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Publisher: Elsevier   (Total: 3175 journals)

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Showing 1 - 200 of 3175 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 8)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 28, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 90, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 33, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 376, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 235, SJR: 3.683, h-index: 202)
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Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
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Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
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Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 128, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
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Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
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Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
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Advances in Cancer Research     Full-text available via subscription   (Followers: 28, SJR: 2.215, h-index: 78)
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Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
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Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 2.314, h-index: 130)
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Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 6)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 42, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 54, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 14, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 7)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 1, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 375, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 333, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 9, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 429, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 50, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 42, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 189, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 61, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
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Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 165, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.18, h-index: 2)
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Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)

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Journal Cover Alzheimer's & Dementia
  [SJR: 4.289]   [H-I: 64]   [48 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1552-5260 - ISSN (Online) 1552-5279
   Published by Elsevier Homepage  [3175 journals]
  • NIA-AA Research Framework: Toward a biological definition of Alzheimer's
           disease
    • Authors: Clifford R. Jack; David A. Bennett; Kaj Blennow; Maria C. Carrillo; Billy Dunn; Samantha Budd Haeberlein; David M. Holtzman; William Jagust; Frank Jessen; Jason Karlawish; Enchi Liu; Jose Luis Molinuevo; Thomas Montine; Creighton Phelps; Katherine P. Rankin; Christopher C. Rowe; Philip Scheltens; Eric Siemers; Heather M. Snyder; Reisa Sperling; Cerise Elliott; Eliezer Masliah; Laurie Ryan; Nina Silverberg
      Pages: 535 - 562
      Abstract: Publication date: April 2018
      Source:Alzheimer's & Dementia, Volume 14, Issue 4
      Author(s): Clifford R. Jack, David A. Bennett, Kaj Blennow, Maria C. Carrillo, Billy Dunn, Samantha Budd Haeberlein, David M. Holtzman, William Jagust, Frank Jessen, Jason Karlawish, Enchi Liu, Jose Luis Molinuevo, Thomas Montine, Creighton Phelps, Katherine P. Rankin, Christopher C. Rowe, Philip Scheltens, Eric Siemers, Heather M. Snyder, Reisa Sperling
      In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

      PubDate: 2018-04-12T07:43:21Z
      DOI: 10.1016/j.jalz.2018.02.018
       
  • Doublecortin expression in CD8+ T-cells and microglia at sites of
           amyloid-β plaques: A potential role in shaping plaque pathology'
    • Authors: Michael S. Unger; Julia Marschallinger; Julia Kaindl; Barbara Klein; Mary Johnson; Ahmad A. Khundakar; Stefan Roßner; Michael T. Heneka; Sebastien Couillard-Despres; Ed Rockenstein; Eliezer Masliah; Johannes Attems; Ludwig Aigner
      Abstract: Publication date: Available online 7 April 2018
      Source:Alzheimer's & Dementia
      Author(s): Michael S. Unger, Julia Marschallinger, Julia Kaindl, Barbara Klein, Mary Johnson, Ahmad A. Khundakar, Stefan Roßner, Michael T. Heneka, Sebastien Couillard-Despres, Ed Rockenstein, Eliezer Masliah, Johannes Attems, Ludwig Aigner
      One characteristic of Alzheimer's disease is the formation of amyloid-β plaques, which are typically linked to neuroinflammation and surrounded by inflammatory cells such as microglia and infiltrating immune cells. Here, we describe nonneurogenic doublecortin (DCX) positive cells, DCX being generally used as a marker for young immature neurons, at sites of amyloid-β plaques in various transgenic amyloid mouse models and in human brains with plaque pathology. The plaque-associated DCX+ cells were not of neurogenic identity, instead most of them showed coexpression with markers for microglia (Iba1) and for phagocytosis (CD68 and TREM2). Another subpopulation of plaque-associated DCX+ cells was negative for Iba1 but was highly positive for the pan-leukocyte marker CD45. These hematopoietic cells were identified as CD3-and CD8-positive and CD4-negative T-cells. Peculiarly, the DCX+/Iba1+ microglia and DCX+/CD8+ T-cells were closely attached, suggesting that these two cell types are tightly interacting and that this interaction might shape plaque pathology.

      PubDate: 2018-04-12T07:43:21Z
      DOI: 10.1016/j.jalz.2018.02.017
       
  • Identifying dementia cases with routinely collected health data:
           A systematic review
    • Authors: Tim Wilkinson; Amanda Ly; Christian Schnier; Kristiina Rannikmäe; Kathryn Bush; Carol Brayne; Terence J. Quinn; Cathie L.M. Sudlow
      Abstract: Publication date: Available online 3 April 2018
      Source:Alzheimer's & Dementia
      Author(s): Tim Wilkinson, Amanda Ly, Christian Schnier, Kristiina Rannikmäe, Kathryn Bush, Carol Brayne, Terence J. Quinn, Cathie L.M. Sudlow
      Introduction Prospective, population-based studies can be rich resources for dementia research. Follow-up in many such studies is through linkage to routinely collected, coded health-care data sets. We evaluated the accuracy of these data sets for dementia case identification. Methods We systematically reviewed the literature for studies comparing dementia coding in routinely collected data sets to any expert-led reference standard. We recorded study characteristics and two accuracy measures—positive predictive value (PPV) and sensitivity. Results We identified 27 eligible studies with 25 estimating PPV and eight estimating sensitivity. Study settings and methods varied widely. For all-cause dementia, PPVs ranged from 33%–100%, but 16/27 were >75%. Sensitivities ranged from 21% to 86%. PPVs for Alzheimer's disease (range 57%–100%) were generally higher than those for vascular dementia (range 19%–91%). Discussion Linkage to routine health-care data can achieve a high PPV and reasonable sensitivity in certain settings. Given the heterogeneity in accuracy estimates, cohorts should ideally conduct their own setting-specific validation.

