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

Yen-Feng Lin, Albert Vernon Smith, Thor Aspelund, Rebecca A Betensky, Jordan W Smoller, Vilmundur Gudnason, Lenore J Launer, Deborah Blacker
INTRODUCTION: We sought to examine the genetic overlap between vascular pathologies and Alzheimer's disease (AD) dementia, and the potential mediating role of vascular pathologies between AD-related genetic variants and late-life cognition. METHODS: For 2907 stroke-free older individuals, we examined the association of polygenic risk scores for AD dementia (ADPRSs) with vascular pathologies and with cognition. Mediation analyses addressed whether association between ADPRSs and cognition was mediated by a vascular pathology...
September 18, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Paul Brewster, Lisa Barnes, Mary Haan, Julene K Johnson, Jennifer J Manly, Anna María Nápoles, Rachel A Whitmer, Luis Carvajal-Carmona, Dawnte Early, Sarah Farias, Elizabeth Rose Mayeda, Rebecca Melrose, Oanh L Meyer, Adina Zeki Al Hazzouri, Ladson Hinton, Dan Mungas
In 2016, the UC Davis Latino Aging Research Resource Center and UC Davis Alzheimer's Disease Center brought together experts from across the country to consolidate current knowledge and identify future directions in aging and diversity research. This report disseminates the research priorities that emerged from this conference, building on an earlier Gerontological Society of America preconference. We review key racial/ethnic differences in cognitive aging and dementia and identify current knowledge gaps in the field...
September 18, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Shoichi Sasaki
INTRODUCTION: The objective of this study was to examine the prevalence of the coexistence of parkinsonism in patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD). METHODS: Outpatients were evaluated with Mini-Mental State Examination, Clinical Dementia Rating Scale, NIA-AA criteria, MRI, and 123 I-IMP SPECT (3D-SSP). Parkinsonism in patients diagnosed with MCI (Mini-Mental State Examination ≥24, n = 63) or mild AD (Mini-Mental State Examination 20-23, n = 43) was examined using the Unified Parkinson's Disease Rating Scale-III and 123 I-FP-CIT dopamine transporter SPECT...
September 14, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Yaakov Stern, Eider M Arenaza-Urquijo, David Bartrés-Faz, Sylvie Belleville, Marc Cantilon, Gael Chetelat, Michael Ewers, Nicolai Franzmeier, Gerd Kempermann, William S Kremen, Ozioma Okonkwo, Nikolaos Scarmeas, Anja Soldan, Chinedu Udeh-Momoh, Michael Valenzuela, Prashanthi Vemuri, Eero Vuoksimaa
Several concepts, which in the aggregate get might be used to account for "resilience" against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research...
September 14, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Kumar B Rajan, Jennifer Weuve, Lisa L Barnes, Robert S Wilson, Denis A Evans
INTRODUCTION: The trends in prevalence and incidence of Alzheimer's disease (AD) dementia remain uncertain. METHODS: A sample of 2794 participants with a clinical diagnosis for AD dementia were included. RESULTS: The 2010 census standardized prevalence of AD dementia was 14.5% (95% CI = 13.7-15.3), and annual incidence was 2.3% (1.7-2.9). Both prevalence and incidence showed substantial variation over time, but no secular trends. The prevalence of AD dementia did not change significantly from 14...
September 6, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Elżbieta Kuźma, Ilianna Lourida, Sarah F Moore, Deborah A Levine, Obioha C Ukoumunne, David J Llewellyn
INTRODUCTION: Stroke is an established risk factor for all-cause dementia, though meta-analyses are needed to quantify this risk. METHODS: We searched Medline, PsycINFO, and Embase for studies assessing prevalent or incident stroke versus a no-stroke comparison group and the risk of all-cause dementia. Random effects meta-analysis was used to pool adjusted estimates across studies, and meta-regression was used to investigate potential effect modifiers. RESULTS: We identified 36 studies of prevalent stroke (1...
