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

Jessica Tulloch, Lesley Leong, Sunny Chen, C Dirk Keene, Steven P Millard, Andrew Shutes-David, Oscar L Lopez, Julia Kofler, Jeffrey A Kaye, Randy Woltjer, Peter T Nelson, Janna H Neltner, Gregory A Jicha, Douglas Galasko, Eliezer Masliah, James B Leverenz, Chang-En Yu, Debby Tsuang
INTRODUCTION: Inheritance of the ε4 allele of apolipoprotein E (APOE) increases a person's risk of developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced APOE DNA methylation in AD postmortem brains prompted this study to investigate APOE methylation in LBD. METHODS: Genomic DNA from postmortem brain tissues (frontal lobe and cerebellum) of neuropathological pure (np) controls and npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced...
March 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ornit Chiba-Falek, William K Gottschalk, Michael W Lutz
The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in linkage disequilibrium with APOE. Roses et al identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzheimer's disease (LOAD). Following the original discovery, additional studies found associations between the TOMM40 poly-T and LOAD-related phenotypes independent of APOE genotypes, while others did not replicate these associations. Furthermore, the identity of the TOMM40 poly-T risk allele has been controversial between different LOAD-related phenotypes...
March 7, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Frank J Wolters, Reffat A Segufa, Sirwan K L Darweesh, Daniel Bos, Mohammad Arfan Ikram, Behnam Sabayan, Albert Hofman, Sanaz Sedaghat
INTRODUCTION: Cardiovascular risk factors are closely linked with dementia risk, but whether heart disease predisposes to dementia is uncertain. METHODS: We systematically reviewed the literature and meta-analyzed risk estimates from longitudinal studies reporting the association of coronary heart disease (CHD) or heart failure (HF) with risk of dementia. RESULTS: We identified 16 studies (1,309,483 individuals) regarding CHD, and seven studies (1,958,702 individuals) about HF...
March 2, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jeremy M Silverman, James Schmeidler
INTRODUCTION: Some associations of high total cholesterol with dementia risk diminish as the outcome age-age at cognitive assessment-increases. METHODS: The Framingham Heart Study provided 1897 participants with intact cognition at entry. Cox regression analysis for incident marked cognitive decline included "time-dependent" coefficients, with associations between total cholesterol and covariates changing by outcome age. Decline within age categories of 75-84 and 85-94 years was also examined...
March 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Suzanne E Schindler, Julia D Gray, Brian A Gordon, Chengjie Xiong, Richard Batrla-Utermann, Marian Quan, Simone Wahl, Tammie L S Benzinger, David M Holtzman, John C Morris, Anne M Fagan
INTRODUCTION: Levels of amyloid β peptide 42 (Aβ42), total tau, and phosphorylated tau-181 are well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, but variability in manual plate-based assays has limited their use. We examined the relationship between CSF biomarkers, as measured by a novel automated immunoassay platform, and amyloid positron emission tomography. METHODS: CSF samples from 200 individuals underwent separate analysis for Aβ42, total tau, and phosphorylated tau-181 with the automated Roche Elecsys cobas e 601 analyzer...
March 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Juho Tynkkynen, Vincent Chouraki, Sven J van der Lee, Jussi Hernesniemi, Qiong Yang, Shuo Li, Alexa Beiser, Martin G Larson, Katri Sääksjärvi, Martin J Shipley, Archana Singh-Manoux, Robert E Gerszten, Thomas J Wang, Aki S Havulinna, Peter Würtz, Krista Fischer, Ayse Demirkan, M Arfan Ikram, Najaf Amin, Terho Lehtimäki, Mika Kähönen, Markus Perola, Andres Metspalu, Antti J Kangas, Pasi Soininen, Mika Ala-Korpela, Ramachandran S Vasan, Mika Kivimäki, Cornelia M van Duijn, Sudha Seshadri, Veikko Salomaa
INTRODUCTION: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. METHODS: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented...
February 28, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Oskar Hansson, John Seibyl, Erik Stomrud, Henrik Zetterberg, John Q Trojanowski, Tobias Bittner, Valeria Lifke, Veronika Corradini, Udo Eichenlaub, Richard Batrla, Katharina Buck, Katharina Zink, Christina Rabe, Kaj Blennow, Leslie M Shaw
INTRODUCTION: We studied whether fully automated Elecsys cerebrospinal fluid (CSF) immunoassay results were concordant with PET and predicted clinical progression, even with cutoffs established in an independent cohort. METHODS: Cutoffs for Elecsys amyloid-β1-42 (Aβ), total tau/Aβ(1-42), and phosphorylated tau/Aβ(1-42) were defined against [18 F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18 F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646)...