      PubDate: 2018-04-12T07:43:21Z
      DOI: 10.1016/j.jalz.2018.02.016
       
  • Effects of APOE-ε4 allele load on brain morphology in a cohort of
           middle-aged healthy individuals with enriched genetic risk for Alzheimer's
           disease
    • Authors: Raffaele Cacciaglia; José Luis Molinuevo; Carles Falcón; Anna Brugulat-Serrat; Gonzalo Sánchez-Benavides; Nina Gramunt; Manel Esteller; Sebastián Morán; Carolina Minguillón; Karine Fauria; Juan Domingo Gispert
      Abstract: Publication date: Available online 28 March 2018
      Source:Alzheimer's & Dementia
      Author(s): Raffaele Cacciaglia, José Luis Molinuevo, Carles Falcón, Anna Brugulat-Serrat, Gonzalo Sánchez-Benavides, Nina Gramunt, Manel Esteller, Sebastián Morán, Carolina Minguillón, Karine Fauria, Juan Domingo Gispert
      Introduction Apolipoprotein E (APOE)-ε4 is the major genetic risk factor for Alzheimer's disease. However, the dose-dependent impact of this allele on brain morphology of healthy individuals remains unclear. Methods We analyzed gray matter volumes (GMvs) in a sample of 533 healthy middle-aged individuals with a substantial representation of ε4-carriers (207 heterozygotes and 65 homozygotes). Results We found APOE-ε4 additive GMv reductions in the right hippocampus, caudate, precentral gyrus, and cerebellar crus. In these regions, the APOE genotype interacted with age, with homozygotes displaying lower GMv after the fifth decade of life. APOE-ε4 was also associated to greater GMv in the right thalamus, left occipital gyrus, and right frontal cortex. Discussion Our data indicate that APOE-ε4 exerts additive effects on GMv in regions relevant for Alzheimer's disease pathophysiology already in healthy individuals. These findings elucidate the mechanisms underlying the increased Alzheimer's disease risk in ε4-carriers, suggesting a dose-dependent disease vulnerability on the brain structure level.

      PubDate: 2018-04-12T07:43:21Z
      DOI: 10.1016/j.jalz.2018.01.016
       
  • Longitudinal decreases in multiple cerebrospinal fluid biomarkers of
           neuronal injury in symptomatic late onset Alzheimer's disease
    • Authors: Courtney L. Sutphen; Lena McCue; Elizabeth M. Herries; Chengjie Xiong; Jack H. Ladenson; David M. Holtzman; Anne M. Fagan
      Abstract: Publication date: Available online 23 March 2018
      Source:Alzheimer's & Dementia
      Author(s): Courtney L. Sutphen, Lena McCue, Elizabeth M. Herries, Chengjie Xiong, Jack H. Ladenson, David M. Holtzman, Anne M. Fagan
      Introduction Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design. Methods Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid status. Results Levels of injury markers were highly positively correlated. Despite elevated baseline levels as a function of clinical status and amyloid-positivity, within-person decreases in these measures were observed in the early symptomatic, amyloid-positive Alzheimer's disease group. Discussion Knowledge of within-person biomarker change will impact interpretation of biomarker outcomes in clinical trials that are dependent on disease stage.

      PubDate: 2018-04-12T07:43:21Z
      DOI: 10.1016/j.jalz.2018.01.012
       
  • Elevated DNA methylation across a 48-kb region spanning the HOXA gene
           cluster is associated with Alzheimer's disease neuropathology
    • Authors: Rebecca G. Smith; Eilis Hannon; Philip L. De Jager; Lori Chibnik; Simon J. Lott; Daniel Condliffe; Adam R. Smith; Vahram Haroutunian; Claire Troakes; Safa Al-Sarraj; David A. Bennett; John Powell; Simon Lovestone; Leonard Schalkwyk; Jonathan Mill; Katie Lunnon
      Abstract: Publication date: Available online 15 March 2018
      Source:Alzheimer's & Dementia
      Author(s): Rebecca G. Smith, Eilis Hannon, Philip L. De Jager, Lori Chibnik, Simon J. Lott, Daniel Condliffe, Adam R. Smith, Vahram Haroutunian, Claire Troakes, Safa Al-Sarraj, David A. Bennett, John Powell, Simon Lovestone, Leonard Schalkwyk, Jonathan Mill, Katie Lunnon
      Introduction Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain. Methods We performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740). Results We identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster. A meta-analysis of the top-ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10−18). Discussion We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation.

      PubDate: 2018-03-19T22:39:37Z
      DOI: 10.1016/j.jalz.2018.01.017
       
  • Association of branched-chain amino acids and other circulating
           metabolites with risk of incident dementia and Alzheimer's disease: A
           prospective study in eight cohorts
    • Authors: 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
      Abstract: Publication date: Available online 6 March 2018
      Source:Alzheimer's & Dementia
      Author(s): 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. Results Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Discussion Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology.

      PubDate: 2018-03-07T15:43:11Z
      DOI: 10.1016/j.jalz.2018.01.003
       
  • Cerebrospinal fluid biomarkers measured by Elecsys assays compared to
           amyloid imaging
    • Authors: 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
      Abstract: Publication date: Available online 2 March 2018
      Source:Alzheimer's & Dementia
      Author(s): 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. Aβ40 was measured with the IBL plate-based assay. Positron emission tomography with Pittsburgh Compound B was performed less than 1 year from CSF collection. Results Ratios of CSF biomarkers (total tau/Aβ42, phosphorylated tau-181/Aβ42, and Aβ42/Aβ40) best discriminated Pittsburgh Compound B–positive from Pittsburgh Compound B–negative individuals. Discussion CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers.

      PubDate: 2018-03-07T15:43:11Z
      DOI: 10.1016/j.jalz.2018.01.013
       
  • Disentangling the biological pathways involved in early features of
           Alzheimer's disease in the Rotterdam Study
    • Authors: 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
      Abstract: Publication date: Available online 1 March 2018
      Source:Alzheimer's & Dementia
      Author(s): 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. Results The risk score capturing endocytosis pathway was significantly associated with mild cognitive impairment (P = 1.44 × 10−4). Immune response (P = .016) and clathrin/AP2 adaptor complex pathway (P = 3.55 × 10−3) excluding apolipoprotein E also showed modest association with white matter lesions but did not sustain Bonferroni correction (P = 9.09 × 10−4). Discussion Our study suggests that the clinical spectrum of early AD pathology is explained by different biological pathways, in particular, the endocytosis, clathrin/AP2 adaptor complex, and immune response pathways, that are independent of apolipoprotein E (APOE).

      PubDate: 2018-03-07T15:43:11Z
      DOI: 10.1016/j.jalz.2018.01.005
       
  • CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and
           predict clinical progression: A study of fully automated immunoassays in
           BioFINDER and ADNI cohorts
    • Authors: 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
      Abstract: Publication date: Available online 1 March 2018
      Source:Alzheimer's & Dementia
      Author(s): 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 [18F]flutemetamol PET in Swedish BioFINDER (n = 277) and validated against [18F]florbetapir PET in Alzheimer's Disease Neuroimaging Initiative (n = 646). Clinical progression in patients with mild cognitive impairment (n = 619) was studied. Results CSF total tau/Aβ(1–42) and phosphorylated tau/Aβ(1–42) ratios were highly concordant with PET classification in BioFINDER (overall percent agreement: 90%; area under the curve: 94%). The CSF biomarker statuses established by predefined cutoffs were highly concordant with PET classification in Alzheimer's Disease Neuroimaging Initiative (overall percent agreement: 89%–90%; area under the curves: 96%) and predicted greater 2-year clinical decline in patients with mild cognitive impairment. Strikingly, tau/Aβ ratios were as accurate as semiquantitative PET image assessment in predicting visual read–based outcomes. Discussion Elecsys CSF biomarker assays may provide reliable alternatives to PET in Alzheimer's disease diagnosis.

