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

Niklas Mattsson, Philip S Insel, Michael Donohue, Jonas Jögi, Rik Ossenkoppele, Tomas Olsson, Michael Schöll, Ruben Smith, Oskar Hansson
INTRODUCTION: The relative importance of structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) to predict diagnosis and cognition in Alzheimer's disease (AD) is unclear. METHODS: We tested 56 cognitively unimpaired controls (including 27 preclinical AD), 32 patients with prodromal AD, and 39 patients with AD dementia. Optimal classifiers were constructed using the least absolute shrinkage and selection operator with 18 F-AV-1451 (tau) PET and structural MRI data (regional cortical thickness and subcortical volumes)...
January 9, 2019: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Kelsey R Thomas, Joel S Eppig, Alexandra J Weigand, Emily C Edmonds, Christina G Wong, Amy J Jak, Lisa Delano-Wood, Douglas R Galasko, David P Salmon, Steven D Edland, Mark W Bondi
INTRODUCTION: We examined reasons for low mild cognitive impairment (MCI)-to-cognitively normal (CN) reversion rates in the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: CN and MCI participants were identified as remaining stable, progressing, or reverting at 1-year of follow-up (Year 1). Application of ADNI's MCI criteria at Year 1 and Alzheimer's disease biomarkers by group were examined. RESULTS: The MCI-to-CN reversion rate was 3...
January 2, 2019: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Eliana Marisa Ramos, Deepika Reddy Dokuru, Victoria Van Berlo, Kevin Wojta, Qing Wang, Alden Y Huang, Zachary A Miller, Anna M Karydas, Eileen H Bigio, Emily Rogalski, Sandra Weintraub, Benjamin Rader, Bruce L Miller, Maria Luisa Gorno-Tempini, Marek-Marsel Mesulam, Giovanni Coppola
INTRODUCTION: Primary progressive aphasia (PPA) is a neurological syndrome, associated with both frontotemporal dementia and Alzheimer's disease, in which progressive language impairment emerges as the most salient clinical feature during the initial stages of disease. METHODS: We screened the main genes associated with Alzheimer's disease and frontotemporal dementia for pathogenic and risk variants in a cohort of 403 PPA cases. RESULTS: In this case series study, 14 (3...
December 29, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Rosalinde E R Slot, Sietske A M Sikkes, Johannes Berkhof, Henry Brodaty, Rachel Buckley, Enrica Cavedo, Efthimios Dardiotis, Francoise Guillo-Benarous, Harald Hampel, Nicole A Kochan, Simone Lista, Tobias Luck, Paul Maruff, José Luis Molinuevo, Johannes Kornhuber, Barry Reisberg, Steffi G Riedel-Heller, Shannon L Risacher, Susanne Roehr, Perminder S Sachdev, Nikolaos Scarmeas, Philip Scheltens, Melanie B Shulman, Andrew J Saykin, Sander C J Verfaillie, Pieter Jelle Visser, Stephanie J B Vos, Michael Wagner, Steffen Wolfsgruber, Frank Jessen, Wiesje M van der Flier
INTRODUCTION: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. METHODS: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. RESULTS: In SCD, incidence of dementia was 17...
December 13, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ganesh M Babulal, Yakeel T Quiroz, Benedict C Albensi, Eider Arenaza-Urquijo, Arlene J Astell, Claudio Babiloni, Alex Bahar-Fuchs, Joanne Bell, Gene L Bowman, Adam M Brickman, Gaël Chételat, Carrie Ciro, Ann D Cohen, Peggye Dilworth-Anderson, Hiroko H Dodge, Simone Dreux, Steven Edland, Anna Esbensen, Lisbeth Evered, Michael Ewers, Keith N Fargo, Juan Fortea, Hector Gonzalez, Deborah R Gustafson, Elizabeth Head, James A Hendrix, Scott M Hofer, Leigh A Johnson, Roos Jutten, Kerry Kilborn, Krista L Lanctôt, Jennifer J Manly, Ralph N Martins, Michelle M Mielke, Martha Clare Morris, Melissa E Murray, Esther S Oh, Mario A Parra, Robert A Rissman, Catherine M Roe, Octavio A Santos, Nikolaos Scarmeas, Lon S Schneider, Nicole Schupf, Sietske Sikkes, Heather M Snyder, Hamid R Sohrabi, Yaakov Stern, Andre Strydom, Yi Tang, Graciela Muniz Terrera, Charlotte Teunissen, Debora Melo van Lent, Michael Weinborn, Linda Wesselman, Donna M Wilcock, Henrik Zetterberg, Sid E O'Bryant
Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs...
