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

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https://www.readbyqxmd.com/read/27931796/the-alzheimer-s-disease-neuroimaging-initiative-3-continued-innovation-for-clinical-trial-improvement
#1
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
#2
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/27870940/blood-based-biomarkers-in-alzheimer-disease-current-state-of-the-science-and-a-novel-collaborative-paradigm-for-advancing-from-discovery-to-clinic
#3
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...
November 18, 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
#4
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 Sum of Boxes on 2046 autopsied participants seen at a U...
November 18, 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
#5
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
#6
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
#7
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
#8
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/27770636/two-novel-loci-cobl-and-slc10a2-for-alzheimer-s-disease-in-african-americans
#9
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 20, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27770635/hemodynamic-and-serum-cardiac-markers-and-risk-of-cognitive-impairment-and-dementia
#10
REVIEW
Isabelle F van der Velpen, Stephanie Feleus, Anne Suzanne Bertens, Behnam Sabayan
INTRODUCTION: Cardiac function is a key player in maintaining energy homeostasis in the brain. Heart failure is closely related to higher risk of neurocognitive disorders. Recent evidence shows that this relationship might not be limited to patients with advanced heart failure, and even suboptimal cardiac functioning is associated with accelerated brain aging. Hence, hemodynamic and serum cardiac markers may provide valuable information about the risk of dementia. METHODS: We provide an overview on the link between cardiac markers and cognitive function by a systematic search in five databases...
October 19, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27755974/neuronal-exosomes-reveal-alzheimer-s-disease-biomarkers-in-down-syndrome
#11
Eric D Hamlett, Edward J Goetzl, Aurélie Ledreux, Vitaly Vasilevko, Heather A Boger, Angela LaRosa, David Clark, Steven L Carroll, María Carmona-Iragui, Juan Fortea, Elliott J Mufson, Marwan Sabbagh, Abdul H Mohammed, Dean Hartley, Eric Doran, Ira T Lott, Ann-Charlotte Granholm
INTRODUCTION: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD. METHODS: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls...
October 15, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27750032/prevention-of-tau-increase-in-cerebrospinal-fluid-of-app-transgenic-mice-suggests-downstream-effect-of-bace1-inhibition
#12
Juliane Schelle, Lisa Häsler, Jens C Göpfert, Thomas O Joos, Hugo Vanderstichele, Erik Stoops, Ulf Neumann, Derya R Shimshek, Matthias Staufenbiel, Mathias Jucker, Stephan A Kaeser
INTRODUCTION: The inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of Aβ precursor protein (APP) transgenic mice. METHODS: APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high-sensitivity tau sandwich immunoassay was developed...
October 14, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27743520/characterizing-familial-corticobasal-syndrome-due-to-alzheimer-s-pathology-and-psen1-mutations
#13
Benjamin Lam, Aun Khan, Julia Keith, Ekaterina Rogaeva, Juan Bilbao, Peter St George-Hyslop, Mahdi Ghani, Morris Freedman, Donald T Stuss, Tiffany Chow, Sandra E Black, Mario Masellis
INTRODUCTION: Corticobasal syndrome (CBS) resulting from genetic Alzheimer's disease (AD) has been described only once. Whether familial CBS-AD is a distinct clinical entity with its own imaging signature remains unknown. METHODS: Four individuals with CBS from two families underwent detailed assessment. For two individuals, regional atrophy and hypoperfusion were compared to autopsy-confirmed typical late-onset AD and corticobasal degeneration, as well as genetically proven PSEN1 cases with an amnestic presentation...