      PubDate: 2018-03-07T15:43:11Z
      DOI: 10.1016/j.jalz.2018.01.010
       
  • Plasma amyloid levels within the Alzheimer's process and correlations with
           central biomarkers
    • Authors: 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; Olivier Hanon; Frédéric Blanc; Yasmina Boudali; Audrey Gabelle; Marie–Laure Seux; Hermine Lenoir; Catherine Bayle; Stéphanie Bombois; Xavier Deleuk; Florence Moulin; Emmanuelle Duron; Florence Latour; Matthieu Plichart; Sophie Pichierri; Galdric Orvoën; Evelyne Galbrun; Giovanni Castelnovo; Lisette Volpe–Gillot; Florien Labourée; Pascaline Cassagnaud; Claire Paquet; Françoise Lala; Julien Dumurgier; Anne–Sophie Rigaud; Christine Perret–Guillaume; Eliana Alonso; Foucaud du Boisgueheneuc; Laurence Hugonot–Diener; Adeline Rollin–Sillaire; Olivier Martinaud; Clémence Boully; Yann Spivac; Agnès Devendeville; Joël Belmin; Philippe–Henri Robert; Thierry Dantoine; Laure Caillard; David Wallon; Didier Hannequin; Nathalie Sastre; Sophie Haffen; Anna Kearney–Schwartz; Jean–Luc Novella; Vincent Deramecourt; Valérie Chauvire; Gabiel Abitbol; Nathalie Schwald; Caroline Hommet; François Sellal; Marie–Ange Cariot; Mohamed Abdellaoui; Sarah Benisty; Salim Gherabli; Pierre Anthony; Frédéric Bloch; Nathalie Charasz; Sophie Chauvelier; Jean–Yves Gaubert; Guillaume Sacco; Olivier Guerin; Jacques Boddaert; Marc Paccalin; Marie–Anne Mackowiak; Marie–Thérèse Rabus; Valérie Gissot; Athanase Benetos; Candice Picard; Céline Guillemaud; Claire Gervais; Jaques Hugon; Jean–Marc Michel; Jean–Philippe David; Marion Paulin; Pierre–Jean Ousset; Pierre Vandel; Sylvie Pariel; Vincent Camus; Anne Chawakilian; Léna Joffredo; Anne–Cécile Troussiere; Cécile Adam; Diane Dupuy; Elèna Paillaud; Hélène Briault; Isabelle Saulnier; Karl Mondon; Marie–Agnès Picat; Marie Laurent; Olivier Godefroy; Rezki Daheb; Stéphanie Libercier; Djamila Krabchi; Marie Chupin; Jean–Sébastien Vidal; Edouard Chaussade; Sylvain Lehmann; Suzanna Schraen-Maschke
      Abstract: Publication date: Available online 17 February 2018
      Source:Alzheimer's & Dementia
      Author(s): 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. Results Plasma Aβ1–42 and Aβ1–40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ1–42 and P = .04 for Aβ1–40). Globally, plasma Aβ1–42 correlated with age, Mini–Mental State Examination, and APOE ε4 allele. Plasma Aβ1–42 correlated with all CSF biomarkers in MCI but only with CSF Aβ42 in AD. Conclusion Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.

      PubDate: 2018-02-26T10:48:17Z
      DOI: 10.1016/j.jalz.2018.01.004
       
  • CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's
           disease
    • Authors: Justin Miron; Cynthia Picard; Nathalie Nilsson; Josée Frappier; Doris Dea; Louise Théroux; Judes Poirier
      Abstract: Publication date: Available online 19 January 2018
      Source:Alzheimer's & Dementia
      Author(s): 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. Results The rs10984186 variant is associated with an increased risk of developing AD and with a higher CDK5RAP2 mRNA prevalence in the hippocampus. On the other hand, the rs4837766 variant, which is among the best cis-expression quantitative trait loci in the CDK5RAP2 gene, is associated with lower mild cognitive impairment/AD risk and conversion rate. Discussion The rs10984186 risk and rs4837766 protective polymorphic variants of the CDK5RAP2 gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expression of this gene.

      PubDate: 2018-01-26T20:31:48Z
      DOI: 10.1016/j.jalz.2017.12.004
       
  • Assembly of 809 whole mitochondrial genomes with clinical, imaging, and
           fluid biomarker phenotyping
    • Authors: Perry G. Ridge; Mark E. Wadsworth; Justin B. Miller; Andrew J. Saykin; Robert C. Green; John S.K. Kauwe
      Abstract: Publication date: Available online 5 January 2018
      Source:Alzheimer's & Dementia
      Author(s): Perry G. Ridge, Mark E. Wadsworth, Justin B. Miller, Andrew J. Saykin, Robert C. Green, John S.K. Kauwe
      Introduction Mitochondrial genetics are an important but largely neglected area of research in Alzheimer's disease. A major impediment is the lack of data sets. Methods We used an innovative, rigorous approach, combining several existing tools with our own, to accurately assemble and call variants in 809 whole mitochondrial genomes. Results To help address this impediment, we prepared a data set that consists of 809 complete and annotated mitochondrial genomes with samples from the Alzheimer's Disease Neuroimaging Initiative. These whole mitochondrial genomes include rich phenotyping, such as clinical, fluid biomarker, and imaging data, all of which is available through the Alzheimer's Disease Neuroimaging Initiative website. Genomes are cleaned, annotated, and prepared for analysis. Discussion These data provide an important resource for investigating the impact of mitochondrial genetic variation on risk for Alzheimer's disease and other phenotypes that have been measured in the Alzheimer's Disease Neuroimaging Initiative samples.

      PubDate: 2018-01-15T16:45:29Z
      DOI: 10.1016/j.jalz.2017.11.013
       
  • Exploring APOE genotype effects on AD risk and β-amyloid burden in
           individuals with subjective cognitive decline: The FACEHBI study baseline
           results
    • Authors: Sonia Moreno-Grau; Octavio Rodriguez; Angela Sanabria; Alba Perez; Domingo Sanchez; Carla Abdelnour; Sergi Valero; Isabel Hernandez; Maitee Rosende-Roca; Ana Mauleon; Liliana Vargas; Monserrat Alegret; Ana Espinosa; Gemma Ortega; Marina Guitart; Anna Gailhajanet; Itziar de Rojas; Oscar Sotolongo-Grau; Susana Ruiz; Marina Tarragona; Judit Serra; Elvira Martín; Esther Peleja; Francisco Lomeña; Francisco Campos; Assumpta Vivas; Miguel Angel Tejero; Joan Giménez; Pedro Pesini; Manuel Sarasa; Gabriel Martinez; Marta Gómez Chiari; Adelina Orellana; Lluis Tarraga; Agustín Ruiz; Mercè Boada
      Abstract: Publication date: Available online 20 November 2017
      Source:Alzheimer's & Dementia
      Author(s): 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. Results Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE Ɛ4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. Discussion The FACEHBI sample presents APOE Ɛ4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.

