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

Zhicheng Chen, David Mengel, Ashvini Keshavan, Robert A Rissman, Andrew Billinton, Michael Perkinton, Jennifer Percival-Alwyn, Aaron Schultz, Michael Properzi, Keith Johnson, Dennis J Selkoe, Reisa A Sperling, Purvish Patel, Henrik Zetterberg, Douglas Galasko, Jonathan M Schott, Dominic M Walsh
INTRODUCTION: The tau protein plays a central role in Alzheimer's disease (AD), and there is huge interest in measuring tau in blood and cerebrospinal fluid (CSF). METHODS: We developed a set of immunoassays to measure tau in specimens from humans diagnosed based on current best clinical and CSF biomarker criteria. RESULTS: In CSF, mid-region- and N-terminal-detected tau predominated and rose in disease. In plasma, an N-terminal assay (NT1) detected elevated levels of tau in AD and AD-mild cognitive impairment (MCI)...
November 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Heather M Snyder, Roxana O Carare, Steven T DeKosky, Mony J de Leon, Derek Dykxhoorn, Li Gan, Raquel Gardner, Sidney R Hinds, Michael Jaffee, Bruce T Lamb, Susan Landau, Geoff Manley, Ann McKee, Daniel Perl, Julie A Schneider, Michael Weiner, Cheryl Wellington, Kristine Yaffe, Lisa Bain, Anthony M Pacifico, Maria C Carrillo
INTRODUCTION: In recent years, there has been growing discussion to better understand the pathophysiological mechanisms of traumatic brain injury and post-traumatic stress disorder and how they may be linked to an increased risk of neurodegenerative diseases including Alzheimer's disease in veterans. METHODS: Building on that discussion, and subsequent to a special issue of Alzheimer's & Dementia published in June 2014, which focused on military risk factors, the Alzheimer's Association convened a continued discussion of the scientific community on December 1, 2016...
November 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Lindsay R Clark, Rebecca L Koscik, Samantha L Allison, Sara E Berman, Derek Norton, Cynthia M Carlsson, Tobey J Betthauser, Barbara B Bendlin, Bradley T Christian, Nathanial Chin, Sanjay Asthana, Sterling C Johnson
BACKGROUND: This study tested if central obesity, hypertension, or depressive symptoms moderated the relationship between β-amyloid (Aβ) and longitudinal cognitive performance in late middle-aged adults enriched for Alzheimer's disease (AD) risk. METHODS: Participants (n = 207; ages = 40-70 years; 73% parental AD) in the Wisconsin Registry for Alzheimer's Prevention study completed 3+ neuropsychological evaluations and a [11 C]PiB positron emission tomography scan or lumbar puncture...
October 24, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Catherine W Striley, Sadaf A Milani, Evan Kwiatkowski, Steven T DeKosky, Linda B Cottler
INTRODUCTION: Research progress on neurocognitive disorders requires donation of both healthy and diseased brains. Here, we describe attitudes toward brain donation among a large community sample in Florida. METHODS: HealthStreet, a community engagement program at the University of Florida, used community health workers to assess community attitudes toward research participation, including brain donation. RESULTS: Over 60% of people, primarily Caucasian and employed, indicated that they would be likely or somewhat likely to donate their brain for research...
October 23, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Sebastian Palmqvist, Philip S Insel, Henrik Zetterberg, Kaj Blennow, Britta Brix, Erik Stomrud, Niklas Mattsson, Oskar Hansson
INTRODUCTION: The aim was to create readily available algorithms that estimate the individual risk of β-amyloid (Aβ) positivity. METHODS: The algorithms were tested in BioFINDER (n = 391, subjective cognitive decline or mild cognitive impairment) and validated in Alzheimer's Disease Neuroimaging Initiative (n = 661, subjective cognitive decline or mild cognitive impairment). The examined predictors of Aβ status were demographics; cognitive tests; white matter lesions; apolipoprotein E (APOE); and plasma Aβ42 /Aβ40 , tau, and neurofilament light...
October 23, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Renaud La Joie, Nagehan Ayakta, William W Seeley, Ewa Borys, Adam L Boxer, Charles DeCarli, Vincent Doré, Lea T Grinberg, Eric Huang, Ji-Hye Hwang, Milos D Ikonomovic, Clifford Jack, William J Jagust, Lee-Way Jin, William E Klunk, Julia Kofler, Orit H Lesman-Segev, Samuel N Lockhart, Val J Lowe, Colin L Masters, Chester A Mathis, Catriona L McLean, Bruce L Miller, Daniel Mungas, James P O'Neil, John M Olichney, Joseph E Parisi, Ronald C Petersen, Howard J Rosen, Christopher C Rowe, Salvatore Spina, Prashanthi Vemuri, Victor L Villemagne, Melissa E Murray, Gil D Rabinovici
INTRODUCTION: We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [11 C]PIB-positron emission tomography ([11 C]PIB-PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification. METHODS: Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings. RESULTS: CL values increased with each CERAD neuritic plaque score increment (median -3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases...
