Alzheimer's disease patients (n = 23) and controls (n = 27)...
August 21, 2018: Journal of Alzheimer's Disease: JAD
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