      PubDate: 2017-11-21T07:15:58Z
      DOI: 10.1016/j.jalz.2017.06.208
       
  • Multidomain lifestyle intervention benefits a large elderly population at
           risk for cognitive decline and dementia regardless of baseline
           characteristics: The FINGER trial
    • Authors: Anna Rosenberg; Alina Solomon; Tiia Ngandu; Esko Levälahti; Tiina Laatikainen; Teemu Paajanen; Tuomo Hänninen; Riitta Antikainen; Timo Strandberg; Hilkka Soininen; Miia Kivipelto
      Abstract: Publication date: Available online 19 October 2017
      Source:Alzheimer's & Dementia
      Author(s): 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). Participants were randomized 1:1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses. Results Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini–Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05). Conclusions The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia.

      PubDate: 2017-10-22T00:46:21Z
      DOI: 10.1016/j.jalz.2017.06.138
       
  • Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau
           deposition in Alzheimer's disease
    • Authors: Antoine Leuzy; Elena Rodriguez-Vieitez; Laure Saint-Aubert; Konstantinos Chiotis; Ove Almkvist; Irina Savitcheva; My Jonasson; Mark Lubberink; Anders Wall; Gunnar Antoni; Agneta Nordberg
      Abstract: Publication date: Available online 19 December 2017
      Source:Alzheimer's & Dementia
      Author(s): Antoine Leuzy, Elena Rodriguez-Vieitez, Laure Saint-Aubert, Konstantinos Chiotis, Ove Almkvist, Irina Savitcheva, My Jonasson, Mark Lubberink, Anders Wall, Gunnar Antoni, Agneta Nordberg
      Introduction Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single positron emission tomography study can provide both functional and molecular information. Methods We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change. Results Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317. Discussion Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.

      PubDate: 2017-12-26T18:07:37Z
      DOI: 10.1016/j.jalz.2017.11.008
       
  • The aged rhesus macaque manifests Braak stage III/IV Alzheimer's-like
           pathology
    • Authors: Constantinos D. Paspalas; Becky C. Carlyle; Shannon Leslie; Todd M. Preuss; Johanna L. Crimins; Anita J. Huttner; Christopher H. van Dyck; Douglas L. Rosene; Angus C. Nairn; Amy F.T. Arnsten
      Abstract: Publication date: Available online 11 December 2017
      Source:Alzheimer's & Dementia
      Author(s): Constantinos D. Paspalas, Becky C. Carlyle, Shannon Leslie, Todd M. Preuss, Johanna L. Crimins, Anita J. Huttner, Christopher H. van Dyck, Douglas L. Rosene, Angus C. Nairn, Amy F.T. Arnsten
      Introduction An animal model of late-onset Alzheimer's disease is needed to research what causes degeneration in the absence of dominant genetic insults and why the association cortex is particularly vulnerable to degeneration. Methods We studied the progression of tau and amyloid cortical pathology in the aging rhesus macaque using immunoelectron microscopy and biochemical assays. Results Aging macaques exhibited the same qualitative pattern and sequence of tau and amyloid cortical pathology as humans, reaching Braak stage III/IV. Pathology began in the young-adult entorhinal cortex with protein kinase A-phosphorylation of tau, progressing to fibrillation with paired helical filaments and mature tangles in oldest animals. Tau pathology in the dorsolateral prefrontal cortex paralleled but lagged behind the entorhinal cortex, not afflicting the primary visual cortex. Discussion The aging rhesus macaque provides the long-sought animal model for exploring the etiology of late-onset Alzheimer's disease and for testing preventive strategies.

      PubDate: 2017-12-12T07:32:16Z
      DOI: 10.1016/j.jalz.2017.11.005
       
  • Delirium symptoms are associated with decline in cognitive function
           between ages 53 and 69 years: Findings from a British birth cohort study
    • Authors: A. Tsui; D. Kuh; M. Richards; D. Davis
      Abstract: Publication date: Available online 21 November 2017
      Source:Alzheimer's & Dementia
      Author(s): A. Tsui, D. Kuh, M. Richards, D. Davis
      Introduction Few population studies have investigated whether longitudinal decline after delirium in mid-to-late life might affect specific cognitive domains. Methods Participants from a birth cohort completing assessments of search speed, verbal memory, and the Addenbrooke's Cognitive Examination at age 69 were asked about delirium symptoms between ages 60 and 69 years. Linear regression models estimated associations between delirium symptoms and cognitive outcomes. Results Period prevalence of delirium between 60 and 69 years was 4% (95% confidence interval 3.2%–4.9%). Self-reported symptoms of delirium over the seventh decade were associated with worse scores in the Addenbrooke's Cognitive Examination (−1.7 points; 95% confidence interval −3.2, −0.1; P = .04). In association with delirium symptoms, verbal memory scores were initially lower, with subsequent decline in search speed by the age of 69 years. These effects were independent of other Alzheimer's risk factors. Discussion Delirium symptoms may be common even at relatively younger ages, and their presence may herald cognitive decline, particularly in search speed, over this time period.

      PubDate: 2017-12-01T21:30:01Z
      DOI: 10.1016/j.jalz.2017.08.018
       
  • Body mass index and risk of dementia: Analysis of individual-level data
           from 1.3 million individuals
    • Authors: Mika Kivimäki; Ritva Luukkonen; G. David Batty; Jane E. Ferrie; Jaana Pentti; Solja T. Nyberg; Martin J. Shipley; Lars Alfredsson; Eleonor I. Fransson; Marcel Goldberg; Anders Knutsson; Markku Koskenvuo; Eeva Kuosma; Maria Nordin; Sakari B. Suominen; Töres Theorell; Eero Vuoksimaa; Peter Westerholm; Hugo Westerlund; Marie Zins; Miia Kivipelto; Jussi Vahtera; Jaakko Kaprio; Archana Singh-Manoux; Markus Jokela
      Abstract: Publication date: Available online 21 November 2017
      Source:Alzheimer's & Dementia
      Author(s): Mika Kivimäki, Ritva Luukkonen, G. David Batty, Jane E. Ferrie, Jaana Pentti, Solja T. Nyberg, Martin J. Shipley, Lars Alfredsson, Eleonor I. Fransson, Marcel Goldberg, Anders Knutsson, Markku Koskenvuo, Eeva Kuosma, Maria Nordin, Sakari B. Suominen, Töres Theorell, Eero Vuoksimaa, Peter Westerholm, Hugo Westerlund, Marie Zins, Miia Kivipelto, Jussi Vahtera, Jaakko Kaprio, Archana Singh-Manoux, Markus Jokela
      Introduction Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. Methods We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis. Results Hazard ratios per 5-kg/m2 increase in BMI for dementia were 0.71 (95% confidence interval = 0.66–0.77), 0.94 (0.89–0.99), and 1.16 (1.05–1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis. Conclusions The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short.

