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

Juliane Schelle, Lisa Häsler, Jens C Göpfert, Thomas O Joos, Hugo Vanderstichele, Erik Stoops, Ulf Neumann, Derya R Shimshek, Matthias Staufenbiel, Mathias Jucker, Stephan A Kaeser
INTRODUCTION: The inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of Aβ precursor protein (APP) transgenic mice. METHODS: APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high-sensitivity tau sandwich immunoassay was developed...
October 14, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Benjamin Lam, Aun Khan, Julia Keith, Ekaterina Rogaeva, Juan Bilbao, Peter St George-Hyslop, Mahdi Ghani, Morris Freedman, Donald T Stuss, Tiffany Chow, Sandra E Black, Mario Masellis
INTRODUCTION: Corticobasal syndrome (CBS) resulting from genetic Alzheimer's disease (AD) has been described only once. Whether familial CBS-AD is a distinct clinical entity with its own imaging signature remains unknown. METHODS: Four individuals with CBS from two families underwent detailed assessment. For two individuals, regional atrophy and hypoperfusion were compared to autopsy-confirmed typical late-onset AD and corticobasal degeneration, as well as genetically proven PSEN1 cases with an amnestic presentation...
October 12, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Karen Ritchie, Michael Ropacki, B Albala, John Harrison, Jeffrey Kaye, Joel Kramer, Christopher Randolph, C W Ritchie
The Horizon 2020/IMI European Prevention of Alzheimer's Dementia (EPAD) project will undertake large-scale proof-of-concept trials in predementia AD. Within EPAD, the monitoring of cognitive trajectories in the preclinical period will constitute a central outcome measure; however, there are currently no clear guidelines as to how this should be achieved as most measures have been developed for the period around dementia diagnosis. The EPAD Scientific Advisory Group for Clinical and Cognitive Outcomes identified appropriate cognitive measures based on a literature search covering both cognitive correlates of preclinical brain changes from imaging studies and cognitive changes observed over time in nondementia population cohorts developing incident dementia...
October 1, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
M Mortamais, J A Ash, J Harrison, J Kaye, J Kramer, C Randolph, C Pose, B Albala, M Ropacki, C W Ritchie, K Ritchie
Significant progress has been made in characterizing the biological changes occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been viewed, however, as a late-stage phenomenon, despite increasing evidence that changes may be detected in the decades preceding dementia. In the absence of comprehensive evidence-based guidelines for preclinical cognitive assessment, longitudinal cohort and neuroimaging studies have been reviewed to determine the temporal order and brain biomarker correlates of specific cognitive functions...
October 1, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Clifford R Jack, Heather J Wiste, Stephen D Weigand, Terry M Therneau, Val J Lowe, David S Knopman, Jeffrey L Gunter, Matthew L Senjem, David T Jones, Kejal Kantarci, Mary M Machulda, Michelle M Mielke, Rosebud O Roberts, Prashanthi Vemuri, Denise Reyes, Ronald C Petersen
INTRODUCTION: Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness. METHODS: We examined five methods for determining cut points. RESULTS: The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of clinically impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness...
September 30, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Andrés Norambuena, Horst Wallrabe, Lloyd McMahon, Antonia Silva, Eric Swanson, Shahzad S Khan, Daniel Baerthlein, Erin Kodis, Salvatore Oddo, James W Mandell, George S Bloom
A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles...
