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

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https://www.readbyqxmd.com/read/29328928/driving-cessation-over-a-24-year-period-dementia-severity-and-cerebrospinal-fluid-biomarkers
#1
Sarah H Stout, Ganesh M Babulal, Chunyu Ma, David B Carr, Denise M Head, Elizabeth A Grant, Monique M Williams, David M Holtzman, Anne M Fagan, John C Morris, Catherine M Roe
INTRODUCTION: With 36 million older adult U.S. drivers, safety is a critical concern, particularly among those with dementia. It is unclear at what stage of Alzheimer's disease (AD) older adults stop driving and whether preclinical AD affects driving cessation. METHODS: Time to driving cessation was examined based on Clinical Dementia Rating (CDR) and AD cerebrospinal fluid biomarkers. 1795 older adults followed up to 24 years received CDR ratings. A subset (591) had cerebrospinal fluid biomarker measurements and was followed up to 17 years...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29328927/alzheimer-s-disease-biomarker-guided-diagnostic-workflow-using-the-added-value-of-six-combined-cerebrospinal-fluid-candidates-a%C3%AE-1-42-total-tau-phosphorylated-tau-nfl-neurogranin-and-ykl-40
#2
Harald Hampel, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Remy Genthon, Bruno Dubois, Roberto Floris, Francesco Garaci, Simone Lista
INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29328926/dna-damage-associated-oligodendrocyte-degeneration-precedes-amyloid-pathology-and-contributes-to-alzheimer-s-and-dementia
#3
Kai-Hei Tse, Aifang Cheng, Fulin Ma, Karl Herrup
INTRODUCTION: In looking for novel non-amyloid-based etiologies for Alzheimer's disease, we explore the hypothesis that age-related myelin loss is an attractive explanation for age-associated cognitive decline and dementia. METHODS: We performed a meta-analysis of data in the National Alzheimer's Coordinating Center database accompanied by quantitative histopathology of myelin and oligodendrocytes (OLs) in frontal cortices of 24 clinically characterized individuals...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29316447/circulating-metabolites-and-general-cognitive-ability-and-dementia-evidence-from-11-cohort-studies
#4
Sven J van der Lee, Charlotte E Teunissen, René Pool, Martin J Shipley, Alexander Teumer, Vincent Chouraki, Debora Melo van Lent, Juho Tynkkynen, Krista Fischer, Jussi Hernesniemi, Andres Metspalu, Archana Singh-Manoux, Aswin Verhoeven, Gonneke Willemsen, Francien A de Leeuw, Holger Wagner, Jenny van Dongen, Johannes Hertel, Kathrin Budde, Ko Willems van Dijk, Leonie Weinhold, M Arfan Ikram, Maik Pietzner, Markus Perola, Michael Wagner, Nele Friedrich, P E Slagboom, Philip Scheltens, Qiong Yang, Robert E Gertzen, Sarah Egert, Shuo Li, Thomas Hankemeier, Catharine E M van Beijsterveldt, Vasan Ramachandran, Wolfgang Maier, Carel F W Peeters, Hans Jörgen Grabe, Alfredo Ramirez, Sudha Seshadri, Toomas Haller, Mika Kivimäki, Veikko Salomaa, Ayşe Demirkan, Dorret Boomsma, Wiesje M van der Flier, Najaf Amin, Cornelia M van Duijn
INTRODUCTION: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. METHODS: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined...
January 6, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29306584/assembly-of-809-whole-mitochondrial-genomes-with-clinical-imaging-and-fluid-biomarker-phenotyping
#5
Perry G Ridge, Mark E Wadsworth, Justin B Miller, Andrew J Saykin, Robert C Green, John S K Kauwe
INTRODUCTION: Mitochondrial genetics are an important but largely neglected area of research in Alzheimer's disease. A major impediment is the lack of data sets. METHODS: We used an innovative, rigorous approach, combining several existing tools with our own, to accurately assemble and call variants in 809 whole mitochondrial genomes. RESULTS: To help address this impediment, we prepared a data set that consists of 809 complete and annotated mitochondrial genomes with samples from the Alzheimer's Disease Neuroimaging Initiative...
January 4, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29306583/regional-vulnerability-in-alzheimer-s-the-role-of-cell-autonomous-and-transneuronal-processes
#6
Diana Acosta, Fon Powell, Yize Zhao, Ashish Raj
INTRODUCTION: The stereotypical progression of Alzheimer's disease (AD) pathology is not fully understood. The selective impact of AD on distinct regions has led the field to question if innate vulnerability exists. This study aims to determine if the causative factors of regional vulnerability are dependent on cell-autonomous or transneuronal (non-cell autonomous) processes. METHODS: Using mathematical and statistical models, we analyzed the contribution of cell-autonomous and non-cell autonomous factors to predictive linear models of AD pathology...
January 4, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29306668/a-prognostic-model-of-alzheimer-s-disease-relying-on-multiple-longitudinal-measures-and-time-to-event-data
#7
Kan Li, Richard O'Brien, Michael Lutz, Sheng Luo
INTRODUCTION: Characterizing progression in Alzheimer's disease is critically important for early detection and targeted treatment. The objective was to develop a prognostic model, based on multivariate longitudinal markers, for predicting progression-free survival in patients with mild cognitive impairment. METHODS: The information contained in multiple longitudinal markers was extracted using multivariate functional principal components analysis and used as predictors in the Cox regression models...
