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Alzheimer's & Dementia: the Journal of the Alzheimer's Association

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https://www.readbyqxmd.com/read/28073031/plasma-concentrations-of-free-amyloid-%C3%AE-cannot-predict-the-development-of-alzheimer-s-disease
#1
Hugo Lövheim, Fredrik Elgh, Anders Johansson, Henrik Zetterberg, Kaj Blennow, Göran Hallmans, Sture Eriksson
INTRODUCTION: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid β (Aβ)-central in the pathogenesis of AD-is a logical candidate, but studies to date have produced conflicting results on its utility. METHODS: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNOBIA plasma Aβ form assays to determine concentrations of free plasma Aβ40 and Aβ42...
January 7, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28089213/a-genome-wide-profiling-of-brain-dna-hydroxymethylation-in-alzheimer-s-disease
#2
Jinying Zhao, Yun Zhu, Jingyun Yang, Lin Li, Hao Wu, Philip L De Jager, Peng Jin, David A Bennett
INTRODUCTION: DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. METHODS: Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology...
January 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28063281/current-issues-and-future-research-priorities-for-health-economic-modelling-across-the-full-continuum-of-alzheimer-s-disease
#3
Anders Gustavsson, Colin Green, Roy W Jones, Hans Förstl, Deniz Simsek, Frederic de Reydet de Vulpillieres, Stefanie Luthman, Nicholas Adlard, Subrata Bhattacharyya, Anders Wimo
INTRODUCTION: Available data and models for the health-economic evaluation of treatment in Alzheimer's disease (AD) have limitations causing uncertainty to decision makers. Forthcoming treatment strategies in preclinical or early AD warrant an update on the challenges associated with their economic evaluation. METHODS: The perspectives of the co-authors were complemented with a targeted review of literature discussing methodological issues and data gaps in AD health-economic modelling...
January 4, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28061328/calcium-hypothesis-of-alzheimer-s-disease-and-brain-aging-a%C3%A2-framework-for-integrating-new-evidence-into-a-comprehensive-theory-of-pathogenesis
#4
(no author information available yet)
This article updates the Calcium Hypothesis of Alzheimer's disease and brain aging on the basis of emerging evidence since 1994 (The present article, with the subtitle "New evidence for a central role of Ca(2+) in neurodegeneration," includes three appendices that provide context and further explanations for the rationale for the revisions in the updated hypothesis-the three appendices are as follows: Appendix I "Emerging concepts on potential pathogenic roles of [Ca(2+)]," Appendix II "Future studies to validate the central role of dysregulated [Ca(2+)] in neurodegeneration," and Appendix III "Epilogue: towards a comprehensive hypothesis...
January 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28034600/sleep-changes-without-medial-temporal-lobe-or-brain-cortical-changes-in-community-dwelling-individuals-with-subjective-cognitive-decline
#5
Mariella Lauriola, Roberto Esposito, Stefano Delli Pizzi, Massimiliano de Zambotti, Francesco Londrillo, Joel H Kramer, Gil D Rabinovici, Armando Tartaro
INTRODUCTION: Subjective cognitive decline (SCD) is a risk factor for mild cognitive impairment (MCI) and Alzheimer disease (AD). Although sleep has been shown to be altered in MCI and AD, little is known about sleep in SCD. METHODS: Seventy cognitively normal community-dwelling participants were classified as SCD (32) or controls (38) using the Subjective Cognitive Decline Questionnaire. Sleep was assessed using actigraphy and diaries. FreeSurfer was used for performing medial temporal lobes (MTLs) and brain cortical parcellation of 3T magnetic resonance images...
December 26, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28024995/synergistic-interaction-between-amyloid-and-tau-predicts-the-progression%C3%A2-to-dementia
#6
Tharick A Pascoal, Sulantha Mathotaarachchi, Monica Shin, Andrea L Benedet, Sara Mohades, Seqian Wang, Tom Beaudry, Min Su Kang, Jean-Paul Soucy, Aurelie Labbe, Serge Gauthier, Pedro Rosa-Neto
INTRODUCTION: Recent literature proposes that amyloid-β and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia. METHODS: We stratified 314 mild cognitive impairment individuals using [(18)F]florbetapir positron emission tomography amyloid-β imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers...
December 23, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28017827/risk-of-incident-clinical-diagnosis-of-alzheimer-s-disease-type-dementia%C3%A2-attributable-to-pathology-confirmed-vascular-disease
#7
Hiroko H Dodge, Jian Zhu, Randy Woltjer, Peter T Nelson, David A Bennett, Nigel J Cairns, David W Fardo, Jeffrey A Kaye, Deniz-Erten Lyons, Nora Mattek, Julie A Schneider, Lisa C Silbert, Chengjie Xiong, Lei Yu, Frederick A Schmitt, Richard J Kryscio, Erin L Abner
INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer's disease (AD). METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts)...
