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

Michael Navitsky, Abhinay D Joshi, Ian Kennedy, William E Klunk, Christopher C Rowe, Dean F Wong, Michael J Pontecorvo, Mark A Mintun, Michael D Devous
INTRODUCTION: Klunk et al. recently proposed a means of standardizing quantitation of amyloid burden from positron emission tomography scans to a common Centiloid scale, and we have applied that method to florbetapir. METHODS: Florbetapir and Pittsburgh compound B scans were acquired for 46 mixed clinical presentation subjects within 18 ± 20 days. Florbetapir and Pittsburgh compound B cortical standardized uptake value ratio (SUVr) values were well correlated for both standard Centiloid (R2  = 0...
July 10, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Kathleen M Hayden, Sharon K Inouye, Colm Cunningham, Richard N Jones, Michael Avidan, Daniel Davis, George Kuchel, Ara S Khachaturian
No abstract text is available yet for this article.
June 27, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Myuri Ruthirakuhan, Krista L Lanctôt, Matteo Di Scipio, Mehnaz Ahmed, Nathan Herrmann
INTRODUCTION: Agitation is one of the most challenging neuropsychiatric symptoms to treat in Alzheimer's disease and has significant implications for patient and caregiver. A major source of difficulty in identifying safe and effective treatments for agitation is the lack of validated biomarkers. As such, patients may not be appropriately targeted, and biological response to pharmacotherapy cannot be adequately monitored. METHODS: This systematic review aimed to summarize evidence on the association between biomarkers and agitation/aggression in patients with Alzheimer's disease, utilizing the National Institute on Aging-Alzheimer's Association Research Framework and the Biomarkers, EndpointS, and other Tools Resource of the Food and Drug Association-National Institutes of Health Biomarker Working Group...
June 22, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Oskar Hansson, Alvydas Mikulskis, Anne M Fagan, Charlotte Teunissen, Henrik Zetterberg, Hugo Vanderstichele, Jose Luis Molinuevo, Leslie M Shaw, Manu Vandijck, Marcel M Verbeek, Mary Savage, Niklas Mattsson, Piotr Lewczuk, Richard Batrla, Sandra Rutz, Robert A Dean, Kaj Blennow
INTRODUCTION: Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. METHODS: This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. RESULTS: The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation...
June 22, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Han Soo Yoo, Seun Jeon, Seok Jong Chung, Alan C Evans, Mijin Yun, Phil Hyu Lee, Young Ho Sohn, Byoung Seok Ye
INTRODUCTION: Olfactory dysfunction is common in Alzheimer's disease- and Lewy body-related disorders, but its neural correlates have not been clearly elucidated. METHODS: We retrospectively recruited 237 patients with Alzheimer's disease-related cognitive impairment (ADCI) and 217 with Lewy body-related cognitive impairment (LBCI). They were identically evaluated using the Cross-Cultural Smell Identification Test, neuropsychological tests, and brain magnetic resonance imaging...
June 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Stefan Teipel, Alexandra König, Jesse Hoey, Jeff Kaye, Frank Krüger, Julie M Robillard, Thomas Kirste, Claudio Babiloni
Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials...
June 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jeffrey Cummings
INTRODUCTION: The National Institute on Aging-Alzheimer's Association Research Framework on Alzheimer's disease (AD) represents an important advance in the biological characterization of the AD spectrum. METHODS: The National Institute on Aging-Alzheimer's Association Framework is considered as it applies to clinical trials. RESULTS: Using the combination of amyloid (A), tau (T), and neurodegeneration (N) biomarkers, the Framework provides a means of defining the state of patients with regard to Alzheimer pathologic change...
June 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Xinxin Guo, Svante Östling, Silke Kern, Lena Johansson, Ingmar Skoog
INTRODUCTION: Longitudinal studies are needed to understand the long-term associations between stroke and dementia. METHODS: A population sample of 1460 women without stroke or dementia at baseline was followed over 44 years, from 1968 to 2012. Information on stroke and dementia was obtained from neuropsychiatric examinations, key-informant interviews, hospital registry, and medical records. RESULTS: During 44 years follow-up, 362 women developed stroke and 325, dementia...