October 19, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Tim Wilkinson, Kathryn Bush, Cathie L M Sudlow
No abstract text is available yet for this article.
October 16, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Giovanni B Frisoni, Frederik Barkhof, Daniele Altomare, Johannes Berkhof, Marina Boccardi, Elisa Canzoneri, Lyduine Collij, Alexander Drzezga, Gill Farrar, Valentina Garibotto, Rossella Gismondi, Juan-Domingo Gispert, Frank Jessen, Miia Kivipelto, Isadora Lopes Alves, José-Luis Molinuevo, Agneta Nordberg, Pierre Payoux, Craig Ritchie, Irina Savicheva, Philip Scheltens, Mark E Schmidt, Jonathan Schott, Andrew Stephens, Bart van Berckel, Bruno Vellas, Zuzana Walker, Nicola Raffa
INTRODUCTION: Reimbursement of amyloid-PET is lagging due to the lack of definitive evidence on its clinical utility and cost-effectiveness. The Amyloid Imaging to Prevent Alzheimer's Disease-Diagnostic and Patient Management Study (AMYPAD-DPMS) is designed to fill this gap. METHODS: AMYPAD-DPMS is a phase 4, multicenter, prospective, randomized controlled study. Nine hundred patients with subjective cognitive decline plus, mild cognitive impairment, and dementia possibly due to Alzheimer's disease will be randomized to ARM1, amyloid-PET performed early in the diagnostic workup; ARM2, amyloid-PET performed after 8 months; and ARM3, amyloid-PET performed whenever the physician chooses to do so...
October 16, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Kwangsik Nho, Alexandra Kueider-Paisley, Siamak MahmoudianDehkordi, Matthias Arnold, Shannon L Risacher, Gregory Louie, Colette Blach, Rebecca Baillie, Xianlin Han, Gabi Kastenmüller, Wei Jia, Guoxiang Xie, Shahzad Ahmad, Thomas Hankemeier, Cornelia M van Duijn, John Q Trojanowski, Leslie M Shaw, Michael W Weiner, P Murali Doraiswamy, Andrew J Saykin, Rima Kaddurah-Daouk
INTRODUCTION: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-β deposition. METHOD: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18 F]FDG PET)...
October 15, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Xiaochen Hu, Charlotte E Teunissen, Annika Spottke, Michael T Heneka, Emrah Düzel, Oliver Peters, Siyao Li, Josef Priller, Katharina Buerger, Stefan Teipel, Christoph Laske, Sander C J Verfaillie, Frederik Barkhof, Nina Coll-Padrós, Lorena Rami, Jose Luis Molinuevo, Wiesje M van der Flier, Frank Jessen
INTRODUCTION: Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. METHODS: We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona)...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Dallas P Veitch, Michael W Weiner, 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, 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 is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials. METHODS: We used standard methods to identify nearly 600 publications using ADNI data from 2016 and 2017 (listed in Supplementary material and searchable at http://adni...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Fang Huang, Minghui Wang, Rong Liu, Jian-Zhi Wang, Eric Schadt, Vahram Haroutunian, Pavel Katsel, Bin Zhang, Xiaochuan Wang
INTRODUCTION: Altered cell cycle reentry has been observed in Alzheimer's disease (AD). DTL was predicted as the top driver of a cell cycle subnetwork associated with AD. METHODS: We systematically investigated DTL expression in AD and studied the molecular, cellular, and behavioral endophenotypes triggered by DTL overexpression. RESULTS: We experimentally validated that CDT2, the protein encoded by DTL, activated CDKs through downregulating P21, which induced tau hyperphosphorylation and Aβ toxicity, two hallmarks of AD...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Priya Palta, A Richey Sharrett, Jennifer A Deal, Kelly R Evenson, Kelley Pettee Gabriel, Aaron R Folsom, Alden L Gross, B Gwen Windham, David Knopman, Thomas H Mosley, Gerardo Heiss
INTRODUCTION: We tested the hypotheses that higher levels of and persistence of midlife leisure-time physical activity (LTPA) for a long term are associated with lower cognitive decline and less incident dementia. METHODS: A total of 10,705 participants (mean age: 60 years) had LTPA (no, low, middle, or high) measured in 1987-1989 and 1993-1995. LTPA was assessed in relation to incident dementia and 14-year change in general cognitive performance. RESULTS: Over a median follow-up of 17...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Melissa Lamar, Lei Yu, Leah H Rubin, Bryan D James, Lisa L Barnes, Jose Marcelo Farfel, Chris Gaiteri, Aron S Buchman, David A Bennett, Julie A Schneider
INTRODUCTION: Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology. METHODS: We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding ε2/ε4 carriers, multivariable regressions for each CVD-related neuropathology compared ε4 and ε2 carriers to ε3/ε3 carriers adjusting for confounders including age and Alzheimer's neuropathology...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Åsa Sandelius, Erik Portelius, Åsa Källén, Henrik Zetterberg, Uros Rot, Bob Olsson, Jon B Toledo, Leslie M Shaw, Virginia M Y Lee, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David A Wolk, Leo McCluskey, Lauren Elman, Vesna Kostanjevecki, Manu Vandijck, Jennifer McBride, John Q Trojanowski, Kaj Blennow
INTRODUCTION: The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection. METHODS: We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344)...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Robert D Moir, Richard Lathe, Rudolph E Tanzi
OBJECTIVE: We explore here a novel model for amyloidogenesis in Alzheimer's disease (AD). This new perspective on AD amyloidosis seeks to provide a rational framework for incorporating recent and seemingly independent findings on the antimicrobial role of β-amyloid and emerging experimental, genetic, and epidemiological data, suggesting innate immune-mediated inflammation propagates AD neurodegeneration. BACKGROUND: AD pathology is characterized by cerebral deposition of amyloid-β protein (Aβ) as β-amyloid...