December 22, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28010950/biomarker-validation-methods-and-matrix-matter
#8
LETTER
Mark Mapstone, Amrita Cheema, Xiaogang Zhong, Massimo Fiandaca, Howard Federoff
No abstract text is available yet for this article.
December 20, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27998721/exploring-the-nexus-of-alzheimer-s-disease-and-related-dementias-with-cancer-and-cancer-therapies-a-convening-of-the-alzheimer-s-association-alzheimer-s-drug-discovery-foundation
#9
REVIEW
Heather M Snyder, Tim Ahles, Stuart Calderwood, Maria C Carrillo, Honglei Chen, Chung-Chou H Chang, Suzanne Craft, Philip De Jager, Jane A Driver, Howard Fillit, David Knopman, Michael Lotze, Mary C Tierney, Suzana Petanceska, Andrew Saykin, Sudha Seshadri, Diana Shineman, Mary Ganguli
Recent population studies suggest an intriguing inverse relationship between several types of cancer and neurodegenerative diseases, including Alzheimer's disease. Understanding the intersection of the underlying biology for these two distinct families of diseases with one another may offer novel approaches to identify new therapeutic approaches and possible opportunities to repurpose existing drug candidates. The Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened a one-day workshop to delve into this discussion...
December 18, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27960092/the-vascular-impairment-of-cognition-classification-consensus-study
#10
Olivia A Skrobot, John O'Brien, Sandra Black, Christopher Chen, Charles DeCarli, Timo Erkinjuntti, Gary A Ford, Rajesh N Kalaria, Leonardo Pantoni, Florence Pasquier, Gustavo C Roman, Anders Wallin, Perminder Sachdev, Ingmar Skoog, Yoav Ben-Shlomo, Anthony P Passmore, Seth Love, Patrick G Kehoe
INTRODUCTION: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. METHODS: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study...
December 10, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27939925/a-candidate-regulatory-variant-at-the-trem-gene-cluster-associates-with-decreased-alzheimer-s-disease-risk-and-increased-treml1-and-trem2-brain-gene-expression
#11
Minerva M Carrasquillo, Mariet Allen, Jeremy D Burgess, Xue Wang, Samantha L Strickland, Shivani Aryal, Joanna Siuda, Michaela L Kachadoorian, Christopher Medway, Curtis S Younkin, Asha Nair, Chen Wang, Pritha Chanana, Daniel Serie, Thuy Nguyen, Sarah Lincoln, Kimberly G Malphrus, Kevin Morgan, Todd E Golde, Nathan D Price, Charles C White, Philip L De Jager, David A Bennett, Yan W Asmann, Julia E Crook, Ronald C Petersen, Neill R Graff-Radford, Dennis W Dickson, Steven G Younkin, Nilüfer Ertekin-Taner
INTRODUCTION: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. METHODS: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. RESULTS: A variant within a DNase hypersensitive site 5' of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6...
December 8, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27931796/the-alzheimer-s-disease-neuroimaging-initiative-3-continued-innovation-for-clinical-trial-improvement
#12
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Jennifer Salazar, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. METHODS: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis...
December 5, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27883893/circadian-alterations-during-early-stages-of-alzheimer-s-disease-are-associated-with-aberrant-cycles-of-dna-methylation-in-bmal1
#13
Peter Cronin, Michael J McCarthy, Andrew S P Lim, David P Salmon, Douglas Galasko, Eliezer Masliah, Philip L De Jager, David A Bennett, Paula Desplats
INTRODUCTION: Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, and neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and changes in DNA methylation have been reported in AD brains, but the pathways that mediate circadian deregulation in AD are incompletely understood. We hypothesized that aberrant DNA methylation may affect circadian rhythms in AD. METHODS: We investigated DNA methylation, transcription, and expression of BMAL1, a positive regulator of the circadian clock, in cultured fibroblasts and brain samples from two independent cohorts of aging and AD...
November 21, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27870939/mixed-neuropathologies-and-estimated-rates-of-clinical-progression-in-a-large-autopsy-sample
#14
Willa D Brenowitz, Rebecca A Hubbard, C Dirk Keene, Stephen E Hawes, W T Longstreth, Randy L Woltjer, Walter A Kukull
INTRODUCTION: Whether co-occurring neuropathologies interact or independently affect clinical disease progression is uncertain. We estimated rates of clinical progression and tested whether associations between clinical progression and Alzheimer's disease neuropathology (ADNP) were modified by co-occurring Lewy body disease (LBD) or vascular brain injury (VBI). METHODS: Linear mixed effects models evaluated longitudinal trends in the Clinical Dementia Rating Scale Sum of Boxes on 2046 autopsied participants seen at a U...
