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

James D Stefaniak, Li Su, Elijah Mak, Nasim Sheikh Bahaei, Katie Wells, Karen Ritchie, Adam Waldman, Craig W Ritchie, John T O'Brien
INTRODUCTION: Cerebral small vessel disease (CSVD) is associated with late-onset Alzheimer's disease (LOAD) and might contribute to the relationship between apolipoprotein E ε4 (APOEε4) and LOAD, in older people. However, it is unclear whether CSVD begins in middle age in individuals genetically predisposed to LOAD. METHODS: We assessed the relationship between radiological markers of CSVD, white matter hyperintensities and microbleeds, and genetic predisposition to LOAD in a cross-sectional analysis of cognitively normal subjects aged 40-59 years recruited from the PREVENT Dementia study...
November 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Sonia Moreno-Grau, O Rodríguez-Gomez, A Sanabria, A Perez-Cordon, D Sanchez-Ruiz, C Abdelnour, S Valero, I Hernandez, M Rosende-Roca, A Mauleon, L Vargas, A Lafuente, S Gil, M A Santos-Santos, M Alegret, A Espinosa, G Ortega, M Guitart, A Gailhajanet, I de Rojas, O Sotolongo-Grau, S Ruiz, N Aguilera, J Papasey, E Martin, E Peleja, F Lomeña, F Campos, A Vivas, M Gomez-Chiari, M A Tejero, J Giménez, M Serrano-Ríos, A Orellana, L Tarraga, A Ruiz, M Boada
INTRODUCTION: Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. METHODS: We evaluated apolipoprotein E (APOE) Ɛ4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts...
November 17, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Eric D Vidoni, Rebecca J Bothwell, Jeffrey M Burns, John R Dwyer
No abstract text is available yet for this article.
November 17, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Peter D Fransquet, Paul Lacaze, Richard Saffery, John McNeil, Robyn Woods, Joanne Ryan
Dementia is a major public health issue with rising prevalence rates, but many individuals remain undiagnosed. Accurate and timely diagnosis is key for the optimal targeting of interventions. A noninvasive, easily measurable peripheral biomarker would have greatest utility in population-wide diagnostic screening. Epigenetics, including DNA methylation, is implicated in dementia; however, it is unclear whether epigenetic changes can be detected in peripheral tissue. This study aimed to systematically review the evidence for an association between dementia and peripheral DNA methylation...
November 8, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Mathieu Ceccaldi, Thérèse Jonveaux, Antoine Verger, Pierre Krolak-Salmon, Claire Houzard, Olivier Godefroy, Trevor Shields, Audrey Perrotin, Rossella Gismondi, Santiago Bullich, Aleksandar Jovalekic, Nicola Raffa, Florence Pasquier, Franck Semah, Bruno Dubois, Marie-Odile Habert, David Wallon, Mathieu Chastan, Pierre Payoux, Andrew Stephens, Eric Guedj
INTRODUCTION: Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting. METHODS: This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials...
November 4, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Noémie Letellier, Laure-Anne Gutierrez, Isabelle Carrière, Audrey Gabelle, Jean-François Dartigues, Carole Dufouil, Catherine Helmer, Emmanuelle Cadot, Claudine Berr
INTRODUCTION: The living environment affects general health and may influence cognitive aging; however, the relationships between neighborhood characteristics and dementia are still poorly understood. METHODS: We used data from a French population-based prospective study (the Three-City cohort) that included 7016 participants aged 65 years and older with a 12-year follow-up. We used principal components analysis of neighborhood composition indicators to construct the Three-City deprivation score...
