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

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https://www.readbyqxmd.com/read/28431219/genetic-analysis-of-%C3%AE-synuclein-3-untranslated-region-and-its-corresponding-micrornas-in-relation-to-parkinson-s-compared-to-dementia-with-lewy-bodies
#1
Lidia Tagliafierro, Omolara-Chinue Glenn, Madison E Zamora, Thomas G Beach, Randy L Woltjer, Michael W Lutz, Ornit Chiba-Falek
INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time PCR to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants...
April 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28431218/response-to-letter-to-the-editor
#2
LETTER
Maria C Carrillo, Howard Fillit, Mary Ganguli, David Knoman, Diana Shineman, Heather M Snyder
No abstract text is available yet for this article.
April 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28427934/cognitive-subtypes-of-probable-alzheimer-s-disease-robustly-identified-in%C3%A2-four-cohorts
#3
Nienke M E Scheltens, Betty M Tijms, Teddy Koene, Frederik Barkhof, Charlotte E Teunissen, Steffen Wolfsgruber, Michael Wagner, Johannes Kornhuber, Oliver Peters, Brendan I Cohn-Sheehy, Gil D Rabinovici, Bruce L Miller, Joel H Kramer, Philip Scheltens, Wiesje M van der Flier
INTRODUCTION: Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach. METHODS: We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589)...
April 17, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28366797/tau-and-amyloid-%C3%AE-proteins-distinctively-associate-to-functional-network-changes-in-the-aging-brain
#4
Jorge Sepulcre, Mert R Sabuncu, Quanzheng Li, Georges El Fakhri, Reisa Sperling, Keith A Johnson
INTRODUCTION: Misfolded tau and amyloid β (Aβ) proteins progressively accumulate in the human brain, causing altered neuronal function and neurodegeneration. This study sought to investigate whether the wide spectrum of functional reorganization in aging brains of cognitively normal individuals relates to specific pathological patterns of tau and Aβ deposits. METHODS: We used functional connectivity neuroimaging and in vivo tau and Aβ positron emission tomography scans to study cortical spatial relationships between imaging modalities...
March 30, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28365321/the-midlife-cognitive-profiles-of-adults-at-high-risk-of-late-onset-alzheimer-s-disease-the-prevent-study
#5
Karen Ritchie, Isabelle Carrière, Li Su, John T O'Brien, Simon Lovestone, Katie Wells, Craig W Ritchie
INTRODUCTION: Although biomarker studies of late-onset Alzheimer's disease suggest pathology to be present decades before diagnosis, little is known about cognitive performance at this stage. METHODS: A sample of 210 adults (aged 40-59) of whom 103 have a parent diagnosed with dementia (family history subgroup) underwent computerized cognitive testing. Apolipoprotein E (apoE) status was determined, and 193 subjects had magnetic resonance imaging. Distance from dementia onset was estimated in relation to age of parental diagnosis, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Scores were calculated...
March 30, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28365320/use-of-white-matter-reference-regions-for-detection-of-change-in-florbetapir-positron-emission-tomography-from-completed-phase-3-solanezumab-trials
#6
Adam S Fleisher, Abhinay D Joshi, Karen L Sundell, Yun-Fei Chen, Sara Kollack-Walker, Ming Lu, Sherry Chen, Michael D Devous, John Seibyl, Kenneth Marek, Eric R Siemers, Mark A Mintun
INTRODUCTION: We compared subject-specific white matter (SSWM) and whole cerebellum (CBL) reference regions for power to detect longitudinal change in amyloid positron emission tomography signal. METHODS: Positive florbetapir positron emission tomography scans were analyzed from participants (66 placebo treated and 63 solanezumab treated) with mild dementia caused by Alzheimer's disease from the EXPEDITION and EXPEDITION2 studies. For comparison to CBL, a second normalization was performed on longitudinal data using an SSWM correction factor (SSWM normalization ratio [SSWMnr])...
March 30, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28363085/population-based-stroke-and-dementia-incidence-trends-age-and-sex-variations
#7
Joshua O Cerasuolo, Lauren E Cipriano, Luciano A Sposato, Moira K Kapral, Jiming Fang, Sudeep S Gill, Daniel G Hackam, Vladimir Hachinski
INTRODUCTION: We discovered a concomitant decline in stroke and dementia incidence rates at a whole population level in Ontario, Canada. This study explores these trends within demographic subgroups. METHODS: We analyzed administrative data sources using validated algorithms to calculate stroke and dementia incidence rates from 2002 to 2013. RESULTS: For more than 12 years, stroke incidence remained unchanged among those aged 20 to 49 years and decreased for those aged 50 to 64, 65 to 79, and 80+ years by 22...
March 28, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28343848/capillary-dysfunction-is-associated-with-symptom-severity-and-neurodegeneration-in-alzheimer-s-disease
#8
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
#9
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
#10
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) subscale 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
#11
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
#12
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/28322202/genetic-epistasis-regulates-amyloid-deposition-in-resilient-aging
#13
Daniel Felsky, Jishu Xu, Lori B Chibnik, Julie A 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 17, 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
#14
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-amyloid-%C3%AE-and-white-matter-hyperintensities-a-systematic-review
#15
REVIEW
Austyn Roseborough, Joel Ramirez, Sandra E Black, Jodi D Edwards
INTRODUCTION: This systematic review synthesizes current evidence for associations between cortical amyloid β, 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 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (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/28314660/alzheimer-s-disease-the-next-frontier-special-report-2017
#16
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
#17
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 14, 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
#18
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
#19
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
#20
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
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