November 19, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27870938/evaluation-of-%C3%AE-synuclein-as-a-novel-cerebrospinal-fluid-biomarker-in-different-forms-of-prion-diseases
#15
Franc Llorens, Niels Kruse, Matthias Schmitz, Nadine Gotzmann, Ewa Golanska, Katrin Thüne, Orgeta Zejneli, Eirini Kanata, Tobias Knipper, Maria Cramm, Peter Lange, Saima Zafar, Beata Sikorska, Pawel P Liberski, Eva Mitrova, Daniela Varges, Christian Schmidt, Theodoros Sklaviadis, Brit Mollenhauer, Inga Zerr
INTRODUCTION: Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context. METHODS: We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment or dementia (n = 278), and in the neurologic control (n = 111) group...
November 18, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27825022/implementation-of-subjective-cognitive-decline-criteria-in-research-studies
#16
José L Molinuevo, Laura A Rabin, Rebecca Amariglio, Rachel Buckley, Bruno Dubois, Kathryn A Ellis, Michael Ewers, Harald Hampel, Stefan Klöppel, Lorena Rami, Barry Reisberg, Andrew J Saykin, Sietske Sikkes, Colette M Smart, Beth E Snitz, Reisa Sperling, Wiesje M van der Flier, Michael Wagner, Frank Jessen
INTRODUCTION: Subjective cognitive decline (SCD) manifesting before clinical impairment could serve as a target population for early intervention trials in Alzheimer's disease (AD). A working group, the Subjective Cognitive Decline Initiative (SCD-I), published SCD research criteria in the context of preclinical AD. To successfully apply them, a number of issues regarding assessment and implementation of SCD needed to be addressed. METHODS: Members of the SCD-I met to identify and agree on topics relevant to SCD criteria operationalization in research settings...
November 5, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27793691/glucose-level-decline-precedes-dementia-in-elderly-african-americans-with-diabetes
#17
Hugh C Hendrie, Mengjie Zheng, Wei Li, Kathleen Lane, Roberta Ambuehl, Christianna Purnell, Frederick W Unverzagt, Alexia Torke, Ashok Balasubramanyam, Chris M Callahan, Sujuan Gao
INTRODUCTION: High blood glucose levels may be responsible for the increased risk for dementia in diabetic patients. METHODS: A secondary data analysis merging electronic medical records (EMRs) with data collected from the Indianapolis-Ibadan Dementia project (IIDP). Of the enrolled 4105 African Americans, 3778 were identified in the EMR. Study endpoints were dementia, mild cognitive impairment (MCI), or normal cognition. Repeated serum glucose measurements were used as the outcome variables...
October 25, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27793643/nuclear-but-not-mitochondrial-encoded-oxphos-genes-are-altered-in-aging-mild-cognitive-impairment-and-alzheimer-s-disease
#18
Diego Mastroeni, Omar M Khdour, Elaine Delvaux, Jennifer Nolz, Gary Olsen, Nicole Berchtold, Carl Cotman, Sidney M Hecht, Paul D Coleman
INTRODUCTION: We have comprehensively described the expression profiles of mitochondrial DNA and nuclear DNA genes that encode subunits of the respiratory oxidative phosphorylation (OXPHOS) complexes (I-V) in the hippocampus from young controls, age matched, mild cognitively impaired (MCI), and Alzheimer's disease (AD) subjects. METHODS: Hippocampal tissues from 44 non-AD controls (NC), 10 amnestic MCI, and 18 AD cases were analyzed on Affymetrix Hg-U133 plus 2...
October 25, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27870940/blood-based-biomarkers-in-alzheimer-disease-current-state-of-the-science-and-a-novel-collaborative-paradigm-for-advancing-from-discovery-to-clinic
#19
Sid E O'Bryant, Michelle M Mielke, Robert A Rissman, Simone Lista, Hugo Vanderstichele, Henrik Zetterberg, Piotr Lewczuk, Holly Posner, James Hall, Leigh Johnson, Yiu-Lian Fong, Johan Luthman, Andreas Jeromin, Richard Batrla-Utermann, Alcibiades Villarreal, Gabrielle Britton, Peter J Snyder, Kim Henriksen, Paula Grammas, Veer Gupta, Ralph Martins, Harald Hampel
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art...
January 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27583652/the-worldwide-costs-of-dementia-2015-and-comparisons-with-2010
#20
Anders Wimo, Maëlenn Guerchet, Gemma-Claire Ali, Yu-Tzu Wu, A Matthew Prina, Bengt Winblad, Linus Jönsson, Zhaorui Liu, Martin Prince
INTRODUCTION: In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates. METHODS: This is a societal, prevalence-based global COI study. RESULTS: The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries...
January 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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