February 27, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Shahzad Ahmad, Christian Bannister, Sven J van der Lee, Dina Vojinovic, Hieab H H Adams, Alfredo Ramirez, Valentina Escott-Price, Rebecca Sims, Emily Baker, Julie Williams, Peter Holmans, Meike W Vernooij, M Arfan Ikram, Najaf Amin, Cornelia M van Duijn
INTRODUCTION: Exploring the role of Alzheimer's disease (AD) implicated pathways in the predementia phase may provide new insight for preventive and clinical trials targeting disease specific pathways. METHODS: We constructed weighted Genetic risk scores, first based on 20 genome-wide significant AD risk variants and second clustering these variants within pathways. Risk scores were investigated for their association with AD, mild cognitive impairment, and brain magnetic resonance imaging phenotypes including white matter lesions, hippocampal volume, and brain volume...
February 26, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Joseph Rogers
INTRODUCTION: Neuroinflammation is now considered to be of pathophysiologic significance in Alzheimer's disease and other neurodegenerative conditions. Nonetheless, there is no consensus as to what inflammatory mechanisms need to be combated (or facilitated), how therapies for them should be applied, or when they might be efficacious. METHODS: This article seeks to put forward cornerstone facts about neuroinflammation, with suggestions for future directions. RESULTS: Multiple scientific points about neuroinflammation still remain unaddressed...
February 26, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Saak V Ovsepian, Valerie B O'Leary, Laszlo Zaborszky, Vasilis Ntziachristos, Oliver J Dolly
The synaptic vesicle cycle (SVC) holds center stage in the biology of presynaptic terminals. Through recurrent exocytosis and endocytosis, it facilitates a sequence of events enabling chemical neurotransmission between functionally related neurons. As a fundamental process that links the interior of nerve cells with their environment, the SVC is also critical for signaling and provides an entry route for a range of pathogens and toxins, enabling detrimental effects. In Alzheimer's disease, the SVC is both the prime site of amyloid β production and toxicity...
February 26, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ann D Cohen, Eric McDade, Brad Christian, Julie Price, Chester Mathis, William Klunk, Benjamin L Handen
INTRODUCTION: The objective of this study was to evaluate amyloid β (Aβ) deposition patterns in different groups of cerebral β amyloidosis: (1) nondemented with amyloid precursor protein overproduction (Down syndrome); (2) nondemented with abnormal processing of amyloid precursor protein (preclinical autosomal dominant Alzheimer disease); (3) presumed alteration in Aβ clearance with clinical symptoms (late-onset AD); and (4) presumed alterations in Aβ clearance (preclinical AD). METHODS: We performed whole-brain voxelwise comparison of cerebral Aβ between 23 Down syndrome, 10 preclinical autosomal dominant Alzheimer disease, 17 late-onset AD, and 16 preclinical AD subjects, using PiB-PET...
February 22, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Olivier Hanon, Jean-Sébastien Vidal, Sylvain Lehmann, Stéphanie Bombois, Bernadette Allinquant, Jean-Marc Tréluyer, Patrick Gelé, Christine Delmaire, Fredéric Blanc, Jean-François Mangin, Luc Buée, Jacques Touchon, Jacques Hugon, Bruno Vellas, Evelyne Galbrun, Athanase Benetos, Gilles Berrut, Elèna Paillaud, David Wallon, Giovanni Castelnovo, Lisette Volpe-Gillot, Marc Paccalin, Philippe-Henri Robert, Olivier Godefroy, Thierry Dantoine, Vincent Camus, Joël Belmin, Pierre Vandel, Jean-Luc Novella, Emmanuelle Duron, Anne-Sophie Rigaud, Suzanna Schraen-Maschke, Audrey Gabelle
BACKGROUNDS: Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. OBJECTIVES: To assess plasma levels of Aβ42 and Aβ40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. METHODS: One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included...
February 16, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Marco Duering, Sofia Finsterwalder, Ebru Baykara, Anil Man Tuladhar, Benno Gesierich, Marek J Konieczny, Rainer Malik, Nicolai Franzmeier, Michael Ewers, Eric Jouvent, Geert Jan Biessels, Reinhold Schmidt, Frank-Erik de Leeuw, Ofer Pasternak, Martin Dichgans
INTRODUCTION: Diffusion tensor imaging detects early tissue alterations in Alzheimer's disease and cerebral small vessel disease (SVD). However, the origin of diffusion alterations in SVD is largely unknown. METHODS: To gain further insight, we applied free water (FW) imaging to patients with genetically defined SVD (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, n = 57), sporadic SVD (n = 444), and healthy controls (n = 28)...