October 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Siamak MahmoudianDehkordi, Matthias Arnold, Kwangsik Nho, Shahzad Ahmad, Wei Jia, Guoxiang Xie, Gregory Louie, Alexandra Kueider-Paisley, M Arthur Moseley, J Will Thompson, Lisa St John Williams, Jessica D Tenenbaum, Colette Blach, Rebecca Baillie, Xianlin Han, Sudeepa Bhattacharyya, Jon B Toledo, Simon Schafferer, Sebastian Klein, Therese Koal, Shannon L Risacher, Mitchel Allan Kling, Alison Motsinger-Reif, Daniel M Rotroff, John Jack, Thomas Hankemeier, David A Bennett, Philip L De Jager, John Q Trojanowski, Leslie M Shaw, Michael W Weiner, P Murali Doraiswamy, Cornelia M van Duijn, Andrew J Saykin, Gabi Kastenmüller, Rima Kaddurah-Daouk
INTRODUCTION: Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD). METHODS: Serum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative...
October 8, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Leslie M Shaw, Jalayne Arias, Kaj Blennow, Douglas Galasko, Jose Luis Molinuevo, Stephen Salloway, Suzanne Schindler, Maria C Carrillo, James A Hendrix, April Ross, Judit Illes, Courtney Ramus, Sheila Fifer
INTRODUCTION: The Alzheimer's Association convened a multidisciplinary workgroup to develop appropriate use criteria to guide the safe and optimal use of the lumbar puncture procedure and cerebrospinal fluid (CSF) testing for Alzheimer's disease pathology detection in the diagnostic process. METHODS: The workgroup, experienced in the ethical use of lumbar puncture and CSF analysis, developed key research questions to guide the systematic review of the evidence and developed clinical indications commonly encountered in clinical practice based on key patient groups in whom the use of lumbar puncture and CSF may be considered as part of the diagnostic process...
October 3, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Cara M Altimus, Kirstie Keller, Patrick Brannelly, Erin Ross, Chang-Ting Lin, Ekemini A U Riley, LaTese Briggs, Jeremy Smith, Melissa Stevens
Neurodegenerative diseases encompass a range of diagnoses, such as Alzheimer's disease and Parkinson's disease. Despite decades of advancements in understanding the neurobiology of individual diseases, this class has few disease-modifying therapeutics and a paucity of biomarkers for diagnosis or progression. However, tau protein aggregation has emerged as a potential unifying factor across several neurodegenerative diseases, which has prompted a rapid growth in tau-related funding. In spite of this growth, research funding in this area is not in line with the immense magnitude of disease burden, and drug discovery and clinical research remain underfunded...
October 3, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Mary Sano, Susan Egelko, Carolyn W Zhu, Clara Li, Michael C Donohue, Steven Ferris, Jeffrey Kaye, James C Mundt, Chung-Kai Sun, Paul S Aisen, Howard H Feldman
INTRODUCTION: Little is known about factors affecting motivation and satisfaction of participants in dementia prevention trials. METHODS: A Research Satisfaction Survey was administered to 422 nondemented older adults who participated in the Home-Based Assessment trial. RESULTS: Overall satisfaction was high, with means of all individual items near to above a value of 3 on a scale from 1 (worst) to 4 (best). Greater satisfaction was associated with staff-administered interviews versus automated technologies...
October 3, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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