December 13, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Xiaoling Zhang, Congcong Zhu, Gary Beecham, Badri N Vardarajan, Yiyi Ma, Daniel Lancour, John J Farrell, Jaeyoon Chung, Richard Mayeux, Jonathan L Haines, Gerard D Schellenberg, Margaret A Pericak-Vance, Kathryn L Lunetta, Lindsay A Farrer
INTRODUCTION: The genetic architecture of Alzheimer's disease (AD) is only partially understood. METHODS: We conducted an association study for AD using whole sequence data from 507 genetically enriched AD cases (i.e., cases having close relatives affected by AD) and 4917 cognitively healthy controls of European ancestry (EA) and 172 enriched cases and 179 controls of Caribbean Hispanic ancestry. Confirmation of top findings from stage 1 was sought in two family-based genome-wide association study data sets and in a whole genome-sequencing data set comprising members from 42 EA and 115 Caribbean Hispanic families...
November 29, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Feng Xiong, Wei Ge, Chao Ma
INTRODUCTION: We investigated the proteomic profiles of amyloid plaques (APs) from Alzheimer's disease (AD) and age-matched non-AD brains and APP/PS1 transgenic model mice. METHODS: APs and adjacent control regions were collected from fresh-frozen brain sections using laser capture dissection. Proteins were quantitated using tag-labeling coupled high-throughput mass spectra. RESULTS: Over 4000 proteins were accurately quantified, and more than 40 were identified as highly enriched in both AD and non-AD APs, including APOE, midkine, VGFR1, and complement C4...
November 28, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jenni Lehtisalo, Esko Levälahti, Jaana Lindström, Tuomo Hänninen, Teemu Paajanen, Markku Peltonen, Riitta Antikainen, Tiina Laatikainen, Timo Strandberg, Hilkka Soininen, Jaakko Tuomilehto, Miia Kivipelto, Tiia Ngandu
INTRODUCTION: Association between healthy diet and better cognition is well established, but evidence is limited to evaluate the effect of dietary changes adopted in older age. METHODS: We investigated the role of dietary changes in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) with 1260 at-risk participants (60-77 years) who were randomized to intensive multidomain intervention (including dietary counseling) or regular health advice for 2 years...
November 23, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Andrew Sommerlad, Gayan Perera, Archana Singh-Manoux, Glyn Lewis, Robert Stewart, Gill Livingston
No abstract text is available yet for this article.
November 23, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Caitlin S Latimer, Carol A Shively, C Dirk Keene, Matthew J Jorgensen, Rachel N Andrews, Thomas C Register, Thomas J Montine, Angela M Wilson, Bryan J Neth, Akiva Mintz, Joseph A Maldjian, Christopher T Whitlow, Jay R Kaplan, Suzanne Craft
INTRODUCTION: Nonhuman primates may serve as excellent models of sporadic age-associated brain β-amyloid deposition and Alzheimer's disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer's disease. METHODS: Nine middle-aged (mean = 11.2 years) and nine aged (mean = 21.7 years) female vervet/African green monkeys underwent cerebrospinal fluid collection, gait speed measurement, and neuroimaging before neuropathologic assessment...
November 19, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
W Robert Bell, Yang An, Yusuke Kageyama, Collin English, Gay L Rudow, Olga Pletnikova, Madhav Thambisetty, Richard O'Brien, Abhay R Moghekar, Marilyn S Albert, Peter V Rabins, Susan M Resnick, Juan C Troncoso
INTRODUCTION: Primary age-related tauopathy (PART) is a recently described entity that can cause cognitive impairment in the absence of Alzheimer's disease (AD). Here, we compared neuropathological features, tau haplotypes, apolipoprotein E (APOE) genotypes, and cognitive profiles in age-matched subjects with PART and AD pathology. METHODS: Brain autopsies (n = 183) were conducted on participants 85 years and older from the Baltimore Longitudinal Study of Aging and Johns Hopkins Alzheimer's Disease Research Center...
November 19, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Carla M Startin, Sarah Hamburg, Rosalyn Hithersay, Tamara Al-Janabi, Kin Y Mok, John Hardy, Andre Strydom
INTRODUCTION: Down syndrome (DS) is associated with an almost universal development of Alzheimer's disease. Individuals with DS are therefore an important population for randomized controlled trials to prevent or delay cognitive decline, though it is essential to understand the time course of early cognitive changes. METHODS: We conducted the largest cognitive study to date with 312 adults with DS to assess age-related and Alzheimer's disease-related cognitive changes during progression from preclinical to prodromal dementia, and prodromal to clinical dementia...