January 3, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29291374/af710b-an-m1-sigma-1-receptor-agonist-with-long-lasting-disease-modifying-properties-in-a-transgenic-rat-model-of-alzheimer-s-disease
#8
Hélène Hall, M Florencia Iulita, Palma Gubert, Lisi Flores Aguilar, Adriana Ducatenzeiler, Abraham Fisher, A Claudio Cuello
INTRODUCTION: AF710B (aka ANAVEX 3-71) is a novel selective allosteric M1 muscarinic and sigma-1 receptor agonist. In 3×Tg-AD mice, AF710B attenuates cognitive deficits and decreases Alzheimer-like hallmarks. We now report on the long-lasting disease-modifying properties of AF710B in McGill-R-Thy1-APP transgenic (Tg) rats. METHODS: Chronic treatment with AF710B (10 μg/kg) was initiated in postplaque 13-month-old Tg rats. Drug or vehicle was administered orally daily for 4...
December 29, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29274321/genome-wide-association-study-of-alzheimer-s-disease-endophenotypes-at-prediagnosis-stages
#9
Jaeyoon Chung, Xulong Wang, Toru Maruyama, Yiyi Ma, Xiaoling Zhang, Jesse Mez, Richard Sherva, Haruko Takeyama, Kathryn L Lunetta, Lindsay A Farrer, Gyungah R Jun
INTRODUCTION: Genetic associations for endophenotypes of Alzheimer's disease (AD) in cognitive stages preceding AD have not been thoroughly evaluated. METHODS: We conducted genome-wide association studies for AD-related endophenotypes including hippocampal volume, logical memory scores, and cerebrospinal fluid Aβ42 and total/phosphorylated tau in cognitively normal (CN), mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative study...
December 20, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29268079/midlife-cardiovascular-health-and-20-year-cognitive-decline-atherosclerosis-risk-in-communities-study-results
#10
Hector M González, Wassim Tarraf, Kimystian Harrison, B Gwen Windham, Jonathan Tingle, Alvaro Alonso, Michael Griswold, Gerardo Heiss, David Knopman, Thomas H Mosley
INTRODUCTION: The aim was to examine associations between midlife cardiovascular health (CVH) and 20-year cognitive decline among blacks and whites. METHODS: Midlife CVH metrics (American Heart Association's Life's Simple 7) were calculated and examined in relation to midlife and 20-year change in cognitive function among 13,270 whites and blacks from the Atherosclerosis Risk in Communities Cohort Study. We used linear mixed models to estimate adjusted associations of midlife CVH with midlife cognitive status and change...
December 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29268078/longitudinal-uncoupling-of-cerebral-perfusion-glucose-metabolism-and-tau-deposition-in-alzheimer-s-disease
#11
Antoine Leuzy, Elena Rodriguez-Vieitez, Laure Saint-Aubert, Konstantinos Chiotis, Ove Almkvist, Irina Savitcheva, My Jonasson, Mark Lubberink, Anders Wall, Gunnar Antoni, Agneta Nordberg
INTRODUCTION: Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single positron emission tomography study can provide both functional and molecular information. METHODS: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations...
December 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29245000/does-traumatic-brain-injury-hold-the-key-to-the-alzheimer-s-puzzle
#12
Robert E Becker, Dimitrios Kapogiannis, Nigel H Greig
INTRODUCTION: Neurodegenerative disorders have been a graveyard for hundreds of well-intentioned efforts at drug discovery and development. Concussion and other traumatic brain injuries (TBIs) and Alzheimer's disease (AD) share many overlapping pathologies and possible clinical links. METHODS: We searched the literature since 1995 using MEDLINE and Google Scholar for the terms concussion, AD, and shared neuropathologies. We also studied a TBI animal model as a supplement to transgenic (Tg) mouse AD models for evaluating AD drug efficacy by preventing neuronal losses...
December 12, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29244999/mechanical-stress-increases-brain-amyloid-%C3%AE-tau-and-%C3%AE-synuclein-concentrations-in-wild-type-mice
#13
Marcel Levy Nogueira, Minoo Hamraz, Mohammad Abolhassani, Erwan Bigan, Olivier Lafitte, Jean-Marc Steyaert, Bruno Dubois, Laurent Schwartz
INTRODUCTION: Exposure to traumatic brain injury is a core risk factor that predisposes an individual to sporadic neurodegenerative diseases. We provide evidence that mechanical stress increases brain levels of hallmark proteins associated with neurodegeneration. METHODS: Wild-type mice were exposed to multiple regimens of repetitive mild traumatic brain injury, generating a range of combinations of impact energies, frequencies, and durations of exposure. Brain concentrations of amyloid β 1-42 (Aβ1-42), total tau, and α-synuclein were measured by sandwich enzyme-linked immunosorbent assay...
