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Publisher: Elsevier   (Total: 3163 journals)

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Showing 1 - 200 of 3163 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 30, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 88, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 35, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 394, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 244, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 16, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3, SJR: 0.732, CiteScore: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 134, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 29, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 23)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 43, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 37, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 16, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
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: 19, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 385, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 10, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 335, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 10, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 436, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 10, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 50, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 51, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 43)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 203, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 63, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 15, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 174, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)

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Journal Cover
Alzheimer's & Dementia: Translational Research & Clinical Interventions
Journal Prestige (SJR): 1.108
Citation Impact (citeScore): 3
Number of Followers: 4  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2352-8737
Published by Elsevier Homepage  [3163 journals]
  • Efficacy and safety of the compound Chinese medicine SaiLuoTong
           in vascular dementia: A randomized clinical trial

    • Authors: Jianping Jia; Cuibai Wei; Shuoqi Chen; Fangyu Li; Yi Tang; Wei Qin; Lu Shi; Min Gong; Hui Xu; Fang Li; Jia He; Haiqing Song; Shanshan Yang; Aihong Zhou; Fen Wang; Xiumei Zuo; Changbiao Chu; Junhua Liang; Longfei Jia; Serge Gauthier
      Pages: 108 - 117
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4
      Author(s): Jianping Jia, Cuibai Wei, Shuoqi Chen, Fangyu Li, Yi Tang, Wei Qin, Lu Shi, Min Gong, Hui Xu, Fang Li, Jia He, Haiqing Song, Shanshan Yang, Aihong Zhou, Fen Wang, Xiumei Zuo, Changbiao Chu, Junhua Liang, Longfei Jia, Serge Gauthier
      Introduction No licensed medications are available to treat vascular dementia (VaD). Methods Patients were randomly assigned to experimental groups (SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52, respectively). Results Three hundred twenty-five patients were included in final analysis. At week 26, the difference in VaD Assessment Scale–cognitive subscale scores was 2.67 (95% confidence interval, 1.54 to 3.81) for groups A versus C, and 2.48 (1.34 to 3.62) for groups B versus C (both P < .0001). However, at week 52, no difference was observed among the groups on the VaD Assessment Scale–cognitive subscale (P = .062) because of the emerging efficacy of SLT in placebo beginning at week 27. Discussion This study suggests that SLT is effective for treatment of VaD, and this compound Chinese medicine may represent a better choice to treat VaD.

      PubDate: 2018-04-15T15:00:55Z
      DOI: 10.1016/j.trci.2018.02.004
      Issue No: Vol. 4 (2018)
       
  • Virtual reality-based cognitive-motor training for middle-aged adults at
           high Alzheimer's disease risk: A randomized controlled trial

    • Authors: Glen M. Doniger; Michal Schnaider Beeri; Alex Bahar-Fuchs; Amihai Gottlieb; Anastasia Tkachov; Hagar Kenan; Abigail Livny; Yotam Bahat; Hadar Sharon; Oran Ben-Gal; Maya Cohen; Gabi Zeilig; Meir Plotnik
      Pages: 118 - 129
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4
      Author(s): Glen M. Doniger, Michal Schnaider Beeri, Alex Bahar-Fuchs, Amihai Gottlieb, Anastasia Tkachov, Hagar Kenan, Abigail Livny, Yotam Bahat, Hadar Sharon, Oran Ben-Gal, Maya Cohen, Gabi Zeilig, Meir Plotnik
      Introduction Ubiquity of Alzheimer's disease (AD) coupled with relatively ineffectual pharmacologic treatments has spurred interest in nonpharmacologic lifestyle interventions for prevention or risk reduction. However, evidence of neuroplasticity notwithstanding, there are few scientifically rigorous, ecologically relevant brain training studies focused on building cognitive reserve in middle age to protect against cognitive decline. This pilot study will examine the ability of virtual reality (VR) cognitive training to improve cognition and cerebral blood flow (CBF) in middle-aged individuals at high AD risk due to parental history. Methods The design is an assessor-blind, parallel group, randomized controlled trial of VR cognitive-motor training in middle-aged adults with AD family history. The experimental group will be trained with adaptive “real-world” VR tasks targeting sustained and selective attention, working memory, covert rule deduction, and planning, while walking on a treadmill. One active control group will perform the VR tasks without treadmill walking; another will walk on a treadmill while watching scientific documentaries (nonspecific cognitive stimulation). A passive (waitlist) control group will not receive training. Training sessions will be 45 minutes, twice/week for 12 weeks. Primary outcomes are global cognition and CBF (from arterial spin labeling [ASL]) at baseline, immediately after training (training gain), and 3 months post-training (maintenance gain). We aim to recruit 125 participants, including 20 passive controls and 35 in the other groups. Discussion Current pharmacologic therapies are for symptomatic AD patients, whereas nonpharmacologic training is administrable before symptom onset. Emerging evidence suggests that cognitive training improves cognitive function. However, a more ecologically valid cognitive-motor VR setting that better mimics complex daily activities may augment transfer of trained skills. VR training has benefited clinical cohorts, but benefit in asymptomatic high-risk individuals is unknown. If effective, this trial may help define a prophylactic regimen for AD, adaptable for home-based application in high-risk individuals.

