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

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https://www.readbyqxmd.com/read/28343848/capillary-dysfunction-is-associated-with-symptom-severity-and-neurodegeneration-in-alzheimer-s-disease
#1
Rune B Nielsen, Lærke Egefjord, Hugo Angleys, Kim Mouridsen, Michael Gejl, Arne Møller, Birgitte Brock, Hans Brændgaard, Hanne Gottrup, Jørgen Rungby, Simon F Eskildsen, Leif Østergaard
INTRODUCTION: We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning. METHODS: Thirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2)...
March 23, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#2
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, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28341540/clinical-meaningfulness-of-alzheimer-s-disease-assessment-scale-cognitive-subscale-change-in-relation-to-goal-attainment-in-patients-on-cholinesterase-inhibitors
#3
Kenneth Rockwood, Susan E Howlett, Deborah Hoffman, Rachel Schindler, Arnold Mitnitski
INTRODUCTION: The clinical meaningfulness of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) subscore change is disputed. We compared 2- to 4-point ADAS-Cog changes with changes in Goal Attainment Scaling (GAS) and everyday function across initial ADAS-Cog scores and treatment responses. METHODS: This exploratory analysis evaluated mild-moderate Alzheimer's disease patients treated with donepezil (12 months) or galantamine (8 months). Clinical meaningfulness was defined as concomitant ADAS-Cog and GAS changes of ±3 points and/or functional improvement...
March 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28341160/metabolic-network-failures-in-alzheimer-s-disease-a-biochemical-road%C3%A2-map
#4
Jon B Toledo, Matthias Arnold, Gabi Kastenmüller, Rui Chang, Rebecca A Baillie, Xianlin Han, Madhav Thambisetty, Jessica D Tenenbaum, Karsten Suhre, J Will Thompson, Lisa St John-Williams, Siamak MahmoudianDehkordi, Daniel M Rotroff, John R Jack, Alison Motsinger-Reif, Shannon L Risacher, Colette Blach, Joseph E Lucas, Tyler Massaro, Gregory Louie, Hongjie Zhu, Guido Dallmann, Kristaps Klavins, Therese Koal, Sungeun Kim, Kwangsik Nho, Li Shen, Ramon Casanova, Sudhir Varma, Cristina Legido-Quigley, M Arthur Moseley, Kuixi Zhu, Marc Y R Henrion, Sven J van der Lee, Amy C Harms, Ayse Demirkan, Thomas Hankemeier, Cornelia M van Duijn, John Q Trojanowski, Leslie M Shaw, Andrew J Saykin, Michael W Weiner, P Murali Doraiswamy, Rima Kaddurah-Daouk
INTRODUCTION: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance...
March 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28315661/nutrient-biomarker-patterns-and-long-term-risk-of-dementia-in-older-adults
#5
Camille Amadieu, Sophie Lefèvre-Arbogast, Cécile Delcourt, Jean-François Dartigues, Catherine Helmer, Catherine Féart, Cécilia Samieri
INTRODUCTION: Several nutrients may predict dementia risk. We characterized nutrient biomarker patterns, which integrate the complexity of nutrient exposure and biodisponibility associated with long-term risk of dementia in a large cohort of older persons, the Three-City study. METHODS: We included 666 nondemented participants with plasma measurements of 22 fat-soluble nutrients at baseline, who were followed up for 12 years for dementia. RESULTS: A "deleterious" pattern combining lower blood status in vitamin D, carotenoids, and polyunsaturated fats and higher saturated fats was strongly associated with a higher risk of dementia...
March 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28322204/cognitive-decline-associated-with-pathological-burden-in-primary-age-related-tauopathy
#6
Kyra S Jefferson-George, David A Wolk, Edward B Lee, Corey T McMillan
INTRODUCTION: Primary age-related tauopathy (PART) is a neuropathological diagnosis characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. Although most individuals over 50 years of age have evidence of NFTs, the clinical and cognitive consequences of PART are not known. METHODS: We evaluated 226 neuropathologically confirmed PART cases from the National Alzheimer's Coordinating Center database who participated in a total of 846 longitudinal neuropsychological assessments from the Alzheimer's Disease Center program's Uniform Data Set...