      PubDate: 2017-12-01T21:30:01Z
      DOI: 10.1016/j.jalz.2017.09.016
       
  • Added value of 18F-florbetaben amyloid PET in the diagnostic workup of
           most complex patients with dementia in France: A naturalistic study
    • Authors: 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
      Abstract: Publication date: Available online 4 November 2017
      Source:Alzheimer's & Dementia
      Author(s): 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.gov: NCT02681172). Results Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases. Discussion High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.

      PubDate: 2017-11-05T15:50:28Z
      DOI: 10.1016/j.jalz.2017.09.009
       
  • Conserved brain myelination networks are altered in Alzheimer's and other
           neurodegenerative diseases
    • Authors: 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
      Abstract: Publication date: Available online 31 October 2017
      Source:Alzheimer's & Dementia
      Author(s): 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. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples. Discussion Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.

      PubDate: 2017-11-05T15:50:28Z
      DOI: 10.1016/j.jalz.2017.09.012
       
  • Neuropsychiatric symptoms as risk factors of dementia in a Mexican
           population: A 10/66 Dementia Research Group study
    • Authors: Isaac Acosta; Guilherme Borges; Rebeca Aguirre-Hernandez; Ana Luisa Sosa; Martin Prince
      Abstract: Publication date: Available online 10 October 2017
      Source:Alzheimer's & Dementia
      Author(s): 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. Results Five neuropsychiatric symptoms were associated with incident dementia: delusions, hallucinations, anxiety, aberrant motor behavior, and depression. The simultaneous presence of two symptoms had a relative risk, adjusted for mild cognitive impairment, diabetes, indicators of cognitive function, and sociodemographic factors, of 1.9 (95% confidence interval, 1.2–2.9), whereas the presence of three to five, similarly adjusted, had a relative risk of 3.0 (95% confidence interval, 1.9–4.8). Discussion Neuropsychiatric symptoms are common in predementia states and may independently contribute as risk factors for developing dementia.

      PubDate: 2017-11-05T15:50:28Z
      DOI: 10.1016/j.jalz.2017.08.015
       
  • Amyloid beta synaptotoxicity is Wnt–planar cell polarity dependent
           and blocked by fasudil
    • Authors: Katherine J. Sellers; Christina Elliott; Joshua Jackson; Anshua Ghosh; Elena Ribe; Ana Rojo-Sanchís; 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
      Abstract: Publication date: Available online 19 October 2017
      Source:Alzheimer's & Dementia
      Author(s): Katherine J. Sellers, Christina Elliott, Joshua Jackson, Anshua Ghosh, Elena Ribe, Ana Rojo-Sanchís, 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 basis of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease (AD) sufferer's amyloid beta (Aβ) peptides aggregate to form senile plaques but as soluble peptides that 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 Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway. Results We demonstrate that Aβ synaptotoxicity is also Dkk1 and Wnt-PCP dependent, mediated by the arm of Wnt-PCP regulating actin cytoskeletal dynamics via Daam1, RhoA, and ROCK, and can be blocked by the drug fasudil. Discussion Our data place Wnt-PCP signaling at the center of AD neuropathology and indicate that fasudil could be repositioned as a treatment for AD.

      PubDate: 2017-10-22T00:46:21Z
      DOI: 10.1016/j.jalz.2017.09.008
       
  • Apolipoprotein E4 inhibits autophagy gene products through direct,
           specific binding to CLEAR motifs
    • Authors: Paul A. Parcon; Meenakshisundaram Balasubramaniam; Srinivas Ayyadevara; Richard A. Jones; Ling Liu; Robert J. Shmookler Reis; Steven W. Barger; Robert E. Mrak; W. Sue T. Griffin
      Abstract: Publication date: Available online 22 September 2017
      Source:Alzheimer's & Dementia
      Author(s): Paul A. Parcon, Meenakshisundaram Balasubramaniam, Srinivas Ayyadevara, Richard A. Jones, Ling Liu, Robert J. Shmookler Reis, Steven W. Barger, Robert E. Mrak, W. Sue T. Griffin
      Introduction Alzheimer apolipoprotein E (APOE) ε4,4 carriers have earlier disease onset and more protein aggregates than patients with other APOE genotypes. Autophagy opposes aggregation, and important autophagy genes are coordinately regulated by transcription factor EB (TFEB) binding to “coordinated lysosomal expression and regulation” (CLEAR) DNA motifs. Methods Autophagic gene expression was assessed in brains of controls and Alzheimer's disease (AD) patients parsed by APOE genotype and in a glioblastoma cell line expressing either ApoE3 or ApoE4. Computational modeling assessed interactions between ApoE and mutated ApoE with CLEAR or modified DNA. Results Three TFEB-regulated mRNA transcripts—SQSTM1/p62, MAP1LC3B, and LAMP2—were lower in AD ε4,4 than in AD ε3,3 brains. Computational modeling predicted avid specific binding of ApoE4 to CLEAR motifs. ApoE was found in cellular nuclei, and in vitro binding assays suggest competition between ApoE4 and TFEB at CLEAR sites. Conclusion ApoE4-CLEAR interactions may account for suppressed autophagy in APOE ε4,4 carriers and, in this way, contribute to earlier AD onset.

      PubDate: 2017-09-23T22:22:21Z
      DOI: 10.1016/j.jalz.2017.07.754
       
  • Dementia prevalence and incidence in a federation of European Electronic
           Health Record databases—The European Medical Informatics Framework
           resource
    • Authors: Gayan Perera; Lars Pedersen; David Ansel; Myriam Alexander; H. Michael Arrighi; Paul Avillach; Nadia Foskett; Rosa Gini; Mark F. Gordon; Usha Gungabissoon; Miguel-Angel Mayer; Gerald Novak; Peter Rijnbeek; Gianluca Trifirò; Johan van der Lei; Pieter J. Visser; Robert Stewart
      Abstract: Publication date: Available online 21 July 2017
      Source:Alzheimer's & Dementia
      Author(s): Gayan Perera, Lars Pedersen, David Ansel, Myriam Alexander, H. Michael Arrighi, Paul Avillach, Nadia Foskett, Rosa Gini, Mark F. Gordon, Usha Gungabissoon, Miguel-Angel Mayer, Gerald Novak, Peter Rijnbeek, Gianluca Trifirò, Johan van der Lei, Pieter J. Visser, Robert Stewart
      Introduction The European Medical Information Framework consortium has assembled electronic health record (EHR) databases for dementia research. We calculated dementia prevalence and incidence in 25 million persons from 2004 to 2012. Methods Six EHR databases (three primary care and three secondary care) from five countries were interrogated. Dementia was ascertained by consensus harmonization of clinical/diagnostic codes. Annual period prevalences and incidences by age and gender were calculated and meta-analyzed. Results The six databases contained 138,625 dementia cases. Age-specific prevalences were around 30% of published estimates from community samples and incidences were around 50%. Pooled prevalences had increased from 2004 to 2012 in all age groups but pooled incidences only after age 75 years. Associations with age and gender were stable over time. Discussion The European Medical Information Framework initiative supports EHR data on unprecedented number of people with dementia. Age-specific prevalences and incidences mirror estimates from community samples in pattern at levels that are lower but increasing over time.