November 1, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Tanis J Ferman, Naoya Aoki, Julia E Crook, Melissa E Murray, Neill R Graff-Radford, Jay A van Gerpen, Ryan J Uitti, Zbigniew K Wszolek, Jonathan Graff-Radford, Otto Pedraza, Kejal Kantarci, Bradley F Boeve, Dennis W Dickson
INTRODUCTION: We sought to assess the individual and combined contribution of limbic and neocortical α-synuclein, tau, and amyloid β (Aβ) to duration of illness in dementia with Lewy bodies (DLB). METHODS: Quantitative digital pathology of limbic and neocortical α-synuclein, tau, and Aβ was assessed in 49 patients with clinically probable DLB. Regression modeling examined the unique and shared contribution of each pathology to the variance of illness duration...
October 31, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Victor Montal, Eduard Vilaplana, Daniel Alcolea, Jordi Pegueroles, Ofer Pasternak, Sofia González-Ortiz, Jordi Clarimón, María Carmona-Iragui, Ignacio Illán-Gala, Estrella Morenas-Rodríguez, Roser Ribosa-Nogué, Isabel Sala, María-Belén Sánchez-Saudinós, Maite García-Sebastian, Jorge Villanúa, Andrea Izagirre, Ainara Estanga, Mirian Ecay-Torres, Ane Iriondo, Montserrat Clerigue, Mikel Tainta, Ana Pozueta, Andrea González, Eloy Martínez-Heras, Sara Llufriu, Rafael Blesa, Pascual Sanchez-Juan, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea
INTRODUCTION: Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD). METHODS: We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9)...
October 31, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Serge Gauthier, Julie Robillard, Johane de Champlain
No abstract text is available yet for this article.
October 28, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Mariet Allen, Xue Wang, Jeremy D Burgess, Jens Watzlawik, Daniel J Serie, Curtis S Younkin, Thuy Nguyen, Kimberly G Malphrus, Sarah Lincoln, Minerva M Carrasquillo, Charlotte Ho, Paramita Chakrabarty, Samantha Strickland, Melissa E Murray, Vivek Swarup, Daniel H Geschwind, Nicholas T Seyfried, Eric B Dammer, James J Lah, Allan I Levey, Todd E Golde, Cory Funk, Hongdong Li, Nathan D Price, Ronald C Petersen, Neill R Graff-Radford, Steven G Younkin, Dennis W Dickson, Julia R Crook, Yan W Asmann, Nilüfer Ertekin-Taner
INTRODUCTION: Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways. METHODS: We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects. RESULTS: We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD...
October 26, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Adriana Seelye, Nora Mattek, Nicole Sharma, Thomas Riley, Johanna Austin, Katherine Wild, Hiroko H Dodge, Emily Lore, Jeffrey Kaye
INTRODUCTION: Subtle changes in instrumental activities of daily living often accompany the onset of mild cognitive impairment (MCI) but are difficult to measure using conventional tests. METHODS: Weekly online survey metadata metrics, annual neuropsychological tests, and an instrumental activity of daily living questionnaire were examined in 110 healthy older adults with intact cognition (mean age = 85 years) followed up for up to 3.6 years; 29 transitioned to MCI during study follow-up...