March 16, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28322203/associations-between-%C3%AE-amyloid-and-white-matter-hyperintensities-a-systematic-review
#7
REVIEW
Austyn Roseborough, Joel Ramirez, Sandra E Black, Jodi D Edwards
INTRODUCTION: This systematic review synthesizes current evidence for associations between cortical β-amyloid, visualized on amyloid positron emission tomography imaging, and white matter hyperintensity (WMH) burden on magnetic resonance imaging in healthy elderly adults and individuals with cognitive impairment and dementia. METHODS: Following PRISMA systematic review guidelines, we systematically searched MEDLINE, Embase, Cochrane, and PsycINFO databases from January 2000 to September 2015...
March 16, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28322202/genetic-epistasis-regulates-amyloid-deposition-in-resilient-aging
#8
Daniel Felsky, Jishu Xu, Lori Chibnik, Julie Schneider, Jo Knight, James L Kennedy, David A Bennett, Philip L De Jager, Aristotle N Voineskos
INTRODUCTION: The brain-derived neurotrophic factor (BDNF) interacts with important genetic Alzheimer's disease (AD) risk factors. Specifically, variants within the SORL1 gene determine BDNF's ability to reduce amyloid β (Aβ) in vitro. We sought to test whether functional BDNF variation interacts with SORL1 genotypes to influence expression and downstream AD-related processes in humans. METHODS: We analyzed postmortem brain RNA sequencing and neuropathological data for 441 subjects from the Religious Orders Study/Memory and Aging Project and molecular and structural neuroimaging data for 1285 subjects from the Alzheimer's Disease Neuroimaging Initiative...
March 16, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28314660/alzheimer-s-disease-the-next-frontier-special-report-2017
#9
Jason Karlawish, Clifford R Jack, Walter A Rocca, Heather M Snyder, Maria C Carrillo
In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging-Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis...
March 14, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28302453/brain-rhythm-attractor-breakdown-in-alzheimer-s-disease-functional-and-pathologic-implications
#10
Elissaios Karageorgiou, Keith A Vossel
This perspective binds emerging evidence on the bidirectional relationship between Alzheimer's disease (AD) and sleep disorders through a model of brain rhythm attractor breakdown. This approach explains behavioral-cognitive changes in AD across the sleep-wake cycle and supports a causal association between early brainstem tau pathology and subsequent cortical amyloid-β accumulation. Specifically, early tau dysregulation within brainstem-hypothalamic nuclei leads to breakdown of sleep-wake attractor networks, with patients displaying an attenuated range of behavioral and electrophysiological activity patterns, a "twilight zone" of constant activity between deep rest and full alertness...
March 13, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28274718/sugary-beverage-intake-and-preclinical-alzheimer-s-disease-in-the-community
#11
Matthew P Pase, Jayandra J Himali, Paul F Jacques, Charles DeCarli, Claudia L Satizabal, Hugo Aparicio, Ramachandran S Vasan, Alexa S Beiser, Sudha Seshadri
INTRODUCTION: Excess sugar consumption has been linked with Alzheimer's disease (AD) pathology in animal models. METHODS: We examined the cross-sectional association of sugary beverage consumption with neuropsychological (N = 4276) and magnetic resonance imaging (N = 3846) markers of preclinical Alzheimer's disease and vascular brain injury (VBI) in the community-based Framingham Heart Study. Intake of sugary beverages was estimated using a food frequency questionnaire...