      PubDate: 2017-07-21T14:54:26Z
      DOI: 10.1016/j.jalz.2017.06.2270
       
  • Cerebral hypoperfusion is not associated with an increase in β-amyloid
           pathology in middle-aged or elderly people
    • Authors: O. Hansson; S. Palmqvist; H. Ljung; T. Cronberg; D. van Westen; R. Smith
      Abstract: Publication date: Available online 15 July 2017
      Source:Alzheimer's & Dementia
      Author(s): O. Hansson, S. Palmqvist, H. Ljung, T. Cronberg, D. van Westen, R. Smith
      Introduction It is hypothesized that cerebral hypoperfusion promotes the development of Alzheimer pathology. We therefore studied whether longstanding cerebral hypoperfusion is associated with Alzheimer pathology in nondemented humans. Methods Cerebral blood flow and β-amyloid (18F-Flutemetamol) positron emission tomography retention were assessed in eleven patients with unilateral occlusion of precerebral arteries resulting in chronic and uneven hypoperfusion. A subset of patients underwent tau (18F-AV-1451) positron emission tomography. Results The blood flow was significantly reduced on the affected side of the brain in patients with unilateral occlusion of the internal carotid artery or stenosis of the middle cerebral artery. However, the cortical uptake of 18F-Flutemetamol or 18F-AV-1451 was not altered. Discussion Our results suggest that longstanding cerebral hypoperfusion in humans does not result in accumulation of β-amyloid fibrils or tau aggregates.

      PubDate: 2017-07-21T14:54:26Z
      DOI: 10.1016/j.jalz.2017.06.2265
       
  • Consensus classification of posterior cortical atrophy
    • Authors: Sebastian J. Crutch; Jonathan M. Schott; Gil D. Rabinovici; Melissa Murray; Julie S. Snowden; Wiesje M. van der Flier; Bradford C. Dickerson; Rik Vandenberghe; Samrah Ahmed; Thomas H. Bak; Bradley F. Boeve; Christopher Butler; Stefano F. Cappa; Mathieu Ceccaldi; Leonardo Cruz de Souza; Bruno Dubois; Olivier Felician; Douglas Galasko; Jonathan Graff-Radford; Neill R. Graff-Radford; Patrick R. Hof; Pierre Krolak-Salmon; Manja Lehmann; Eloi Magnin; Mario F. Mendez; Peter J. Nestor; Chiadi U. Onyike; Victoria S. Pelak; Yolande Pijnenburg; Silvia Primativo; Martin N. Rossor; Natalie S. Ryan; Philip Scheltens; Timothy J. Shakespeare; Aida Suárez González; David F. Tang-Wai; Keir X.X. Yong; Maria Carrillo; Nick C. Fox
      Abstract: Publication date: Available online 2 March 2017
      Source:Alzheimer's & Dementia
      Author(s): Sebastian J. Crutch, Jonathan M. Schott, Gil D. Rabinovici, Melissa Murray, Julie S. Snowden, Wiesje M. van der Flier, Bradford C. Dickerson, Rik Vandenberghe, Samrah Ahmed, Thomas H. Bak, Bradley F. Boeve, Christopher Butler, Stefano F. Cappa, Mathieu Ceccaldi, Leonardo Cruz de Souza, Bruno Dubois, Olivier Felician, Douglas Galasko, Jonathan Graff-Radford, Neill R. Graff-Radford, Patrick R. Hof, Pierre Krolak-Salmon, Manja Lehmann, Eloi Magnin, Mario F. Mendez, Peter J. Nestor, Chiadi U. Onyike, Victoria S. Pelak, Yolande Pijnenburg, Silvia Primativo, Martin N. Rossor, Natalie S. Ryan, Philip Scheltens, Timothy J. Shakespeare, Aida Suárez González, David F. Tang-Wai, Keir X.X. Yong, Maria Carrillo, Nick C. Fox
      Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.

      PubDate: 2017-03-02T15:50:30Z
      DOI: 10.1016/j.jalz.2017.01.014
       
  • The Alu neurodegeneration hypothesis: A primate-specific mechanism for
           neuronal transcription noise, mitochondrial dysfunction,
           and manifestation of neurodegenerative disease
    • Authors: Peter A. Larsen; Michael W. Lutz; Kelsie E. Hunnicutt; Mirta Mihovilovic; Ann M. Saunders; Anne D. Yoder; Allen D. Roses
      Abstract: Publication date: Available online 24 February 2017
      Source:Alzheimer's & Dementia
      Author(s): Peter A. Larsen, Michael W. Lutz, Kelsie E. Hunnicutt, Mirta Mihovilovic, Ann M. Saunders, Anne D. Yoder, Allen D. Roses
      It is hypothesized that retrotransposons have played a fundamental role in primate evolution and that enhanced neurologic retrotransposon activity in humans may underlie the origin of higher cognitive function. As a potential consequence of this enhanced activity, it is likely that neurons are susceptible to deleterious retrotransposon pathways that can disrupt mitochondrial function. An example is observed in the TOMM40 gene, encoding a β-barrel protein critical for mitochondrial preprotein transport. Primate-specific Alu retrotransposons have repeatedly inserted into TOMM40 introns and at least one variant associated with late-onset Alzheimer's disease originated from an Alu insertion event. We provide evidence of enriched Alu content in mitochondrial genes and postulate that Alus can disrupt mitochondrial populations in neurons, thereby setting the stage for progressive neurologic dysfunction. This Alu neurodegeneration hypothesis is compatible with decades of research and offers a plausible mechanism for the disruption of neuronal mitochondrial homeostasis, ultimately cascading into neurodegenerative disease.