September 29, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jordi Pegueroles, Eduard Vilaplana, Victor Montal, Frederic Sampedro, Daniel Alcolea, Maria Carmona-Iragui, Jordi Clarimon, Rafael Blesa, Alberto Lleó, Juan Fortea
BACKGROUND: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood. METHODS: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates. RESULTS: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Thomas Leyhe, Charles F Reynolds, Tobias Melcher, Christoph Linnemann, Stefan Klöppel, Kaj Blennow, Henrik Zetterberg, Bruno Dubois, Simone Lista, Harald Hampel
Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Audrey Perrotin, Renaud La Joie, Vincent de La Sayette, Louisa Barré, Florence Mézenge, Justine Mutlu, Denis Guilloteau, Stéphanie Egret, Francis Eustache, Gaël Chételat
INTRODUCTION: Subjective cognitive decline (SCD) could indicate preclinical Alzheimer's disease, but the existing literature is confounded by heterogeneous approaches to studying SCD. We assessed the differential cognitive, affective, and neuroimaging correlates of two aspects of SCD: reporting high cognitive difficulties on a self-rated questionnaire versus consulting at a memory clinic. METHODS: We compared 28 patients from a memory clinic with isolated SCD, 35 community-recruited elders with similarly high levels of self-reported cognitive difficulties, and 35 community-recruited controls with low self-reported cognitive difficulties...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Thanh G N Ton, Thomas DeLeire, Suepattra G May, Ningqi Hou, Mahlet G Tebeka, Er Chen, Joshua Chodosh
INTRODUCTION: Individuals with amnestic mild cognitive impairment (aMCI) are at elevated risk of developing Alzheimer's disease (AD) dementia. METHODS: With data from the Aging, Demographics, and Memory Study, we used the Clinical Dementia Rating Sum of Boxes classifications to conduct a cross-sectional analysis assessing the relationship between cognitive state and various direct and indirect costs and health care utilization patterns. RESULTS: Patients with aMCI had less medical expenditures than patients with moderate and severe AD dementia (P < ...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Francisca S Then, Tobias Luck, Kathrin Heser, Annette Ernst, Tina Posselt, Birgitt Wiese, Silke Mamone, Christian Brettschneider, Hans-Helmut König, Siegfried Weyerer, Jochen Werle, Edelgard Mösch, Horst Bickel, Angela Fuchs, Michael Pentzek, Wolfgang Maier, Martin Scherer, Michael Wagner, Steffi G Riedel-Heller
INTRODUCTION: Previous studies have demonstrated that an overall high level of mental work demands decreased dementia risk. In our study, we investigated whether this effect is driven by specific mental work demands and whether it is exposure dependent. METHODS: Patients aged 75+ years were recruited from general practitioners and participated in up to seven assessment waves (every 1.5 years) of the longitudinal AgeCoDe study. Analyses of the impact of specific mental work demands on dementia risk were carried out via multivariate regression modeling (n = 2315)...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Petroula Proitsi, Min Kim, Luke Whiley, Andrew Simmons, Martina Sattlecker, Latha Velayudhan, Michelle K Lupton, Hillka Soininen, Iwona Kloszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Simon Lovestone, John F Powell, Richard J B Dobson, Cristina Legido-Quigley
INTRODUCTION: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex). METHODS: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Hugo Lövheim, Fredrik Elgh, Anders Johansson, Henrik Zetterberg, Kaj Blennow, Göran Hallmans, Sture Eriksson
INTRODUCTION: Biomarkers that identify individuals at risk of Alzheimer's disease (AD) development would be highly valuable. Plasma concentration of amyloid-β (Aβ)-central in the pathogenesis of AD-is a logical candidate, but studies to date have produced conflicting results on its utility. METHODS: Plasma samples from 339 preclinical AD cases (76.4% women, mean age 61.3 years) and 339 age- and sex-matched dementia-free controls, taken an average of 9.4 years before AD diagnosis, were analyzed using Luminex xMAP technology and INNOBIA plasma Aβ form assays to determine concentrations of free plasma Aβ40 and Aβ42...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ruiqing Ni, Per-Göran Gillberg, Nenad Bogdanovic, Matti Viitanen, Liisa Myllykangas, Inger Nennesmo, Bengt Långström, Agneta Nordberg
INTRODUCTION: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structure and amyloid-β aggregate in autosomal dominant AD (ADAD) and sporadic AD is unclear. METHODS: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases. RESULTS: (3)H-PIB, (3)H-florbetaben, (3)H-AZD2184, and BTA-1 shared a high- and a varying low-affinity binding site in the frontal cortex of sporadic AD...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Anna E Leeuwis, Marije R Benedictus, Joost P A Kuijer, Maja A A Binnewijzend, Astrid M Hooghiemstra, Sander C J Verfaillie, Teddy Koene, Philip Scheltens, Frederik Barkhof, Niels D Prins, Wiesje M van der Flier
INTRODUCTION: We examined the association between decreased cerebral blood flow (CBF) and cognitive impairment in Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD). METHODS: We included 161 AD, 95 MCI, and 143 SCD patients from the Amsterdam Dementia Cohort. We used 3-T pseudo-continuous arterial spin labeling to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and five cognitive domains...