December 12, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29241829/the-aged-rhesus-macaque-manifests-braak-stage-iii-iv-alzheimer-s-like-pathology
#14
Constantinos D Paspalas, Becky C Carlyle, Shannon Leslie, Todd M Preuss, Johanna L Crimins, Anita J Huttner, Christopher H van Dyck, Douglas L Rosene, Angus C Nairn, Amy F T Arnsten
INTRODUCTION: An animal model of late-onset Alzheimer's disease is needed to research what causes degeneration in the absence of dominant genetic insults and why the association cortex is particularly vulnerable to degeneration. METHODS: We studied the progression of tau and amyloid cortical pathology in the aging rhesus macaque using immunoelectron microscopy and biochemical assays. RESULTS: Aging macaques exhibited the same qualitative pattern and sequence of tau and amyloid cortical pathology as humans, reaching Braak stage III/IV...
December 11, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29233480/forecasting-the-prevalence-of-preclinical-and-clinical-alzheimer-s-disease-in-the-united-states
#15
Ron Brookmeyer, Nada Abdalla, Claudia H Kawas, María M Corrada
INTRODUCTION: We forecast the prevalence of preclinical and clinical Alzheimer's disease (AD) and evaluated potential impacts of primary and secondary preventions in the United States. METHODS: We used a multistate model incorporating biomarkers for preclinical AD with US population projections. RESULTS: Approximately 6.08 million Americans had either clinical AD or mild cognitive impairment due to AD in 2017 and that will grow to 15.0 million by 2060...
November 29, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29190460/clinical-outcomes-in-older-surgical-patients-with-mild-cognitive-impairment
#16
Annie M Racine, Tamara G Fong, Yun Gou, Thomas G Travison, Douglas Tommet, Kristen Erickson, Richard N Jones, Bradford C Dickerson, Eran Metzger, Edward R Marcantonio, Eva M Schmitt, Sharon K Inouye
INTRODUCTION: Older adults, including those with mild cognitive impairment (MCI), are increasingly undergoing surgery. METHODS: Relative risks (RRs) of MCI alone or with delirium on adverse outcomes were estimated in an ongoing prospective, observational cohort study of 560 nondemented adults aged ≥70 years. RESULTS: MCI (n = 61, 11%) was associated with increased RR of delirium (RR = 1.9, P < .001) and delirium severity (RR = 4...
November 27, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29169013/body-mass-index-and-risk-of-dementia-analysis-of-individual-level-data-from-1-3-million-individuals
#17
Mika Kivimäki, Ritva Luukkonen, G David Batty, Jane E Ferrie, Jaana Pentti, Solja T Nyberg, Martin J Shipley, Lars Alfredsson, Eleonor I Fransson, Marcel Goldberg, Anders Knutsson, Markku Koskenvuo, Eeva Kuosma, Maria Nordin, Sakari B Suominen, Töres Theorell, Eero Vuoksimaa, Peter Westerholm, Hugo Westerlund, Maria Zins, Miia Kivipelto, Jussi Vahtera, Jaakko Kaprio, Archana Singh-Manoux, Markus Jokela
INTRODUCTION: Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. METHODS: We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis...
November 20, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29156221/novel-recruitment-models-will-drive-alzheimer-s-trial-success
#18
LETTER
Eric D Vidoni, Rebecca J Bothwell, Jeffrey M Burns, John R Dwyer
No abstract text is available yet for this article.
November 20, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29161540/delirium-symptoms-are-associated-with-decline-in-cognitive-function-between-ages-53-and-69-years-findings-from-a-british-birth-cohort-study
#19
A Tsui, D Kuh, M Richards, D Davis
INTRODUCTION: Few population studies have investigated whether longitudinal decline after delirium in mid-to-late life might affect specific cognitive domains. METHODS: Participants from a birth cohort completing assessments of search speed, verbal memory, and the Addenbrooke's Cognitive Examination at age 69 were asked about delirium symptoms between ages 60 and 69 years. Linear regression models estimated associations between delirium symptoms and cognitive outcomes...
November 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29161539/home-is-where-the-future-is-the-brightfocus-foundation-consensus-panel-on-dementia-care
#20
Quincy M Samus, Constantine G Lyketsos, Betty Smith Black, Diane Bovenkamp, Michael Buckley, Christopher Callahan, Karen Davis, Laura N Gitlin, Nancy Hodgson, Deirdre Johnston, Helen C Kales, Michele Karel, John Jay Kenney, Shari M Ling, Maï Panchal, Melissa Reuland, Amber Willink
INTRODUCTION: A national consensus panel was convened to develop recommendations on future directions for home-based dementia care (HBDC). METHODS: The panel summarized advantages and challenges of shifting to HBDC as the nexus of care and developed consensus-based recommendations. RESULTS: The panel developed five core recommendations: (1) HBDC should be considered the nexus of new dementia models, from diagnosis to end of life in dementia; (2) new payment models are needed to support HBDC and reward integration of care; (3) a diverse new workforce that spans the care continuum should be prepared urgently; (4) new technologies to promote communication, monitoring/safety, and symptoms management must be tested, integrated, and deployed; and (5) targeted dissemination efforts for HBDC must be employed...
November 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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