      PubDate: 2017-03-02T15:50:30Z
      DOI: 10.1016/j.jalz.2017.01.017
       
  • Transethnic genome-wide scan identifies novel Alzheimer's disease loci
    • Authors: Gyungah Jun; Jaeyoon Chung Jesse Mez Robert Barber Gary Beecham
      Abstract: Publication date: Available online 7 February 2017
      Source:Alzheimer's & Dementia
      Author(s): Gyungah R. Jun, Jaeyoon Chung, Jesse Mez, Robert Barber, Gary W. Beecham, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Minerva M. Carrasquillo, Paul K. Crane, Carlos Cruchaga, Philip De Jager, Nilufer Ertekin-Taner, Denis Evans, M. Danielle Fallin, Tatiana M. Foroud, Robert P. Friedland, Alison M. Goate, Neill R. Graff-Radford, Hugh Hendrie, Kathleen S. Hall, Kara L. Hamilton-Nelson, Rivka Inzelberg, M. Ilyas Kamboh, John S.K. Kauwe, Walter A. Kukull, Brian W. Kunkle, Ryozo Kuwano, Eric B. Larson, Mark W. Logue, Jennifer J. Manly, Eden R. Martin, Thomas J. Montine, Shubhabrata Mukherjee, Adam Naj, Eric M. Reiman, Christiane Reitz, Richard Sherva, Peter H. St. George-Hyslop, Timothy Thornton, Steven G. Younkin, Badri N. Vardarajan, Li-San Wang, Jens R. Wendlund, Ashley R. Winslow, Jonathan Haines, Richard Mayeux, Margaret A. Pericak-Vance, Gerard Schellenberg, Kathryn L. Lunetta, Lindsay A. Farrer
      Background Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)–based tests (P < 5 × 10−8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the APOE ɛ4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10−6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10−6). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

      PubDate: 2017-02-10T13:30:54Z
       
  • Factors associated with the quality of life of family carers of people
           with dementia: A systematic review
    • Authors: Nicolas Farina; Thomas E. Page; Stephanie Daley; Anna Brown; Ann Bowling; Thurstine Basset; Gill Livingston; Martin Knapp; Joanna Murray; Sube Banerjee
      Abstract: Publication date: Available online 5 February 2017
      Source:Alzheimer's & Dementia
      Author(s): Nicolas Farina, Thomas E. Page, Stephanie Daley, Anna Brown, Ann Bowling, Thurstine Basset, Gill Livingston, Martin Knapp, Joanna Murray, Sube Banerjee
      Introduction Family carers of people with dementia are their most important support in practical, personal, and economic terms. Carers are vital to maintaining the quality of life (QOL) of people with dementia. This review aims to identify factors related to the QOL of family carers of people with dementia. Methods Searches on terms including “carers,” “dementia,” “family,” and “quality of life” in research databases. Findings were synthesized inductively, grouping factors associated with carer QOL into themes. Results A total of 909 abstracts were identified. Following screening, lateral searches, and quality appraisal, 41 studies (n = 5539) were included for synthesis. A total of 10 themes were identified: demographics; carer–patient relationship; dementia characteristics; demands of caring; carer health; carer emotional well-being; support received; carer independence; carer self-efficacy; and future. Discussion The quality and level of evidence supporting each theme varied. We need further research on what factors predict carer QOL in dementia and how to measure it.

      PubDate: 2017-02-10T13:30:54Z
      DOI: 10.1016/j.jalz.2016.12.010
       
  • Synergistic interaction between amyloid and tau predicts the
           progression to dementia
    • Authors: Tharick A. Pascoal; Sulantha S. Mathotaarachchi; Monica Shin; Andrea Lessa Benedet; Min Su Kang; Sara Mohades; Thomas Beaudry; Jean-Paul Soucy; Serge Gauthier; Pedro Rosa-Neto
      Abstract: Publication date: Available online 23 December 2016
      Source:Alzheimer's & Dementia
      Author(s): Tharick A. Pascoal, Sulantha Mathotaarachchi, Monica Shin, Andrea L. Benedet, Sara Mohades, Seqian Wang, Tom Beaudry, Min Su Kang, Jean-Paul Soucy, Aurelie Labbe, Serge Gauthier, Pedro Rosa-Neto
      Introduction Recent literature proposes that amyloid-β and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia. Methods We stratified 314 mild cognitive impairment individuals using [18F]florbetapir positron emission tomography amyloid-β imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers. Results We found that the synergism between [18F]florbetapir and p-tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel-based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD. Discussion Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between amyloid-β and p-tau proteins.

      PubDate: 2016-12-28T19:33:07Z
      DOI: 10.1016/j.jalz.2016.06.115
       
  • Recommendations for CSF AD biomarkers in the diagnostic evaluation of MCI
    • Authors: Sanna-Kaisa Herukka; Anja Hviid Simonsen; Niels Andreasen; Ines Baldeiras; Maria Bjerke; Kaj Blennow; Sebastiaan Engelborghs; Giovanni B. Frisoni; Tomasz Gabryelewicz; Samantha Galluzzi; Ron Handels; Milica G. Kramberger; Agnieszka Kulczyńska; Jose Luis Molinuevo; Barbara Mroczko; Agneta Nordberg; Catarina Resende Oliveira; Markus Otto; Juha O. Rinne; Uroš Rot; Esen Saka; Hilkka Soininen; Hanne Struyfs; Silvia Suardi; Pieter Jelle Visser; Bengt Winblad; Henrik Zetterberg; Gunhild Waldemar
      Abstract: Publication date: Available online 27 October 2016
      Source:Alzheimer's & Dementia
      Author(s): Sanna-Kaisa Herukka, Anja Hviid Simonsen, Niels Andreasen, Ines Baldeiras, Maria Bjerke, Kaj Blennow, Sebastiaan Engelborghs, Giovanni B. Frisoni, Tomasz Gabryelewicz, Samantha Galluzzi, Ron Handels, Milica G. Kramberger, Agnieszka Kulczyńska, Jose Luis Molinuevo, Barbara Mroczko, Agneta Nordberg, Catarina Resende Oliveira, Markus Otto, Juha O. Rinne, Uroš Rot, Esen Saka, Hilkka Soininen, Hanne Struyfs, Silvia Suardi, Pieter Jelle Visser, Bengt Winblad, Henrik Zetterberg, Gunhild Waldemar
      This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1–42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling.