August 25, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Gaël Nicolas, Rocio Acuna-Hidalgo, Michael J Keogh, Olivier Quenez, Marloes Steehouwer, Stefan Lelieveld, Stéphane Rousseau, Anne-Claire Richard, Manon S Oud, Florent Marguet, Annie Laquerrière, Chris M Morris, Johannes Attems, Colin Smith, Olaf Ansorge, Safa Al Sarraj, Thierry Frebourg, Dominique Campion, Didier Hannequin, David Wallon, Christian Gilissen, Patrick F Chinnery, Joris A Veltman, Alexander Hoischen
INTRODUCTION: A minority of patients with sporadic early-onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP, PSEN1, or PSEN2. We hypothesized that negatively screened patients may harbor somatic variants in these genes. METHODS: We applied an ultrasensitive approach based on single-molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic patients with AD (>80% exhibited an early onset, <66 years)...
August 13, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Anna Marseglia, Laura Fratiglioni, Grégoria Kalpouzos, Rui Wang, Lars Bäckman, Weili Xu
INTRODUCTION: The impact of prediabetes and diabetes on cognitive decline and the potential underlying mechanisms remain unclear. We investigated whether prediabetes and diabetes accelerate cognitive decline and brain aging, and the initial pathological changes linked to microvascular processes. METHODS: Nine-year longitudinal data from the Swedish National Study on Aging and Care-Kungsholmen (n = 2746, age ≥60 years) and the magnetic resonance imaging subsample (n = 455) were used...
August 13, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Yi Tang, Michael W Lutz, Yi Xing
The new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease has been developed to accelerate drug discovery and offer a common structure and language to construct new Alzheimer's disease conceptual models. However, as a "complex" disease, a model based on systems-level understanding is needed to accommodate the complex, interacting etiologic pathways and the system-level changes associated with Alzheimer's disease pathogenesis and interventions that are currently known and which will be identified in the future...
August 10, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Gene L Bowman, Loïc Dayon, Richard Kirkland, Jérôme Wojcik, Gwendoline Peyratout, India C Severin, Hugues Henry, Aikaterini Oikonomidi, Eugenia Migliavacca, Michael Bacher, Julius Popp
INTRODUCTION: Blood-brain barrier (BBB) breakdown is observed in older versus younger adults and in late-onset Alzheimer's disease versus age-matched controls, but its causes and consequences in aging are unclear. We tested the hypothesis that BBB breakdown is associated with cognitive decline and inflammation in nondemented elders. METHODS: Cerebrospinal fluid and serum inflammatory markers were measured using sandwich immunoassays in 120 subjects. Least Absolute Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid and serum signatures that best classified BBB impairment defined by the cerebrospinal fluid albumin index ≥9...
August 8, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Cecilia S Lee, Eric B Larson, Laura E Gibbons, Aaron Y Lee, Susan M McCurry, James D Bowen, Wayne C McCormick, Paul K Crane
INTRODUCTION: Identifying ophthalmic diseases associated with increased risk of Alzheimer's disease (AD) may enable better screening and understanding of those at risk of AD. METHODS: Diagnoses of glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) were based on International Classification of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in Thought study. The adjusted hazard ratio for developing probable or possible AD for recent (within 5 years) and established (>5 years) diagnoses were assessed...
August 2, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Andrea Vergallo, René-Sosata Bun, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Enrica Cavedo, Foudil Lamari, Marie-Odile Habert, Bruno Dubois, Roberto Floris, Francesco Garaci, Simone Lista, Harald Hampel
INTRODUCTION: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. METHODS: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored...
July 25, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Juan Antonio García-León, Alfredo Cabrera-Socorro, Kristel Eggermont, Ann Swijsen, Joke Terryn, Raheem Fazal, FatemehArefeh Nami, Laura Ordovás, Ana Quiles, Frederic Lluis, Lutgarde Serneels, Keimpe Wierda, Annerieke Sierksma, Mohamed Kreir, Francisco Pestana, Philip Van Damme, Bart De Strooper, Lieven Thorrez, Andreas Ebneth, Catherine M Verfaillie
Tauopathies are neurodegenerative diseases characterized by TAU protein-related pathology, including frontotemporal dementia and Alzheimer's disease among others. Mutant TAU animal models are available, but none of them faithfully recapitulates human pathology and are not suitable for drug screening. To create a new in vitro tauopathy model, we generated a footprint-free triple MAPT-mutant human induced pluripotent stem cell line (N279K, P301L, and E10+16 mutations) using clustered regularly interspaced short palindromic repeats-FokI and piggyBac transposase technology...