October 26, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Paul K Crane, Tatiana Foroud, Thomas J Montine, Eric B Larson
INTRODUCTION: The Alzheimer's Disease Sequencing Project (ADSP) used different criteria for assigning case and control status from the discovery and replication phases of the project. We considered data from a community-based prospective cohort study with autopsy follow-up where participants could be categorized as case, control, or neither by both definitions and compared the two sets of criteria. METHODS: We used data from the Adult Changes in Thought (ACT) study including Diagnostic and Statistical Manual-IV criteria for dementia status, McKhann et al...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Yang An, Vijay R Varma, Sudhir Varma, Ramon Casanova, Eric Dammer, Olga Pletnikova, Chee W Chia, Josephine M Egan, Luigi Ferrucci, Juan Troncoso, Allan I Levey, James Lah, Nicholas T Seyfried, Cristina Legido-Quigley, Richard O'Brien, Madhav Thambisetty
INTRODUCTION: It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. METHODS: Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Anna Rosenberg, Tiia Ngandu, Minna Rusanen, Riitta Antikainen, Lars Bäckman, Satu Havulinna, Tuomo Hänninen, Tiina Laatikainen, Jenni Lehtisalo, Esko Levälahti, Jaana Lindström, Teemu Paajanen, Markku Peltonen, Hilkka Soininen, Anna Stigsdotter-Neely, Timo Strandberg, Jaakko Tuomilehto, Alina Solomon, Miia Kivipelto
INTRODUCTION: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition. METHODS: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia)...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Katherine J Sellers, Christina Elliott, Joshua Jackson, Anshua Ghosh, Elena Ribe, Ana I Rojo, Heledd H Jarosz-Griffiths, Iain A Watson, Weiming Xia, Mikhail Semenov, Peter Morin, Nigel M Hooper, Rod Porter, Jane Preston, Raya Al-Shawi, George Baillie, Simon Lovestone, Antonio Cuadrado, Michael Harte, Paul Simons, Deepak P Srivastava, Richard Killick
INTRODUCTION: Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death. METHODS: We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Olivia A Skrobot, Sandra E Black, Christopher Chen, Charles DeCarli, Timo Erkinjuntti, Gary A Ford, Rajesh N Kalaria, John O'Brien, Leonardo Pantoni, Florence Pasquier, Gustavo C Roman, Anders Wallin, Perminder Sachdev, Ingmar Skoog, Yoav Ben-Shlomo, Anthony P Passmore, Seth Love, Patrick G Kehoe
INTRODUCTION: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. METHODS: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI...
October 19, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Isaac Acosta, Guilherme Borges, Rebeca Aguirre-Hernandez, Ana Luisa Sosa, Martin Prince
INTRODUCTION: Cognitive and/or memory impairment are the main clinical markers currently used to identify subjects at risk of developing dementia. This study aimed to explore the relationship between the presence of neuropsychiatric symptoms and dementia incidence. METHODS: We analyzed the association between neuropsychiatric symptoms and incident dementia in a cohort of 1355 Mexican older adults from the general population over 3 years of follow-up, modeling cumulative incidence ratios using Poisson models...
October 10, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Harald Hampel, Marsel M Mesulam, A Claudio Cuello, Ara S Khachaturian, Martin R Farlow, Peter J Snyder, Ezio Giacobini, Zaven S Khachaturian
Scientific evidence collected over the past four decades suggests that a loss of cholinergic innervation in the cerebral cortex of patients with Alzheimer's disease (AD) is an early pathogenic event correlated with cognitive impairment. This evidence led to the formulation of the "cholinergic hypothesis of AD" and the development of cholinesterase inhibitor therapies. Although approved only as symptomatic therapies, recent studies suggest that long-term use of these drugs may also have disease-modifying benefits...
October 10, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Mahmoud Reza Azarpazhooh, Abolfazl Avan, Lauren E Cipriano, David G Munoz, Luciano A Sposato, Vladimir Hachinski
INTRODUCTION: The relative contributions of vascular and degenerative pathology to dementia are unknown. We aim to quantify the proportion of dementia explained by potentially preventable vascular lesions. METHODS: We systematically searched for population-based cohorts before February 2017 reporting clinicopathological data for individuals with and without dementia. We calculated the summary proportion and absolute risk of dementia comparing subjects with and without the pathology...
September 30, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Danièlle Gunn-Moore, Oksana Kaidanovich-Beilin, María Carolina Gallego Iradi, Frank Gunn-Moore, Simon Lovestone
INTRODUCTION: Alzheimer's disease and diabetes mellitus are linked by epidemiology, genetics, and molecular pathogenesis. They may also be linked by the remarkable observation that insulin signaling sets the limits on longevity. In worms, flies, and mice, disrupting insulin signaling increases life span leading to speculation that caloric restriction might extend life span in man. It is our contention that man is already a long-lived organism, specifically with a remarkably high postfertility life span, and that it is this that results in the prevalence of Alzheimer's disease and diabetes...
September 30, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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