      PubDate: 2016-11-02T00:02:54Z
      DOI: 10.1016/j.jalz.2016.09.009
       
  • Blood-brain barrier failure as a core mechanism in cerebral small vessel
           disease and dementia: evidence from a cohort study
    • Authors: Joanna M. Wardlaw; Stephen Makin; Maria C. Valdés Hernández; Paul Armitage; Anna K. Heye; Francesca M. Chappell; Susana Muñoz-Maniega; Eleni Sakka; Kirsten Shuler; Martin S. Dennis; Michael J. Thrippleton
      Abstract: Publication date: Available online 27 October 2016
      Source:Alzheimer's & Dementia
      Author(s): Joanna M. Wardlaw, Stephen Makin, Maria C. Valdés Hernández, Paul Armitage, Anna K. Heye, Francesca M. Chappell, Susana Muñoz-Maniega, Eleni Sakka, Kirsten Shuler, Martin S. Dennis, Michael J. Thrippleton
      Introduction Small vessel disease (SVD) is a common contributor to dementia. Subtle blood-brain barrier (BBB) leakage may be important in SVD-induced brain damage. Methods We assessed imaging, clinical variables, and cognition in patients with mild (i.e., nondisabling) ischemic lacunar or cortical stroke. We analyzed BBB leakage, interstitial fluid, and white matter integrity using multimodal tissue-specific spatial analysis around white matter hyperintensities (WMH). We assessed predictors of 1 year cognition, recurrent stroke, and dependency. Results In 201 patients, median age 67 (range 34–97), BBB leakage, and interstitial fluid were higher in WMH than normal-appearing white matter; leakage in normal-appearing white matter increased with proximity to WMH (P < .0001), with WMH severity (P = .033), age (P = .03), and hypertension (P < .0001). BBB leakage in WMH predicted declining cognition at 1 year. Discussion BBB leakage increases in normal-appearing white matter with WMH and predicts worsening cognition. Interventions to reduce BBB leakage may prevent SVD-associated dementia.

      PubDate: 2016-11-02T00:02:54Z
      DOI: 10.1016/j.jalz.2016.09.006
       
  • Recommendations for CSF AD biomarkers in the diagnostic evaluation of
           dementia
    • Authors: Anja Hviid Simonsen; Sanna-Kaisa Herukka; Niels Andreasen; Ines Baldeiras; Maria Bjerke; Kaj Blennow; Sebastiaan Engelborghs; Giovanni B. Frisoni; Tomasz Gabryelewicz; Samantha Galluzzi; Ron Handels; Milica G. Kramberger; Agnieszka Kulczyńska; Jose Luis Molinuevo; Barbara Mroczko; Agneta Nordberg; Catarina Resende Oliveira; Markus Otto; Juha O. Rinne; Uroš Rot; Esen Saka; Hilkka Soininen; Hanne Struyfs; Silvia Suardi; Pieter Jelle Visser; Bengt Winblad; Henrik Zetterberg; Gunhild Waldemar
      Abstract: Publication date: Available online 27 October 2016
      Source:Alzheimer's & Dementia
      Author(s): Anja Hviid Simonsen, Sanna-Kaisa Herukka, Niels Andreasen, Ines Baldeiras, Maria Bjerke, Kaj Blennow, Sebastiaan Engelborghs, Giovanni B. Frisoni, Tomasz Gabryelewicz, Samantha Galluzzi, Ron Handels, Milica G. Kramberger, Agnieszka Kulczyńska, Jose Luis Molinuevo, Barbara Mroczko, Agneta Nordberg, Catarina Resende Oliveira, Markus Otto, Juha O. Rinne, Uroš Rot, Esen Saka, Hilkka Soininen, Hanne Struyfs, Silvia Suardi, Pieter Jelle Visser, Bengt Winblad, Henrik Zetterberg, Gunhild Waldemar
      This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1–42, tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results. The working group found sufficient evidence to support a recommendation to use CSF AD biomarkers as a supplement to clinical evaluation, particularly in uncertain and atypical cases, to identify or exclude AD as the cause of dementia. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Operational recommendations for the interpretation of ambiguous CSF biomarker results were also provided.

      PubDate: 2016-11-02T00:02:54Z
      DOI: 10.1016/j.jalz.2016.09.008
       
  • An investigation of cerebrovascular lesions in dementia with Lewy bodies
           compared to Alzheimer's disease
    • Authors: Lidia Sarro; Nirubol Tosakulwong; Christopher G. Schwarz; Jonathan Graff-Radford; Scott A. Przybelski; Timothy G. Lesnick; Samantha M. Zuk; Robert I. Reid; Mekala R. Raman; Bradley F. Boeve; Tanis J. Ferman; David S. Knopman; Giancarlo Comi; Massimo Filippi; Melissa E. Murray; Joseph E. Parisi; Dennis W. Dickson; Ronald C. Petersen; Clifford R. Jack; Kejal Kantarci
      Abstract: Publication date: Available online 10 August 2016
      Source:Alzheimer's & Dementia
      Author(s): Lidia Sarro, Nirubol Tosakulwong, Christopher G. Schwarz, Jonathan Graff-Radford, Scott A. Przybelski, Timothy G. Lesnick, Samantha M. Zuk, Robert I. Reid, Mekala R. Raman, Bradley F. Boeve, Tanis J. Ferman, David S. Knopman, Giancarlo Comi, Massimo Filippi, Melissa E. Murray, Joseph E. Parisi, Dennis W. Dickson, Ronald C. Petersen, Clifford R. Jack, Kejal Kantarci
      Introduction Cerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB). Methods White-matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age-matched and sex-matched cognitively normal subjects (CN) from a population-based cohort. Results DLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia. Discussion In DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.

      PubDate: 2016-10-26T14:48:35Z
      DOI: 10.1016/j.jalz.2016.07.003
       
  • Tract-specific white matter hyperintensities disrupt neural network
           function in Alzheimer's disease
    • Authors: Alexander N.W. Taylor; Lana Kambeitz-Ilankovic; Benno Gesierich; Lee Simon-Vermot; Nicolai Franzmeier; Miguel Á. Araque Caballero; Sophia Müller; Liu Hesheng; Birgit Ertl-Wagner; Katharina Bürger; Michael W. Weiner; Martin Dichgans; Marco Duering; Michael Ewers
      Abstract: Publication date: Available online 16 July 2016
      Source:Alzheimer's & Dementia
      Author(s): Alexander N.W. Taylor, Lana Kambeitz-Ilankovic, Benno Gesierich, Lee Simon-Vermot, Nicolai Franzmeier, Miguel Á. Araque Caballero, Sophia Müller, Liu Hesheng, Birgit Ertl-Wagner, Katharina Bürger, Michael W. Weiner, Martin Dichgans, Marco Duering, Michael Ewers
      Introduction White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. Method Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). Results WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. Conclusions High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function.

      PubDate: 2016-10-26T14:48:35Z
      DOI: 10.1016/j.jalz.2016.06.2358
       
  • Defining imaging biomarker cut points for brain aging and
           Alzheimer's disease
    • Authors: 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
      Abstract: Publication date: Available online 30 September 2016
      Source:Alzheimer's & Dementia
      Author(s): 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, 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 positive and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of clinically impaired versus age-matched CN method labeled fewer people positive. Discussion In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut-point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of clinically impaired versus young CN method and base conservative cut points on the accuracy of clinically impaired versus age-matched CN method.

      PubDate: 2016-10-03T13:45:08Z
      DOI: 10.1016/j.jalz.2016.08.005
       
 
 
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