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Showing 1 - 200 of 3120 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 8)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 26, 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: 30, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 378, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 26, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
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: 237, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
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   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
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: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
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Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 5)
Acute Pain     Full-text available via subscription   (Followers: 13)
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: 7, 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: 140, 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: 17, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
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: 4)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 9, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 12, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 23, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 26, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 6, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 4)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 13)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 26, 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: 9, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 12)
Advances in Digestive Medicine     Open Access   (Followers: 7)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 6)
Advances in Drug Research     Full-text available via subscription   (Followers: 23)
Advances in Ecological Research     Full-text available via subscription   (Followers: 47, 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: 9)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 46, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 52, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 17, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
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: 22, 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: 27)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, 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: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 10)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, 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: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 23)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 9, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
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: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, 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: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, 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: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 1.5, h-index: 62)
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: 371, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
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: 31, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 45, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 338, 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: 433, 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: 42, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 3)
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: 8)
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: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, 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: 49, 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: 5)
American Heart J.     Hybrid Journal   (Followers: 48, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 48, 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: 9, 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: 32, 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: 31, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 45, 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: 207, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 61, 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: 24, 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: 26, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 36, 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: 60, 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  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 36, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 173, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 12)
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  
Animal Behaviour     Hybrid Journal   (Followers: 176, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)

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Journal Cover Alzheimer's & Dementia
  [SJR: 4.289]   [H-I: 64]   [49 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1552-5260 - ISSN (Online) 1552-5279
   Published by Elsevier Homepage  [3123 journals]
  • Dental care utilization in patients with different types of dementia:
           A longitudinal nationwide study of 58,037 individuals
    • Authors: Seyed-Mohammad Fereshtehnejad; Sara Garcia-Ptacek; Dorota Religa; Jacob Holmer; Kåre Buhlin; Maria Eriksdotter; Gunilla Sandborgh-Englund
      Pages: 10 - 19
      Abstract: Publication date: January 2018
      Source:Alzheimer's & Dementia, Volume 14, Issue 1
      Author(s): Seyed-Mohammad Fereshtehnejad, Sara Garcia-Ptacek, Dorota Religa, Jacob Holmer, Kåre Buhlin, Maria Eriksdotter, Gunilla Sandborgh-Englund