March 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28264768/clinical-and-genetic-analyses-of-familial-and-sporadic-frontotemporal-dementia-patients-in-southern-italy
#12
Rosa Capozzo, Celeste Sassi, Monia B Hammer, Simona Arcuti, Chiara Zecca, Maria R Barulli, Rosanna Tortelli, J Raphael Gibbs, Cynthia Crews, Davide Seripa, Francesco Carnicella, Claudia Dell'Aquila, Marco Rossi, Filippo Tamma, Francesco Valluzzi, Bruno Brancasi, Francesco Panza, Andrew B Singleton, Giancarlo Logroscino
INTRODUCTION: We investigated the clinical differences between familial and sporadic frontotemporal dementia (FTD), screening for mutations in known FTD genes. METHODS: We diagnosed 22 affected individuals belonging to eight families and 43 sporadic cases with FTD in Apulia, Southern Italy, in 2 years. Mutations in common causative FTD genes (GRN, MAPT, VCP, and TARDBP) and C9ORF72 expansions were screened. RESULTS: Behavioral variant of FTD was the most common clinical subtype (50% and 69% in familial and sporadic cases, respectively)...
March 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28264767/spatial-navigation-and-risk-of-cognitive-impairment-a-prospective-cohort-study
#13
Joe Verghese, Richard Lipton, Emmeline Ayers
INTRODUCTION: Spatial navigation deficits are reported in dementia, but their temporal relationship to cognitive decline is not established. METHODS: This is a prospective cohort study in 442 nondemented adults (mean age 79.9 years). Spatial navigation measured with the Floor Maze Test and reported as immediate maze time (IMT) and delayed maze time (DMT). Predementia syndromes, mild cognitive impairment syndrome (MCI) and motoric cognitive risk syndrome (MCR), were primary outcomes...
March 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28263742/two-level-diagnostic-classification-using-cerebrospinal-fluid-ykl-40-in-alzheimer-s-disease
#14
Filippo Baldacci, Nicola Toschi, Simone Lista, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Roberto Floris, Francesco Garaci, Ubaldo Bonuccelli, Harald Hampel
INTRODUCTION: We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) YKL-40 in discriminating (1) clinical Alzheimer's disease (AD) from cognitively healthy controls (HCs) and frontotemporal dementia (FTD) (level I) and (2) patients stratified by different pathophysiological profiles from HCs and FTD following a novel unbiased/descriptive categorization based on CSF biomarkers, independent of cognitive impairment severity (level II). METHODS: YKL-40 was compared among HCs (n = 21), mild cognitive impairment (n = 41), AD (n = 35), and FTD (n = 9) (level I) and among HCs (n = 21), AD pathophysiology (tau and amyloid-β) negative (n = 15), tau positive (n = 15), amyloid-β positive (n = 13), AD pathophysiology positive (n = 33), and FTD (n = 9) (level II)...
March 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28263741/the-impact-of-automated-hippocampal-volumetry-on-diagnostic-confidence-in-patients-with-suspected-alzheimer-s-disease-an-eadc-study
#15
Paolo Bosco, Alberto Redolfi, Martina Bocchetta, Clarissa Ferrari, Anna Mega, Samantha Galluzzi, Mark Austin, Andrea Chincarini, D Louis Collins, Simon Duchesne, Bénédicte Maréchal, Alexis Roche, Francesco Sensi, Robin Wolz, Montserrat Alegret, Frederic Assal, Mircea Balasa, Christine Bastin, Anastasia Bougea, Derya Durusu Emek-Savaş, Sebastiaan Engelborghs, Timo Grimmer, Galina Grosu, Milica G Kramberger, Brian Lawlor, Gorana Mandic Stojmenovic, Mihaela Marinescu, Patrizia Mecocci, José Luis Molinuevo, Ricardo Morais, Ellis Niemantsverdriet, Flavio Nobili, Konstantinos Ntovas, Sarah O'Dwyer, George P Paraskevas, Luca Pelini, Agnese Picco, Eric Salmon, Isabel Santana, Oscar Sotolongo-Grau, Luiza Spiru, Elka Stefanova, Katarina Surlan Popovic, Magda Tsolaki, Görsev G Yener, Dina Zekry, Giovanni B Frisoni
INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge...
March 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28263740/safety-of-disclosing-amyloid-status-in-cognitively-normal-older-adults
#16
Jeffrey M Burns, David K Johnson, Edward P Liebmann, Rebecca J Bothwell, Jill K Morris, Eric D Vidoni
INTRODUCTION: Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. METHODS: We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. RESULTS: Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid)...