July 20, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
R Laforce, J P Soucy, L Sellami, C Dallaire-Théroux, F Brunet, D Bergeron, B L Miller, R Ossenkoppele
Molecular imaging techniques using 18 F-fluorodeoxyglucose, amyloid tracers, and, more recently, tau ligands have taken dementia research by storm and undoubtedly improved our understanding of neurodegenerative diseases. The ability to image in vivo the pathological substrates of degenerative diseases and visualize their downstream impact has led to improved models of pathogenesis, better differential diagnosis of atypical conditions, as well as focused subject selection and monitoring of treatment in clinical trials aimed at delaying or preventing the symptomatic phase of Alzheimer's disease...
July 17, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Shireen Sindi, Ingemar Kåreholt, Lena Johansson, Johan Skoog, Linnea Sjöberg, Hui-Xin Wang, Boo Johansson, Laura Fratiglioni, Hilkka Soininen, Alina Solomon, Ingmar Skoog, Miia Kivipelto
INTRODUCTION: Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk. METHODS: Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3-10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project)...
July 11, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Michael Navitsky, Abhinay D Joshi, Ian Kennedy, William E Klunk, Christopher C Rowe, Dean F Wong, Michael J Pontecorvo, Mark A Mintun, Michael D Devous
INTRODUCTION: Klunk et al. recently proposed a means of standardizing quantitation of amyloid burden from positron emission tomography scans to a common Centiloid scale, and we have applied that method to florbetapir. METHODS: Florbetapir and Pittsburgh compound B scans were acquired for 46 mixed clinical presentation subjects within 18 ± 20 days. Florbetapir and Pittsburgh compound B cortical standardized uptake value ratio (SUVr) values were well correlated for both standard Centiloid (R2  = 0...
July 10, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Enrica Cavedo, Patrizia A Chiesa, Marion Houot, Maria Teresa Ferretti, Michel J Grothe, Stefan J Teipel, Simone Lista, Marie-Odile Habert, Marie-Claude Potier, Bruno Dubois, Harald Hampel
INTRODUCTION: Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers. METHODS: Positron emission tomography brain amyloid load, neurodegeneration (hippocampus and basal forebrain volumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose-positron emission tomography metabolism), and brain resting-state functional connectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117)...
September 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Mark A Espeland, Owen Carmichael, Sevil Yasar, Christina Hugenschmidt, William Hazzard, Kathleen M Hayden, Stephen R Rapp, Rebecca Neiberg, Karen C Johnson, Siobhan Hoscheidt, Michelle M Mielke
INTRODUCTION: Type 2 diabetes mellitus and obesity may increase risks for cognitive decline as individuals age. It is unknown whether this results in different prevalences of cognitive impairment for women and men. METHODS: The Action for Health in Diabetes, a randomized controlled clinical trial of a 10-year intensive lifestyle intervention, adjudicated cases of cross-sectional cognitive impairment (mild cognitive impairment or dementia) 10-13 years after enrollment in 3802 individuals (61% women)...
September 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
May A Beydoun, Hind A Beydoun, Martine Elbejjani, Gregory A Dore, Alan B Zonderman
INTRODUCTION: Infectious agents were recently implicated in Alzheimer's disease (AD) and etiology of other dementias, notably Helicobacter pylori. METHODS: We tested associations of H. pylori seropositivity with incident all-cause and AD dementia and with AD-related mortality among US adults in a retrospective cohort study. Data from the National Health and Nutrition Surveys III, phase 1 (1988-1991) and 1999-2000 linked with Medicare and National Death Index registries, were used (baseline age ≥45 y, follow-up to 2013, Npooled  = 5927)...
September 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Michelle M Mielke, Maria Teresa Ferretti, M Florencia Iulita, Kathleen Hayden, Ara S Khachaturian
No abstract text is available yet for this article.
September 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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