      Introduction Dementia may be associated with discontinuation of regular dental checkups, which in turn results in poorer oral health. Methods We investigated the trend of change in dental care utilization and the number of teeth before and after being diagnosed with dementia. Longitudinal cognitive- and dental health-related information were merged using data on 58,037 newly diagnosed individuals from the Swedish Dementia Registry and Swedish Dental Health Register during 2007 to 2015. Results Following dementia diagnosis, rate of dental care visits significantly declined. Individuals with mixed dementia, dementia with parkinsonism, and those with more severe and faster cognitive impairment had significantly higher rate of decline in dental care utilization. Vascular dementia and lower baseline Mini–Mental State Examination score were significant predictors of faster loss of teeth. Discussion Dental care utilization markedly declines following dementia diagnosis. The reduction is more prominent in those with rapid progressive cognitive impairment and the ones with extra frailty burden.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2017.05.004
  • Predictors of emergency department attendance by people with dementia in
           their last year of life: Retrospective cohort study using linked clinical
           and administrative data
    • Authors: Katherine E. Sleeman; Gayan Perera; Robert Stewart; Irene J. Higginson
      Pages: 20 - 27
      Abstract: Publication date: January 2018
      Source:Alzheimer's & Dementia, Volume 14, Issue 1
      Author(s): Katherine E. Sleeman, Gayan Perera, Robert Stewart, Irene J. Higginson
      Introduction A fall in hospital deaths in dementia has been interpreted as indicating an improvement in end-of-life care. Whether other indicators of quality of end-of-life care, such as emergency department (ED) attendance, show a similar trend is unclear. Methods Retrospective cohort study using electronic medical records from a large mental health care provider, linked to national mortality and hospital use data (2008–2013). Results Of 4867 patients, 78.6% (3824) had at least one ED attendance during their last year of life (mean 2.13, standard deviation 2.34, range 0–54). ED attendance increased over the time period (incidence rate ratio 1.62, 95% confidence interval 1.46–1.80 for 2012–2013 compared with 2008–2009). Discussion ED attendance in the last year of life for people with dementia is common and is increasing. Policy makers must pay attention to a broader range of indicators of poor end-of-life care alongside the place of death.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2017.06.2267
  • Association of blood lipids with Alzheimer's disease:
           A comprehensive lipidomics analysis
    • Authors: Petroula Proitsi; Min Kim; Luke Whiley; Andrew Simmons; Martina Sattlecker; Latha Velayudhan; Michelle K. Lupton; Hillka Soininen; Iwona Kloszewska; Patrizia Mecocci; Magda Tsolaki; Bruno Vellas; Simon Lovestone; John F. Powell; Richard J.B. Dobson; Cristina Legido-Quigley
      Pages: 140 - 151
      Abstract: Publication date: February 2017
      Source:Alzheimer's & Dementia, Volume 13, Issue 2
      Author(s): Petroula Proitsi, Min Kim, Luke Whiley, Andrew Simmons, Martina Sattlecker, Latha Velayudhan, Michelle K. Lupton, Hillka Soininen, Iwona Kloszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Simon Lovestone, John F. Powell, Richard J.B. Dobson, Cristina Legido-Quigley
      Introduction The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex). Methods We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods. Results We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R2 = 0.10, test data set) and brain atrophy (R2 ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines. Discussion Blood lipids are promising AD biomarkers that may lead to new treatment strategies.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.08.003
  • The worldwide costs of dementia 2015 and comparisons with 2010
    • Authors: Anders Wimo; Maëlenn Guerchet; Gemma-Claire Ali; Yu-Tzu Wu; A. Matthew Prina; Bengt Winblad; Linus Jönsson; Zhaorui Liu; Martin Prince
      Pages: 1 - 7
      Abstract: Publication date: January 2017
      Source:Alzheimer's & Dementia, Volume 13, Issue 1
      Author(s): Anders Wimo, Maëlenn Guerchet, Gemma-Claire Ali, Yu-Tzu Wu, A. Matthew Prina, Bengt Winblad, Linus Jönsson, Zhaorui Liu, Martin Prince
      Introduction In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates. Methods This is a societal, prevalence-based global COI study. Results The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries. Costs of informal care and the direct costs of social care still contribute similar proportions of total costs, whereas the costs in the medical sector are much lower. The threshold of US $1 trillion will be crossed by 2018. Discussion Worldwide costs of dementia are enormous and still inequitably distributed. The increase in costs arises from increases in numbers of people with dementia and in increases in per person costs.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.07.150
  • The validity of the Memory Alteration Test and the Test Your Memory test
           for community-based identification of amnestic mild cognitive impairment
    • Authors: Seline Ozer; Krist Noonan; Melanie Burke; John Young; Sally Barber; Anne Forster; Roy Jones
      Pages: 987 - 995
      Abstract: Publication date: September 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 9
      Author(s): Seline Ozer, Krist Noonan, Melanie Burke, John Young, Sally Barber, Anne Forster, Roy Jones