September 28, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Heather M Snyder, Sanjay Asthana, Lisa Bain, Roberta Brinton, Suzanne Craft, Dena B Dubal, Mark A Espeland, Margaret Gatz, Michelle M Mielke, Jacob Raber, Peter R Rapp, Kristine Yaffe, Maria C Carrillo
More than 5 million Americans are living with Alzheimer's disease (AD) today, and nearly two-thirds of Americans with AD are women. This sex difference may be due to the higher longevity women generally experience; however, increasing evidence suggests that longevity alone is not a sufficient explanation and there may be other factors at play. The Alzheimer's Association convened an expert think tank to focus on the state of the science and level of evidence around gender and biological sex differences for AD, including the knowledge gaps and areas of science that need to be more fully addressed...
September 21, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
John G Geisler, Krisztina Marosi, Joshua Halpern, Mark P Mattson
Recent findings have elucidated roles for mitochondrial uncoupling proteins (UCPs) in neuronal plasticity and resistance to metabolic and oxidative stress. UCPs are induced by bioenergetic challenges such as caloric restriction and exercise and may protect neurons against dysfunction and degeneration. The pharmacological uncoupler 2,4-dinitrophenol (DNP), which was once prescribed to >100,000 people as a treatment for obesity, stimulates several adaptive cellular stress-response signaling pathways in neurons including those involving the brain-derived neurotrophic factor (BDNF), the transcription factor cyclic AMP response element-binding protein (CREB), and autophagy...
September 4, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Vanesa Bellou, Lazaros Belbasis, Ioanna Tzoulaki, Lefkos T Middleton, John P A Ioannidis, Evangelos Evangelou
INTRODUCTION: Dementia is a heterogeneous neurodegenerative disease, whose etiology results from a complex interplay between environmental and genetic factors. METHODS: We searched PubMed to identify meta-analyses of observational studies that examined associations between nongenetic factors and dementia. We estimated the summary effect size using random-effects and fixed-effects model, the 95% CI, and the 95% prediction interval. We assessed the between-study heterogeneity (I-square), evidence of small-study effects, and excess significance...
September 4, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Kala M Mehta, Gwen W Yeo
OBJECTIVE: To identify incidence and prevalence of dementia in racial and ethnic populations in the United States. METHODS: A systematic review of literature. RESULTS: A total of 1215 studies were reviewed; 114 were included. Dementia prevalence rates reported for age 65+ years from a low of 6.3% in Japanese Americans, 12.9% in Caribbean Hispanic Americans, 12.2% in Guamanian Chamorro and ranged widely in African Americans from 7.2% to 20...
September 3, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Yingjia Chen, Katherine G Denny, Danielle Harvey, Sarah Tomaszewski Farias, Dan Mungas, Charles DeCarli, Laurel Beckett
IMPORTANCE: Investigation of the conversion rates from normal cognition (NC) to mild cognitive impairment (MCI) is important, as effective early intervention could potentially prevent or substantially delay the onset of dementia. However, reported conversion rates differ across studies and recruitment source. OBJECTIVE: Our study examined predictors of conversion from NC to MCI in a racially and ethnically diverse sample drawn both from community and clinic recruitment sources...
August 30, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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