March 3, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28259709/consensus-classification-of-posterior-cortical-atrophy
#17
Sebastian J Crutch, Jonathan M Schott, Gil D Rabinovici, Melissa Murray, Julie S Snowden, Wiesje M van der Flier, Bradford C Dickerson, Rik Vandenberghe, Samrah Ahmed, Thomas H Bak, Bradley F Boeve, Christopher Butler, Stefano F Cappa, Mathieu Ceccaldi, Leonardo Cruz de Souza, Bruno Dubois, Olivier Felician, Douglas Galasko, Jonathan Graff-Radford, Neill R Graff-Radford, Patrick R Hof, Pierre Krolak-Salmon, Manja Lehmann, Eloi Magnin, Mario F Mendez, Peter J Nestor, Chiadi U Onyike, Victoria S Pelak, Yolande Pijnenburg, Silvia Primativo, Martin N Rossor, Natalie S Ryan, Philip Scheltens, Timothy J Shakespeare, Aida Suárez González, David F Tang-Wai, Keir X X Yong, Maria Carrillo, Nick C Fox
INTRODUCTION: A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. METHODS: Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA...
March 2, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28253478/early-and-late-change-on-the-preclinical-alzheimer-s-cognitive-composite-in-clinically-normal-older-individuals-with-elevated-amyloid-%C3%AE
#18
Elizabeth C Mormino, Kathryn V Papp, Dorene M Rentz, Michael C Donohue, Rebecca Amariglio, Yakeel T Quiroz, Jasmeer Chhatwal, Gad A Marshall, Nancy Donovan, Jonathan Jackson, Jennifer R Gatchel, Bernard J Hanseeuw, Aaron P Schultz, Paul S Aisen, Keith A Johnson, Reisa A Sperling
INTRODUCTION: Sensitive detection of cognitive decline over the course of preclinical Alzheimer's disease is critical as the field moves toward secondary prevention trials. METHODS: We examined amyloid-β (Aβ)-related change in several variations of the preclinical Alzheimer cognitive composite (PACC) and each individual PACC component in clinically normal (CN) older participants in the Harvard Aging Brain Study. We then examined the PACC variations in the Alzheimer's Disease Cooperative Study Prevention Instrument Study as a replication cohort...
February 28, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28242299/dysregulation-of-lipids-in-alzheimer-s-disease-and-their-role-as-potential-biomarkers
#19
REVIEW
Matthew W Wong, Nady Braidy, Anne Poljak, Russell Pickford, Madhav Thambisetty, Perminder S Sachdev
The brain is highly enriched in lipids, and an intensive study of these lipids may be informative, not only of normal brain function but also of changes with age and in disease. In recent years, the development of highly sensitive mass spectrometry platforms and other high-throughput technologies has enabled the discovery of complex changes in the entire lipidome. This lipidomics approach promises to be a particularly useful tool for identifying diagnostic biomarkers for early detection of age-related neurodegenerative disease, such as Alzheimer's disease (AD), which has till recently been limited to protein- and gene-centric approaches...
February 24, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28242298/the-alu-neurodegeneration-hypothesis-a-primate-specific-mechanism-for-neuronal-transcription-noise-mitochondrial-dysfunction-and%C3%A2-manifestation-of-neurodegenerative-disease
#20
Peter A Larsen, Michael W Lutz, Kelsie E Hunnicutt, Mirta Mihovilovic, Ann M Saunders, Anne D Yoder, Allen D Roses
It is hypothesized that retrotransposons have played a fundamental role in primate evolution and that enhanced neurologic retrotransposon activity in humans may underlie the origin of higher cognitive function. As a potential consequence of this enhanced activity, it is likely that neurons are susceptible to deleterious retrotransposon pathways that can disrupt mitochondrial function. An example is observed in the TOMM40 gene, encoding a β-barrel protein critical for mitochondrial preprotein transport. Primate-specific Alu retrotransposons have repeatedly inserted into TOMM40 introns, and at least one variant associated with late-onset Alzheimer's disease originated from an Alu insertion event...
February 24, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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