      Introduction This study investigated the validity of two brief cognitive tests (Memory Alteration Test [M@T] and Test Your Memory [TYM] test) for identifying people with aMCI in the community. Methods Older people were invited to participate by their general practitioner practice. Eligible participants were assessed for aMCI using an operationalized approach to the Petersen criteria and the M@T and TYM. Results Both tests demonstrated significant ability in discriminating between people with aMCI and controls (AUC = 0.91 for M@T and 0.80 for TYM [P < .001 for both]). M@T performed with higher sensitivity than TYM (85% vs. 63%) and similar specificity (84% vs. 87%). Both tests demonstrated moderate test-retest reliability (κ = ∼0.5) and took <10 minutes to administer. Discussion M@T and TYM are quick to administer. M@T demonstrated higher diagnostic test accuracy than TYM and could provide an efficient method for identifying aMCI in clinical and research settings.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.03.014
  • Big data to smart data in Alzheimer's disease: The brain health modeling
           initiative to foster actionable knowledge
    • Authors: Hugo Geerts; Penny A. Dacks; Viswanath Devanarayan; Magali Haas; Zaven S. Khachaturian; Mark Forrest Gordon; Stuart Maudsley; Klaus Romero; Diane Stephenson
      Pages: 1014 - 1021
      Abstract: Publication date: September 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 9
      Author(s): Hugo Geerts, Penny A. Dacks, Viswanath Devanarayan, Magali Haas, Zaven S. Khachaturian, Mark Forrest Gordon, Stuart Maudsley, Klaus Romero, Diane Stephenson
      Massive investment and technological advances in the collection of extensive and longitudinal information on thousands of Alzheimer patients results in large amounts of data. These “big-data” databases can potentially advance CNS research and drug development. However, although necessary, they are not sufficient, and we posit that they must be matched with analytical methods that go beyond retrospective data-driven associations with various clinical phenotypes. Although these empirically derived associations can generate novel and useful hypotheses, they need to be organically integrated in a quantitative understanding of the pathology that can be actionable for drug discovery and development. We argue that mechanism-based modeling and simulation approaches, where existing domain knowledge is formally integrated using complexity science and quantitative systems pharmacology can be combined with data-driven analytics to generate predictive actionable knowledge for drug discovery programs, target validation, and optimization of clinical development.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.04.008
  • Big data to smart data in Alzheimer's disease: Real-world examples of
           advanced modeling and simulation
    • Authors: Magali Haas; Diane Stephenson; Klaus Romero; Mark Forrest Gordon; Neta Zach; Hugo Geerts
      Pages: 1022 - 1030
      Abstract: Publication date: September 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 9
      Author(s): Magali Haas, Diane Stephenson, Klaus Romero, Mark Forrest Gordon, Neta Zach, Hugo Geerts
      Many disease-modifying clinical development programs in Alzheimer's disease (AD) have failed to date, and development of new and advanced preclinical models that generate actionable knowledge is desperately needed. This review reports on computer-based modeling and simulation approach as a powerful tool in AD research. Statistical data-analysis techniques can identify associations between certain data and phenotypes, such as diagnosis or disease progression. Other approaches integrate domain expertise in a formalized mathematical way to understand how specific components of pathology integrate into complex brain networks. Private-public partnerships focused on data sharing, causal inference and pathway-based analysis, crowdsourcing, and mechanism-based quantitative systems modeling represent successful real-world modeling examples with substantial impact on CNS diseases. Similar to other disease indications, successful real-world examples of advanced simulation can generate actionable support of drug discovery and development in AD, illustrating the value that can be generated for different stakeholders.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.05.005
  • Alzheimer's disease risk variants modulate endophenotypes in mild
           cognitive impairment
    • Authors: Eva Louwersheimer; Steffen Wolfsgruber; Ana Espinosa; André Lacour; Stefanie Heilmann-Heimbach; Montserrat Alegret; Isabel Hernández; Maitée Rosende-Roca; Lluís Tárraga; Mercè Boada; Johannes Kornhuber; Oliver Peters; Lutz Frölich; Michael Hüll; Eckart Rüther; Jens Wiltfang; Martin Scherer; Steffi Riedel-Heller; Frank Jessen; Markus M. Nöthen; Wolfgang Maier; Ted Koene; Philip Scheltens; Henne Holstege; Michael Wagner; Agustín Ruiz; Wiesje M. van der Flier; Tim Becker; Alfredo Ramirez
      Pages: 872 - 881
      Abstract: Publication date: August 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 8
      Author(s): Eva Louwersheimer, Steffen Wolfsgruber, Ana Espinosa, André Lacour, Stefanie Heilmann-Heimbach, Montserrat Alegret, Isabel Hernández, Maitée Rosende-Roca, Lluís Tárraga, Mercè Boada, Johannes Kornhuber, Oliver Peters, Lutz Frölich, Michael Hüll, Eckart Rüther, Jens Wiltfang, Martin Scherer, Steffi Riedel-Heller, Frank Jessen, Markus M. Nöthen, Wolfgang Maier, Ted Koene, Philip Scheltens, Henne Holstege, Michael Wagner, Agustín Ruiz, Wiesje M. van der Flier, Tim Becker, Alfredo Ramirez
      Introduction We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI). Methods We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (aβ, tau, ptau). Results PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β ± SE:−0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10−4; ptau: 1.40 ± 0.36, P = 1.02 × 10−4). Discussion In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.01.006
  • Predicting the progression of Alzheimer's disease dementia:
           A multidomain health policy model
    • Authors: Colin Green; Shenqiu Zhang
      Pages: 776 - 785
      Abstract: Publication date: July 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 7
      Author(s): Colin Green, Shenqiu Zhang
      Introduction We develop a multidomain model to predict progression of Alzheimer's disease dementia (AD). Methods Data from the US National Alzheimer's Coordinating Center (n = 3009) are used to examine change in symptom status and to estimate transition probabilities between health states described using cognitive function, functional ability, and behavior. A model is used to predict progression and to assess a hypothetical treatment scenario that slows mild to moderate AD progression. Results More than 70% of participants moved state over 12 months. The majority moved in domains other than cognitive function. Over 5 years, of those alive more than half are in severe AD health states. Assessing an intervention scenario, we see fewer years in more severe health states and a potential impact (life years saved) due to mortality improvements. Discussion The model developed is exploratory and has limitations but illustrates the importance of using a multidomain approach when assessing impacts of AD and interventions.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.01.011
  • Meta-analysis of synaptic pathology in Alzheimer's disease reveals
           selective molecular vesicular machinery vulnerability
    • Authors: Martijn C. de Wilde; Cassia R. Overk; John W. Sijben; Eliezer Masliah
      Pages: 633 - 644
      Abstract: Publication date: June 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 6
      Author(s): Martijn C. de Wilde, Cassia R. Overk, John W. Sijben, Eliezer Masliah
      Introduction Loss of synapses best correlates to cognitive deficits in Alzheimer's disease (AD) in which oligomeric neurotoxic species of amyloid-β appears to contribute synaptic pathology. Although a number of clinical pathologic studies have been performed with limited sample size, there are no systematic studies encompassing large samples. Therefore, we performed a meta-analysis study. Methods We identified 417 publications reporting postmortem synapse and synaptic marker loss from AD patients. Two meta-analyses were performed using a single database of subselected publications and calculating the standard mean differences. Results Meta-analysis confirmed synaptic loss in selected brain regions is an early event in AD pathogenesis. The second meta-analysis of 57 synaptic markers revealed that presynaptic makers were affected more than postsynaptic markers. Discussion The present meta-analysis study showed a consistent synaptic loss across brain regions and that molecular machinery including endosomal pathways, vesicular assembly mechanisms, glutamate receptors, and axonal transport are often affected.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2015.12.005
  • Crowdsourced estimation of cognitive decline and resilience in Alzheimer's
    • Authors: Genevera I. Allen; Nicola Amoroso; Catalina Anghel; Venkat Balagurusamy; Christopher J. Bare; Derek Beaton; Roberto Bellotti; David A. Bennett; Kevin L. Boehme; Paul C. Boutros; Laura Caberlotto; Cristian Caloian; Frederick Campbell; Elias Chaibub Neto; Yu-Chuan Chang; Beibei Chen; Chien-Yu Chen; Ting-Ying Chien; Tim Clark; Sudeshna Das; Christos Davatzikos; Jieyao Deng; Donna Dillenberger; Richard J.B. Dobson; Qilin Dong; Jimit Doshi; Denise Duma; Rosangela Errico; Guray Erus; Evan Everett; David W. Fardo; Stephen H. Friend; Holger Fröhlich; Jessica Gan; Peter St George-Hyslop; Satrajit S. Ghosh; Enrico Glaab; Robert C. Green; Yuanfang Guan; Ming-Yi Hong; Chao Huang; Jinseub Hwang; Joseph Ibrahim; Paolo Inglese; Anandhi Iyappan; Qijia Jiang; Yuriko Katsumata; John S.K. Kauwe; Arno Klein; Dehan Kong; Roland Krause; Emilie Lalonde; Mario Lauria; Eunjee Lee; Xihui Lin; Zhandong Liu; Julie Livingstone; Benjamin A. Logsdon; Simon Lovestone; Tsung-wei Ma; Ashutosh Malhotra; Lara M. Mangravite; Taylor J. Maxwell; Emily Merrill; John Nagorski; Aishwarya Namasivayam; Manjari Narayan; Mufassra Naz; Stephen J. Newhouse; Thea C. Norman; Ramil N. Nurtdinov; Yen-Jen Oyang; Yudi Pawitan; Shengwen Peng; Mette A. Peters; Stephen R. Piccolo; Paurush Praveen; Corrado Priami; Veronica Y. Sabelnykova; Philipp Senger; Xia Shen; Andrew Simmons; Aristeidis Sotiras; Gustavo Stolovitzky; Sabina Tangaro; Andrea Tateo; Yi-An Tung; Nicholas J. Tustison; Erdem Varol; George Vradenburg; Michael W. Weiner; Guanghua Xiao; Lei Xie; Yang Xie; Jia Xu; Hojin Yang; Xiaowei Zhan; Yunyun Zhou; Fan Zhu; Hongtu Zhu; Shanfeng Zhu
      Pages: 645 - 653
      Abstract: Publication date: June 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 6
      Author(s): Genevera I. Allen, Nicola Amoroso, Catalina Anghel, Venkat Balagurusamy, Christopher J. Bare, Derek Beaton, Roberto Bellotti, David A. Bennett, Kevin L. Boehme, Paul C. Boutros, Laura Caberlotto, Cristian Caloian, Frederick Campbell, Elias Chaibub Neto, Yu-Chuan Chang, Beibei Chen, Chien-Yu Chen, Ting-Ying Chien, Tim Clark, Sudeshna Das, Christos Davatzikos, Jieyao Deng, Donna Dillenberger, Richard J.B. Dobson, Qilin Dong, Jimit Doshi, Denise Duma, Rosangela Errico, Guray Erus, Evan Everett, David W. Fardo, Stephen H. Friend, Holger Fröhlich, Jessica Gan, Peter St George-Hyslop, Satrajit S. Ghosh, Enrico Glaab, Robert C. Green, Yuanfang Guan, Ming-Yi Hong, Chao Huang, Jinseub Hwang, Joseph Ibrahim, Paolo Inglese, Anandhi Iyappan, Qijia Jiang, Yuriko Katsumata, John S.K. Kauwe, Arno Klein, Dehan Kong, Roland Krause, Emilie Lalonde, Mario Lauria, Eunjee Lee, Xihui Lin, Zhandong Liu, Julie Livingstone, Benjamin A. Logsdon, Simon Lovestone, Tsung-wei Ma, Ashutosh Malhotra, Lara M. Mangravite, Taylor J. Maxwell, Emily Merrill, John Nagorski, Aishwarya Namasivayam, Manjari Narayan, Mufassra Naz, Stephen J. Newhouse, Thea C. Norman, Ramil N. Nurtdinov, Yen-Jen Oyang, Yudi Pawitan, Shengwen Peng, Mette A. Peters, Stephen R. Piccolo, Paurush Praveen, Corrado Priami, Veronica Y. Sabelnykova, Philipp Senger, Xia Shen, Andrew Simmons, Aristeidis Sotiras, Gustavo Stolovitzky, Sabina Tangaro, Andrea Tateo, Yi-An Tung, Nicholas J. Tustison, Erdem Varol, George Vradenburg, Michael W. Weiner, Guanghua Xiao, Lei Xie, Yang Xie, Jia Xu, Hojin Yang, Xiaowei Zhan, Yunyun Zhou, Fan Zhu, Hongtu Zhu, Shanfeng Zhu
      Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.02.006
  • Understanding the genetics of APOE and TOMM40 and role of mitochondrial
           structure and function in clinical pharmacology of Alzheimer's disease
    • Authors: Allen Roses; Scott Sundseth; Ann Saunders; William Gottschalk; Dan Burns; Michael Lutz
      Pages: 687 - 694
      Abstract: Publication date: June 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 6
      Author(s): Allen Roses, Scott Sundseth, Ann Saunders, William Gottschalk, Dan Burns, Michael Lutz
      The methodology of Genome-Wide Association Screening (GWAS) has been applied for more than a decade. Translation to clinical utility has been limited, especially in Alzheimer's Disease (AD). It has become standard practice in the analyses of more than two dozen AD GWAS studies to exclude the apolipoprotein E (APOE) region because of its extraordinary statistical support, unique thus far in complex human diseases. New genes associated with AD are proposed frequently based on SNPs associated with odds ratio (OR) < 1.2. Most of these SNPs are not located within the associated gene exons or introns but are located variable distances away. Often pathologic hypotheses for these genes are presented, with little or no experimental support. By eliminating the analyses of the APOE-TOMM40 linkage disequilibrium region, the relationship and data of several genes that are co-located in that LD region have been largely ignored. Early negative interpretations limited the interest of understanding the genetic data derived from GWAS, particularly regarding the TOMM40 gene. This commentary describes the history and problem(s) in interpretation of the genetic interrogation of the “APOE” region and provides insight into a metabolic mitochondrial basis for the etiology of AD using both APOE and TOMM40 genetics.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.03.015
  • Information and communication technology solutions for outdoor navigation
           in dementia
    • Authors: Stefan Teipel; Claudio Babiloni; Jesse Hoey; Jeffrey Kaye; Thomas Kirste; Oliver K. Burmeister
      Pages: 695 - 707
      Abstract: Publication date: June 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 6
      Author(s): Stefan Teipel, Claudio Babiloni, Jesse Hoey, Jeffrey Kaye, Thomas Kirste, Oliver K. Burmeister
      Introduction Information and communication technology (ICT) is potentially mature enough to empower outdoor and social activities in dementia. However, actual ICT-based devices have limited functionality and impact, mainly limited to safety. What is an ideal operational framework to enhance this field to support outdoor and social activities' Methods Review of literature and cross-disciplinary expert discussion. Results A situation-aware ICT requires a flexible fine-tuning by stakeholders of system usability and complexity of function, and of user safety and autonomy. It should operate by artificial intelligence/machine learning and should reflect harmonized stakeholder values, social context, and user residual cognitive functions. ICT services should be proposed at the prodromal stage of dementia and should be carefully validated within the life space of users in terms of quality of life, social activities, and costs. Discussion The operational framework has the potential to produce ICT and services with high clinical impact but requires substantial investment.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2015.11.003
  • Molecular genetics of early-onset Alzheimer's disease revisited
    • Authors: Rita Cacace; Kristel Sleegers; Christine Van Broeckhoven
      Pages: 733 - 748
      Abstract: Publication date: June 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 6
      Author(s): Rita Cacace, Kristel Sleegers, Christine Van Broeckhoven
      As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.01.012
  • Technical performance of a novel, fully automated electrochemiluminescence
           immunoassay for the quantitation of β-amyloid (1–42) in human
           cerebrospinal fluid
    • Authors: Tobias Bittner; Henrik Zetterberg; Charlotte E. Teunissen; Richard E. Ostlund; Michael Militello; Ulf Andreasson; Isabelle Hubeek; David Gibson; David C. Chu; Udo Eichenlaub; Peter Heiss; Uwe Kobold; Andreas Leinenbach; Kairat Madin; Ekaterina Manuilova; Christina Rabe; Kaj Blennow
      Pages: 517 - 526
      Abstract: Publication date: May 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 5
      Author(s): Tobias Bittner, Henrik Zetterberg, Charlotte E. Teunissen, Richard E. Ostlund, Michael Militello, Ulf Andreasson, Isabelle Hubeek, David Gibson, David C. Chu, Udo Eichenlaub, Peter Heiss, Uwe Kobold, Andreas Leinenbach, Kairat Madin, Ekaterina Manuilova, Christina Rabe, Kaj Blennow