November 15, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ketil Oppedal, Daniel Ferreira, Lena Cavallin, Afina W Lemstra, Mara Ten Kate, Alessandro Padovani, Irena Rektorova, Laura Bonanni, Lars-Olof Wahlund, Knut Engedal, Flavio Nobili, Milica Kramberger, John-Paul Taylor, Jakub Hort, Jon Snædal, Frederic Blanc, Zuzana Walker, Angelo Antonini, Eric Westman, Dag Aarsland
INTRODUCTION: We explored regional brain atrophy patterns and their clinical correlates in dementia with Lewy bodies (DLB). METHODS: In this multicentre study, we included a total of 333 patients with DLB, 352 patients with Alzheimer's disease (AD), and 233 normal controls and used medial temporal lobe atrophy, posterior atrophy, and frontal atrophy (GCA-F) visual rating scales. Patients were classified according to four atrophy patterns. RESULTS: Patients with DLB had higher scores on all the three atrophy scales than normal controls but had less medial temporal lobe atrophy than those with AD (all P values < ...
November 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jennifer A Deal, A Richey Sharrett, Marilyn Albert, Karen Bandeen-Roche, Sheila Burgard, Sonia Davis Thomas, Rebecca F Gottesman, David Knopman, Thomas Mosley, Barbara Klein, Ronald Klein
INTRODUCTION: The easily-imaged retinal microvasculature may reflect the brain microvasculature and therefore be related to dementia. METHODS: In a population-based study of 12,482 adults aged 50-73 years (22% African American), we estimated the relationship of retinal characteristics from fundus photography (1993-1995) with incident all-cause dementia (1993-1995 to 2011-2013) and with etiologic subtype of dementia/mild cognitive impairment (2011-13). RESULTS: A total of 1259 (10%) participants developed dementia over a mean 15...
November 12, 2018: 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
Christel Claes, Johanna Van Den Daele, Ruben Boon, Sarah Schouteden, Alessio Colombo, Laura Sebastian Monasor, Mark Fiers, Laura Ordovás, FatemehArefeh Nami, Bernd Bohrmann, Sabina Tahirovic, Bart De Strooper, Catherine M Verfaillie
INTRODUCTION: Murine microglia expressing the Alzheimer's disease-linked TREM2R47H mutation display variable decrease in phagocytosis, while impaired phagocytosis is reported following loss of TREM2. However, no data exist on TREM2+/R47H human microglia. Therefore, we created human pluripotent stem cell (hPSC) monocytes and transdifferentiated microglia-like cells (tMGs) to examine the effect of the TREM2+/R47H mutation and loss of TREM2 on phagocytosis. METHODS: We generated isogenic TREM2+/R47H , TREM2+/- , and TREM2-/- hPSCs using CRISPR/Cas9...
November 7, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Richard S Isaacson, Christine A Ganzer, Hollie Hristov, Katherine Hackett, Emily Caesar, Randy Cohen, Robert Kachko, Josefina Meléndez-Cabrero, Aneela Rahman, Olivia Scheyer, Mu Ji Hwang, Cara Berkowitz, Suzanne Hendrix, Monica Mureb, Matthew W Schelke, Lisa Mosconi, Alon Seifan, Robert Krikorian
Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable lifestyle and environmental factors. We hypothesize that multimodal interventions that address many risk factors simultaneously and are individually tailored to patients may help reduce AD risk. We describe a novel clinical methodology used to evaluate and treat patients at two Alzheimer's Prevention Clinics. The framework applies evidence-based principles of clinical precision medicine to tailor individualized recommendations, follow patients longitudinally to continually refine the interventions, and evaluate N-of-1 effectiveness (trial registered at ClinicalTrials...
December 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Renee Romeo, Darshan Zala, Martin Knapp, Martin Orrell, Jane Fossey, Clive Ballard
INTRODUCTION: To examine whether an optimized intervention is a more cost-effective option than treatment as usual (TAU) for improving agitation and quality of life in nursing home residents with clinically significant agitation and dementia. METHODS: A cost-effectiveness analysis within a cluster-randomized factorial study in 69 care homes with 549 residents was conducted. Each cluster was randomized to receive either the Well-being and Health for people with Dementia (WHELD) intervention or TAU for nine months...
November 1, 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, Nathaniel A 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 25, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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