June 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Lana Fani, Frank J Wolters, M Kamran Ikram, Marco J Bruno, Albert Hofman, Peter J Koudstaal, Sarwa Darwish Murad, M Arfan Ikram
INTRODUCTION: Helicobacter pylori infection might increase risk of dementia, but available evidence is inconsistent, and longitudinal studies are sparse. We investigated the association between H. pylori serology and dementia risk in a population-based cohort. METHODS: Between 1997 and 2002, we measured H. pylori serum IgG titers in 4215 nondemented participants of the Rotterdam Study with a mean age of 69 years. We determined the association between H. pylori at baseline and dementia incidence until 2015, per natural log (U/mL) increase in titer, and for seropositive/seronegative, using Cox models adjusting for cohort, sex, age, education, and cardiovascular risk factors...
June 20, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Julie M Robillard, Ian Cleland, Jesse Hoey, Chris Nugent
INTRODUCTION: Technology interventions are showing promise to assist persons with dementia and their carers. However, low adoption rates for these technologies and ethical considerations have impeded the realization of their full potential. METHODS: Building on recent evidence and an iterative framework development process, we propose the concept of "ethical adoption": the deep integration of ethical principles into the design, development, deployment, and usage of technology...
June 19, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Rebecca A Nebel, Neelum T Aggarwal, Lisa L Barnes, Aimee Gallagher, Jill M Goldstein, Kejal Kantarci, Monica P Mallampalli, Elizabeth C Mormino, Laura Scott, Wai Haung Yu, Pauline M Maki, Michelle M Mielke
INTRODUCTION: Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches. METHODS: The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD...
May 31, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Rachel F Buckley, Elizabeth C Mormino, Rebecca E Amariglio, Michael J Properzi, Jennifer S Rabin, Yen Ying Lim, Kathryn V Papp, Heidi I L Jacobs, Samantha Burnham, Bernard J Hanseeuw, Vincent Doré, Annette Dobson, Colin L Masters, Michael Waller, Christopher C Rowe, Paul Maruff, Michael C Donohue, Dorene M Rentz, Dylan Kirn, Trey Hedden, Jasmeer Chhatwal, Aaron P Schultz, Keith A Johnson, Victor L Villemagne, Reisa A Sperling
INTRODUCTION: Our objective was to investigate the effect of sex on cognitive decline within the context of amyloid β (Aβ) burden and apolipoprotein E genotype. METHODS: We analyzed sex-specific effects on Aβ-positron emission tomography, apolipoprotein, and rates of change on the Preclinical Alzheimer Cognitive Composite-5 across three cohorts, such as the Alzheimer's Disease Neuroimaging Initiative, Australian Imaging, Biomarker and Lifestyle, and Harvard Aging Brain Study (n = 755; clinical dementia rating = 0; age (standard deviation) = 73...
May 24, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Bernard J Hanseeuw, Rebecca A Betensky, Elizabeth C Mormino, Aaron P Schultz, Jorge Sepulcre, John A Becker, Heidi I L Jacobs, Rachel F Buckley, Molly R LaPoint, Patrizia Vanini, Nancy J Donovan, Jasmeer P Chhatwal, Gad A Marshall, Kathryn V Papp, Rebecca E Amariglio, Dorene M Rentz, Reisa A Sperling, Keith A Johnson
INTRODUCTION: Amyloid PET data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. METHODS: We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition...
May 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Stefan J Teipel, Enrica Cavedo, Simone Lista, Marie-Odile Habert, Marie-Claude Potier, Michel J Grothe, Stephane Epelbaum, Luisa Sambati, Geoffroy Gagliardi, Nicola Toschi, Michael Greicius, Bruno Dubois, Harald Hampel
INTRODUCTION: Cognitive change in people at risk of Alzheimer's disease (AD) such as subjective memory complainers is highly variable across individuals. METHODS: We used latent class growth modeling to identify distinct classes of nonlinear trajectories of cognitive change over 2 years follow-up from 265 subjective memory complainers individuals (age 70 years and older) of the INSIGHT-preAD cohort. We determined the effect of cortical amyloid load, hippocampus and basal forebrain volumes, and education on the cognitive trajectory classes...