      Introduction Available assays for quantitation of the Alzheimer's disease (AD) biomarker amyloid-beta 1–42 (Aβ [1–42]) in cerebrospinal fluid demonstrate significant variability and lack of standardization to reference measurement procedures (RMPs). We report analytical performance data for the novel Elecsys β-amyloid (1–42) assay (Roche Diagnostics). Methods Lot-to-lot comparability was tested using method comparison. Performance parameters were measured according to Clinical & Laboratory Standards Institute (CLSI) guidelines. The assay was standardized to a Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved RMP. Results Limit of quantitation was <11.28 pg/mL, and the assay was linear throughout the measuring range (200–1700 pg/mL). Excellent lot-to-lot comparability was observed (correlation coefficients [Pearson's r] >0.995; bias in medical decision area <2%). Repeatability coefficients of variation (CVs) were 1.0%–1.6%, intermediate CVs were 1.9%–4.0%, and intermodule CVs were 1.1%–3.9%. Estimated total reproducibility was 2.0%–5.1%. Correlation with the RMP was good (Pearson's r, 0.93). Discussion The Elecsys β-amyloid (1–42) assay has high analytical performance that may improve biomarker-based AD diagnosis.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2015.09.009
  • The pattern of amyloid accumulation in the brains of adults with Down
    • Authors: Tiina Annus; Liam R. Wilson; Young T. Hong; Julio Acosta–Cabronero; Tim D. Fryer; Arturo Cardenas–Blanco; Robert Smith; Istvan Boros; Jonathan P. Coles; Franklin I. Aigbirhio; David K. Menon; Shahid H. Zaman; Peter J. Nestor; Anthony J. Holland
      Pages: 538 - 545
      Abstract: Publication date: May 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 5
      Author(s): Tiina Annus, Liam R. Wilson, Young T. Hong, Julio Acosta–Cabronero, Tim D. Fryer, Arturo Cardenas–Blanco, Robert Smith, Istvan Boros, Jonathan P. Coles, Franklin I. Aigbirhio, David K. Menon, Shahid H. Zaman, Peter J. Nestor, Anthony J. Holland
      Introduction Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. Methods Forty-nine adults with DS aged 25–65 underwent positron emission tomography with Pittsburgh compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. Results Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. Discussion PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2015.07.490
  • Ethical challenges in preclinical Alzheimer's disease observational
           studies and trials: Results of the Barcelona summit
    • Authors: José L. Molinuevo; Jordi Cami; Xavier Carné; Maria C. Carrillo; Jean Georges; Maria B. Isaac; Zaven Khachaturian; Scott Y.H. Kim; John C. Morris; Florence Pasquier; Craig Ritchie; Reisa Sperling; Jason Karlawish
      Pages: 614 - 622
      Abstract: Publication date: May 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 5
      Author(s): José L. Molinuevo, Jordi Cami, Xavier Carné, Maria C. Carrillo, Jean Georges, Maria B. Isaac, Zaven Khachaturian, Scott Y.H. Kim, John C. Morris, Florence Pasquier, Craig Ritchie, Reisa Sperling, Jason Karlawish
      Alzheimer's disease (AD) is among the most significant health care burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals' biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants, and disclose or not biomarker status with attention to study type (observational studies vs clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.01.009
  • Report on milestones for care and support under the U.S. National Plan to
           Address Alzheimer's Disease
    • Authors: Soo Borson; Malaz A. Boustani; Kathleen C. Buckwalter; Louis D. Burgio; Joshua Chodosh; Richard H. Fortinsky; David R. Gifford; Lisa P. Gwyther; Mary Jane Koren; Joanne Lynn; Cheryl Phillips; Martha Roherty; Judah Ronch; Claudia Stahl; Lauren Rodgers; Hye Kim; Matthew Baumgart; Angela Geiger
      Pages: 334 - 369
      Abstract: Publication date: March 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 3
      Author(s): Soo Borson, Malaz A. Boustani, Kathleen C. Buckwalter, Louis D. Burgio, Joshua Chodosh, Richard H. Fortinsky, David R. Gifford, Lisa P. Gwyther, Mary Jane Koren, Joanne Lynn, Cheryl Phillips, Martha Roherty, Judah Ronch, Claudia Stahl, Lauren Rodgers, Hye Kim, Matthew Baumgart, Angela Geiger
      Introduction Under the U.S. national Alzheimer's plan, the National Institutes of Health identified milestones required to meet the plan's biomedical research goal (Goal 1). However, similar milestones have not been created for the goals on care (Goal 2) and support (Goal 3). Methods The Alzheimer's Association convened a workgroup with expertise in clinical care, long-term services and supports, dementia care and support research, and public policy. The workgroup reviewed the literature on Alzheimer's care and support; reviewed how other countries are addressing the issue; and identified public policies needed over the next 10 years to achieve a more ideal care and support system. Results The workgroup developed and recommended 73 milestones for Goal 2 and 56 milestones for Goal 3. Discussion To advance the implementation of the U.S. national Alzheimer's plan, the U.S. government should adopt these recommended milestones, or develop similar milestones, to be incorporated into the national plan.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.01.005
  • Prudent diet may attenuate the adverse effects of Western diet on
           cognitive decline
    • Authors: Behnaz Shakersain; Giola Santoni; Susanna C. Larsson; Gerd Faxén-Irving; Johan Fastbom; Laura Fratiglioni; Weili Xu
      Pages: 100 - 109
      Abstract: Publication date: February 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 2
      Author(s): Behnaz Shakersain, Giola Santoni, Susanna C. Larsson, Gerd Faxén-Irving, Johan Fastbom, Laura Fratiglioni, Weili Xu
      Introduction The influence of mixed dietary patterns on cognitive changes is unknown. Methods A total of 2223 dementia-free participants aged ≥60 were followed up for 6 years to examine the impact of dietary patterns on cognitive decline. Mini-mental state examination (MMSE) was administered. Diet was assessed by a food frequency questionnaire. By factor analysis, Western and prudent dietary patterns emerged. Mixed-effect models for longitudinal data with repeated measurements were used. Results Compared with the lowest adherence to each pattern, the highest adherence to prudent pattern was related to less MMSE decline (β = 0.106, P = .011), whereas the highest adherence to Western pattern was associated with more MMSE decline (β = −0.156, P < .001). The decline associated with Western diet was attenuated when accompanied by high adherence to prudent pattern. Discussion High adherence to prudent diet may diminish the adverse effects of high adherence to Western diet on cognitive decline.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2015.08.002
  • Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease
    • Authors: Eric R. Siemers; Karen L. Sundell; Christopher Carlson; Michael Case; Gopalan Sethuraman; Hong Liu-Seifert; Sherie A. Dowsett; Michael J. Pontecorvo; Robert A. Dean; Ronald Demattos
      Pages: 110 - 120
      Abstract: Publication date: February 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 2
      Author(s): Eric R. Siemers, Karen L. Sundell, Christopher Carlson, Michael Case, Gopalan Sethuraman, Hong Liu-Seifert, Sherie A. Dowsett, Michael J. Pontecorvo, Robert A. Dean, Ronald Demattos
      Introduction EXPEDITION and EXPEDITION2 were identically designed placebo-controlled phase 3 studies assessing effects of solanezumab, an antiamyloid monoclonal antibody binding soluble amyloid-β peptide, on cognitive and functional decline over 80 weeks in patients with mild-to-moderate Alzheimer's disease (AD). Primary findings for both studies have been published. Methods Secondary analyses of efficacy, biomarker, and safety endpoints in the pooled (EXPEDTION + EXPEDITION2) mild AD population were performed. Results In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study–Activities of Daily Living functional scale Instrumental ADLs. Baseline-to-endpoint changes did not differ between treatment groups for Alzheimer's Disease Cooperative Study–Activities of Daily Living functional scale, basic items of the ADCS-ADL, and Clinical Dementia Rating Sum of Boxes. Plasma/cerebrospinal fluid biomarker findings indicated target engagement by solanezumab. Solanezumab demonstrated acceptable safety. Efficacy findings for the moderate AD population are also provided. Discussion These findings describe solanezumab effects on efficacy/safety measures in a mild AD population. Another phase 3 study, EXPEDITION3, will investigate solanezumab's effects in a mild AD population.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2015.06.1893
  • Kallikrein-8 inhibition attenuates Alzheimer's disease pathology in mice
    • Authors: Arne Herring; Yvonne Münster; Tamer Akkaya; Sahar Moghaddam; Katharina Deinsberger; Jakob Meyer; Julia Zahel; Eduardo Sanchez-Mendoza; Yachao Wang; Dirk M. Hermann; Thomas Arzberger; Sarah Teuber-Hanselmann; Kathy Keyvani
      Pages: 1273 - 1287
      Abstract: Publication date: December 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 12
      Author(s): Arne Herring, Yvonne Münster, Tamer Akkaya, Sahar Moghaddam, Katharina Deinsberger, Jakob Meyer, Julia Zahel, Eduardo Sanchez-Mendoza, Yachao Wang, Dirk M. Hermann, Thomas Arzberger, Sarah Teuber-Hanselmann, Kathy Keyvani
      Introduction Memory loss and increased anxiety are clinical hallmarks of Alzheimer's disease (AD). Kallikrein-8 is a protease implicated in memory acquisition and anxiety, and its mRNA is known to be up-regulated in AD-affected human hippocampus. Therefore, an involvement of Kallikrein-8 in Alzheimer's pathogenesis is conceivable but remains to be proved. Methods We determined the cerebral expression of Kallikrein-8 mRNA and protein during the course of AD in patients and in transgenic mice and tested the impact of Kallikrein-8 inhibition on AD-related pathology in mice and in primary glial cells. Results Kallikrein-8 mRNA and protein were up-regulated in both species at incipient stages of AD. Kallikrein-8 inhibition impeded amyloidogenic amyloid-precursor-protein processing, facilitated amyloid β (Aβ) clearance across the blood-brain-barrier, boosted autophagy, reduced Aβ load and tau pathology, enhanced neuroplasticity, reversed molecular signatures of anxiety, and ultimately improved memory and reduced fear. Discussion Kallikrein-8 is a promising new therapeutic target against AD.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2016.05.006
  • CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's
    • 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
  • Obesity trajectories and risk of dementia: 28 years of follow-up in the
           Whitehall II Study
    • Authors: Archana Singh-Manoux; Aline Dugravot; Martin Shipley; Eric J. Brunner; Alexis Elbaz; Séverine Sabia; Mika Kivimaki
      Abstract: Publication date: Available online 21 September 2017
      Source:Alzheimer's & Dementia
      Author(s): Archana Singh-Manoux, Aline Dugravot, Martin Shipley, Eric J. Brunner, Alexis Elbaz, Séverine Sabia, Mika Kivimaki
      Introduction We examined whether obesity at ages 50, 60, and 70 years is associated with subsequent dementia. Changes in body mass index (BMI) for more than 28 years before dementia diagnosis were compared with changes in BMI in those free of dementia. Methods A total of 10,308 adults (33% women) aged 35 to 55 years in 1985 were followed up until 2015. BMI was assessed six times and 329 cases of dementia were recorded. Results Obesity (BMI ≥30 kg/m2) at age 50 years (hazard ratio = 1.93; 1.35–2.75) but not at 60 or 70 years was associated with risk of dementia. Trajectories of BMI differed in those with dementia compared with all others (P < .0001) or to matched control subjects (P < .0001) such that BMI in dementia cases was higher from 28 years (P = .001) to 16 years (P = .05) and lower starting 8 years before diagnosis. Discussion Obesity in midlife and weight loss in the preclinical phase characterizes dementia; the current obesity epidemic may affect future dementia rates.