October 12, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27702619/recommended-cognitive-outcomes-in-preclinical-alzheimer-s-disease-consensus-statement-from-the-european-prevention-of-alzheimer-s-dementia-project
#14
Karen Ritchie, Michael Ropacki, B Albala, John Harrison, Jeffrey Kaye, Joel Kramer, Christopher Randolph, C W Ritchie
The Horizon 2020/IMI European Prevention of Alzheimer's Dementia (EPAD) project will undertake large-scale proof-of-concept trials in predementia AD. Within EPAD, the monitoring of cognitive trajectories in the preclinical period will constitute a central outcome measure; however, there are currently no clear guidelines as to how this should be achieved as most measures have been developed for the period around dementia diagnosis. The EPAD Scientific Advisory Group for Clinical and Cognitive Outcomes identified appropriate cognitive measures based on a literature search covering both cognitive correlates of preclinical brain changes from imaging studies and cognitive changes observed over time in nondementia population cohorts developing incident dementia...
October 1, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27702618/detecting-cognitive-changes-in-preclinical-alzheimer-s-disease-a-review-of-its-feasibility
#15
REVIEW
Marion Mortamais, Jessica A Ash, John Harrison, Jeffrey Kaye, Joel Kramer, Christopher Randolph, Carine Pose, Bruce Albala, Michael Ropacki, Craig W Ritchie, Karen Ritchie
Significant progress has been made in characterizing the biological changes occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been viewed, however, as a late-stage phenomenon, despite increasing evidence that changes may be detected in the decades preceding dementia. In the absence of comprehensive evidence-based guidelines for preclinical cognitive assessment, longitudinal cohort and neuroimaging studies have been reviewed to determine the temporal order and brain biomarker correlates of specific cognitive functions...
October 1, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27697430/defining-imaging-biomarker-cut-points-for-brain-aging-and-alzheimer-s-disease
#16
Clifford R Jack, Heather J Wiste, Stephen D Weigand, Terry M Therneau, Val J Lowe, David S Knopman, Jeffrey L Gunter, Matthew L Senjem, David T Jones, Kejal Kantarci, Mary M Machulda, Michelle M Mielke, Rosebud O Roberts, Prashanthi Vemuri, Denise A Reyes, Ronald C Petersen
INTRODUCTION: Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness. METHODS: We examined five methods for determining cut points. RESULTS: The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness...
September 30, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27693185/mtor-and-neuronal-cell-cycle-reentry-how-impaired-brain-insulin-signaling-promotes-alzheimer-s-disease
#17
Andrés Norambuena, Horst Wallrabe, Lloyd McMahon, Antonia Silva, Eric Swanson, Shahzad S Khan, Daniel Baerthlein, Erin Kodis, Salvatore Oddo, James W Mandell, George S Bloom
A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles...
September 29, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27693189/longitudinal-brain-structural-changes-in-preclinical-alzheimer-disease
#18
Jordi Pegueroles, Eduard Vilaplana, Victor Montal, Frederic Sampedro, Daniel Alcolea, Maria Carmona-Iragui, Jordi Clarimon, Rafael Blesa, Alberto Lleó, Juan Fortea
BACKGROUND: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood. METHODS: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates. RESULTS: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27693188/a-common-challenge-in-older-adults-classification-overlap-and-therapy-of-depression-and-dementia
#19
REVIEW
Thomas Leyhe, Charles F Reynolds, Tobias Melcher, Christoph Linnemann, Stefan Klöppel, Kaj Blennow, Henrik Zetterberg, Bruno Dubois, Simone Lista, Harald Hampel
Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27693187/subjective-cognitive-decline-in-cognitively-normal-elders-from-the-community-or-from-a-memory-clinic-differential-affective-and-imaging-correlates
#20
Audrey Perrotin, Renaud La Joie, Vincent de La Sayette, Louisa Barré, Florence Mézenge, Justine Mutlu, Denis Guilloteau, Stéphanie Egret, Francis Eustache, Gaël Chételat
INTRODUCTION: Subjective cognitive decline (SCD) could indicate preclinical Alzheimer's disease, but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic. METHODS: We compared 28 patients from a memory clinic with isolated SCD, 35 community-recruited elders with similarly high levels of self-reported cognitive difficulties, and 35 community-recruited controls with low self-reported cognitive difficulties...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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