May 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Kristin Aaser Lunde, Janete Chung, Ingvild Dalen, Kenn Freddy Pedersen, Jan Linder, Magdalena E Domellöf, Eva Elgh, Angus D Macleod, Charalampos Tzoulis, Jan Petter Larsen, Ole-Bjørn Tysnes, Lars Forsgren, Carl E Counsell, Guido Alves, Jodi Maple-Grødem
INTRODUCTION: Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. METHODS: Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis...
May 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Daniel Bos, Frank J Wolters, Sirwan K L Darweesh, Meike W Vernooij, Frank de Wolf, M Arfan Ikram, Albert Hofman
INTRODUCTION: Cerebral small vessel disease is increasingly linked to dementia. METHODS: We systematically searched Medline, Embase, and Cochrane databases for prospective population-based studies addressing associations of white matter hyperintensities, covert brain infarcts (i.e., clinically silent infarcts), and cerebral microbleeds with risk of all-dementia or Alzheimer's disease and performed meta-analyses. RESULTS: We identified 11 studies on white matter hyperintensities, covert brain infarcts, or cerebral microbleeds with risk of all-dementia or Alzheimer's disease...
May 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jenny U Johansson, William D Brubaker, Harold Javitz, Andrew W Bergen, Denise Nishita, Abhishek Trigunaite, Andrés Crane, Justine Ceballos, Diego Mastroeni, Andrea J Tenner, Marwan Sabbagh, Joseph Rogers
INTRODUCTION: Genome-wide association studies consistently show that single nucleotide polymorphisms (SNPs) in the complement receptor 1 (CR1) gene modestly but significantly alter Alzheimer's disease (AD) risk. Follow-up research has assumed that CR1 is expressed in the human brain despite a paucity of evidence for its function there. Alternatively, erythrocytes contain >80% of the body's CR1, where, in primates, it is known to bind circulating pathogens. METHODS: Multidisciplinary methods were employed...
May 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Usman Saeed, Saira S Mirza, Bradley J MacIntosh, Nathan Herrmann, Julia Keith, Joel Ramirez, Sean M Nestor, Qinggang Yu, Jo Knight, Walter Swardfager, Steven G Potkin, Ekaterina Rogaeva, Peter St George-Hyslop, Sandra E Black, Mario Masellis
INTRODUCTION: Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored. METHODS: We studied 298 patients (AD = 250, DLB = 48; 38 autopsy confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE-ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis...
May 18, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
David S Knopman, Rebecca F Gottesman, A Richey Sharrett, Amanda L Tapia, Sonia DavisThomas, B Gwen Windham, Laura Coker, Andrea L C Schneider, Alvaro Alonso, Josef Coresh, Marilyn S Albert, Thomas H Mosley
INTRODUCTION: The interplay between midlife vascular risk factors and midlife cognitive function with later life mild cognitive impairment (MCI) and dementia (DEM) is not well understood. METHODS: In the Atherosclerosis Risk in Communities Study, cardiovascular risk factors and cognition were assessed in midlife, ages 45-64 years. In 2011-2013, 20-25 years later, all consenting Atherosclerosis Risk in Communities participants underwent a cognitive and neurological evaluation and were given adjudicated diagnoses of cognitively normal, MCI, or DEM...
May 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Michael W Weiner, Rachel Nosheny, Monica Camacho, Diana Truran-Sacrey, R Scott Mackin, Derek Flenniken, Aaron Ulbricht, Philip Insel, Shannon Finley, Juliet Fockler, Dallas Veitch
INTRODUCTION: Recruitment, assessment, and longitudinal monitoring of participants for neuroscience studies and clinical trials limit the development of new treatments. Widespread Internet use allows data capture from participants in an unsupervised setting. The Brain Health Registry, a website and online registry, collects data from participants and their study partners. METHODS: The Brain Health Registry obtains self and study partner report questionnaires and neuropsychological data, including the Cogstate Brief Battery, Lumos Labs Neurocognitive Performance Test, and MemTrax Memory Test...
May 8, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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