      PubDate: 2018-01-04T22:23:38Z
      DOI: 10.1016/j.jalz.2017.06.2637
  • METACOHORTS for the study of vascular disease and its contribution to
           cognitive decline and neurodegeneration: An initiative of the Joint
           Programme for Neurodegenerative Disease Research
    • Authors: METACOHORTS ConsortiumMartinDichgansJoannaWardlawEricSmithVeraZietemannSudhaSeshadriPerminderSachdevGeert; JanBiesselsFranzFazekasOscarBenaventeLeonardoPantoniFrank-ErikDe E.BlackCarolBrayneHuguesChabriatCharlotteCordonnierFergusDoubalEmrahDuzelMichaelEwersRichardFrayneVladimirHachinskiMohammad ArfanIkramFrankJessenEricJouventJenniferLinnJohnOBrienRobertvan OostenbruggeRainerMalikBernardMazoyerReinholdSchmidtLuciano A.SposatoBlossomStephanRichard H.SwartzMeikeVernooijAnandViswanathanDavidWerringKojiAbeLouiseAllanFrancescoArbaon behalf theVISTA
      Abstract: Publication date: December 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 12
      Author(s): METACOHORTS ConsortiumMartinDichgansJoannaWardlawEricSmithVeraZietemannSudhaSeshadriPerminderSachdevGeert JanBiesselsFranzFazekasOscarBenaventeLeonardoPantoniFrank-ErikDe LeeuwBoNorrvingPaulMatthewsChristopherChenVincentMokMarcoDüringWillWhiteleyKirstenShulerAlvaroAlonsoSandra E.BlackCarolBrayneHuguesChabriatCharlotteCordonnierFergusDoubalEmrahDuzelMichaelEwersRichardFrayneVladimirHachinskiMohammad ArfanIkramFrankJessenEricJouventJenniferLinnJohnO'BrienRobertvan OostenbruggeRainerMalikBernardMazoyerReinholdSchmidtLuciano A.SposatoBlossomStephanRichard H.SwartzMeikeVernooijAnandViswanathanDavidWerringKojiAbeLouiseAllanFrancescoArbaon behalf of theVISTA CollaborationH.-C.DienerS.DavisG.HankeyK.R.LeesB.OvbiageleC.WeirHee-JoonBaePhilip MW.BathRegisBordetMoniqueBretelerSeongChoiIanDearyCharlesDeCarliKlausEbmeierLeiFengSteven M.GreenbergMasafumiIharaRajeshKalariaSanYunKimJae-SungLimRichard I.LindleyGillianMeadAlisonMurrayTerryQuinnCraigRitchieRalphSaccoRustamAl-Shahi SalmanNikolaSpriggCathieSudlowAlanThomasMartinvan BoxtelJeroenvan der GrondAadvan der LugtYuan-HanYangCorresponding author. Tel.: +44-131-465-9570
      Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

      PubDate: 2018-01-04T22:23:38Z
  • Genetic risk factors for the posterior cortical atrophy variant of
           Alzheimer's disease
    • Authors: Jonathan Schott; Sebastian Crutch Minerva Carrasquillo James Uphill Tim Shakespeare
      Abstract: Publication date: August 2016
      Source:Alzheimer's & Dementia, Volume 12, Issue 8
      Author(s): Jonathan M. Schott, Sebastian J. Crutch, Minerva M. Carrasquillo, James Uphill, Tim J. Shakespeare, Natalie S. Ryan, Keir X. Yong, Manja Lehmann, Nilufer Ertekin-Taner, Neill R. Graff-Radford, Bradley F. Boeve, Melissa E. Murray, Qurat ul Ain Khan, Ronald C. Petersen, Dennis W. Dickson, David S. Knopman, Gil D. Rabinovici, Bruce L. Miller, Aida Suárez González, Eulogio Gil-Néciga, Julie S. Snowden, Jenny Harris, Stuart M. Pickering-Brown, Eva Louwersheimer, Wiesje M. van der Flier, Philip Scheltens, Yolande A. Pijnenburg, Douglas Galasko, Marie Sarazin, Bruno Dubois, Eloi Magnin, Daniela Galimberti, Elio Scarpini, Stefano F. Cappa, John R. Hodges, Glenda M. Halliday, Lauren Bartley, Maria C. Carrillo, Jose T. Bras, John Hardy, Martin N. Rossor, John Collinge, Nick C. Fox, Simon Mead
      Introduction The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. Methods We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study. Results We confirm that variation in/near APOE/TOMM40 (P = 6 × 10−14) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, P = .0007). We found evidence for risk in/near CR1 (P = 7 × 10−4), ABCA7 (P = .02) and BIN1 (P = .04). ORs at variants near INPP5D and NME8 did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed APOE and identified three novel loci: rs76854344 near CNTNAP5 (P = 8 × 10−10 OR = 1.9 [1.5–2.3]); rs72907046 near FAM46A (P = 1 × 10−9 OR = 3.2 [2.1–4.9]); and rs2525776 near SEMA3C (P = 1 × 10−8, OR = 3.3 [2.1–5.1]). Discussion We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD.

      PubDate: 2018-01-04T22:23:38Z
  • Exploring APOE genotype effects on AD risk and β-amyloid burden in
           individuals with subjective cognitive decline: The FACEHBI study baseline
    • 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
    • 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 ( 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
    • 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
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