February 1, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Jaimie C Hunter, Elizabeth P Handing, Ramon Casanova, Maragatha Kuchibhatla, Michael W Lutz, Santiago Saldana, Brenda L Plassman, Kathleen M Hayden
INTRODUCTION: We evaluated the association between neighborhood socioeconomic status (NSES) and sleep quality on cognitive decline in the Health and Retirement Study. METHODS: Health and Retirement Study participants (n = 8090), aged 65+ with DNA and multiple biennial cognitive observations (abbreviated Telephone Interview for Cognitive Status), were included. Participants were grouped into quartiles of NSES and sleep quality scores. We adjusted for apolipoprotein E ε4, demographic, and cardiovascular risk factors...
January 30, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Inga Zerr, Matthias Schmitz, André Karch, Anna Villar-Piqué, Eirini Kanata, Ewa Golanska, Daniela Díaz-Lucena, Aikaterini Karsanidou, Peter Hermann, Tobias Knipper, Stefan Goebel, Daniela Varges, Theodoros Sklaviadis, Beata Sikorska, Pawel P Liberski, Isabel Santana, Isidro Ferrer, Henrik Zetterberg, Kaj Blennow, Olga Calero, Miguel Calero, Anna Ladogana, Raquel Sánchez-Valle, Inês Baldeiras, Franc Llorens
INTRODUCTION: Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown. METHODS: Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182)...
January 29, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Annie Robitaille, Ardo van den Hout, Robson J M Machado, David A Bennett, Iva Čukić, Ian J Deary, Scott M Hofer, Emiel O Hoogendijk, Martijn Huisman, Boo Johansson, Andriy V Koval, Maaike van der Noordt, Andrea M Piccinin, Judith J M Rijnhart, Archana Singh-Manoux, Johan Skoog, Ingmar Skoog, John Starr, Lisa Vermunt, Sean Clouston, Graciela Muniz Terrera
INTRODUCTION: This study examines the role of educational attainment, an indicator of cognitive reserve, on transitions in later life between cognitive states (normal Mini-Mental State Examination (MMSE), mild MMSE impairment, and severe MMSE impairment) and death. METHODS: Analysis of six international longitudinal studies was performed using a coordinated approach. Multistate survival models were used to estimate the transition patterns via different cognitive states...
January 25, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Diego Mastroeni, Jennifer Nolz, Omar M Khdour, Shobana Sekar, Elaine Delvaux, Lori Cuyugan, Winnie S Liang, Sidney M Hecht, Paul D Coleman
INTRODUCTION: Our laboratories have demonstrated that accumulation of oligomeric amyloid β (OAβ) in neurons is an essential step leading to OAβ-mediated mitochondrial dysfunction. METHODS: Alzheimer's disease (AD) and matching control hippocampal neurons, astrocytes, and microglia were isolated by laser-captured microdissection from the same subjects, followed by whole-transcriptome sequencing. Complementary in vitro work was performed in OAβ-treated differentiated SH-SY5Y, followed by the use of a novel CoQ10 analogue for protection...
January 20, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Justin Miron, Cynthia Picard, Nathalie Nilsson, Josée Frappier, Doris Dea, Louise Théroux, Judes Poirier
INTRODUCTION: Because currently known Alzheimer's disease (AD) single-nucleotide polymorphisms only account for a small fraction of the genetic variance in this disease, there is a need to identify new variants associated with AD. METHODS: Our team performed a genome-wide association study in the Quebec Founder Population isolate to identify novel protective or risk genetic factors for late-onset sporadic AD and examined the impact of these variants on gene expression and AD pathology...
January 19, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Beth E Snitz, Tianxiu Wang, Yona Keich Cloonan, Erin Jacobsen, Chung-Chou H Chang, Tiffany F Hughes, M Ilyas Kamboh, Mary Ganguli
INTRODUCTION: We compared risk of progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) in an academic memory clinic versus a population-based study. METHODS: Older adults presenting at a memory clinic were classified as SCD (n = 113) or as noncomplainers (n = 82). Participants from a population study were classified as SCD (n = 592) and noncomplainers (n = 589) based on a memory complaint score. Annual follow-up performed for 3 years...
January 17, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Giovanni Di Guardo
No abstract text is available yet for this article.
January 17, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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