      PubDate: 2018-04-15T15:00:55Z
      DOI: 10.1016/j.trci.2018.02.005
      Issue No: Vol. 4 (2018)
       
  • Discontinuation and nonpublication of interventional clinical trials
           conducted in patients with mild cognitive impairment and Alzheimer's
           disease

    • Authors: Taygan Yilmaz; Roos J. Jutten; Cláudia Y. Santos; Kimberly A. Hernandez; Peter J. Snyder
      Pages: 161 - 164
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4
      Author(s): Taygan Yilmaz, Roos J. Jutten, Cláudia Y. Santos, Kimberly A. Hernandez, Peter J. Snyder
      Introduction Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimer's disease. Methods We conducted a retrospective, cross-sectional study on mild cognitive impairment and Alzheimer's disease–based interventional clinical trials in ClinicalTrials.gov dating back to 1995. The analyzed data included trial phase, intervention type, enrollment, and funding sources. Fisher's exact and χ2 tests were used to determine any potential associations between trial characteristics and completion. Results A total of 744 studies were identified, of which 502 (67%) were industry-sponsored ones. A total of 127 (17%) were discontinued prematurely. Of the 617 completed trials, 450 (73%) were not published, representing approximately 66,655 participants who incurred the risks of trial participation without subsequently contributing to the medical literature. Similarly, there were 18,246 patients from unpublished, discontinued trials. Of the 744 trials examined, 247 publications from 167 trials could be identified via PubMed/MEDLINE and EMBASE searches. Most notably, the odds of nonpublication among industry-sponsored trials were more than 75% higher than those in studies funded by academia (odds ratio = 1.78; 95% confidence interval, 1.14–2.78; P = .01). Furthermore, industry-sponsored trials had a 50% greater odds of study discontinuation compared with trials funded by academia (odds ratio = 1.50; 95% confidence interval, 1.04–2.16; P = .03). Discussion The nonpublication of many trials and preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Publication of inconclusive or negative results ensures that all research activities, regardless of outcome, contribute to global medical knowledge.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.03.005
      Issue No: Vol. 4 (2018)
       
  • Galectin-3 and incident cognitive impairment in REGARDS, a cohort of
           blacks and whites

    • Authors: Anand Venkatraman; Peter Callas; Leslie A. McClure; Fred Unverzagt; Garima Arora; Virginia Howard; Virginia G. Wadley; Mary Cushman; Pankaj Arora
      Pages: 165 - 172
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4
      Author(s): Anand Venkatraman, Peter Callas, Leslie A. McClure, Fred Unverzagt, Garima Arora, Virginia Howard, Virginia G. Wadley, Mary Cushman, Pankaj Arora
      Introduction The relationship between serum galectin-3 and incident cognitive impairment was analyzed in the Reasons for Geographic and Racial Differences in Stroke study. Methods Baseline galectin-3 was measured in 455 cases of incident cognitive impairment and 546 controls. Galectin-3 was divided into quartiles based on the weighted distribution in the control group, and the first quartile was the referent. Results There was an increasing odds of cognitive impairment across quartiles of galectin-3 (odds ratios, 1.00 [0.68–1.46], 1.45 [1.01–2.10], and 1.58 [1.10–2.27] relative to the quartile 1; P trend = .003) in an unadjusted model, which persisted after adjusting for age, sex, and race (P = .004). Adjustment for cardiovascular risk factors greatly attenuated this association (odds ratios, 0.97 [0.60–1.57], 1.52 [0.94–2.46], and 1.27 [0.76–2.12]; P = .15). The association differed by diabetes status (P interaction, .007). Among nondiabetics (293 cases, 411 controls), those with galectin-3 in the fourth compared with first quartile had an odds ratio of 1.6 (0.95–2.99; P trend, .02). In diabetics, the odds ratio was 0.23 (0.04–1.33). Discussion Serum galectin-3 was associated with increased risk of incident cognitive impairment in a large cohort study of blacks and whites but only in nondiabetics.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.03.006
      Issue No: Vol. 4 (2018)
       
  • Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's
           disease

    • Authors: Tiffini Voss; Jerry Li; Jeffrey Cummings; Martin Farlow; Christopher Assaid; Samar Froman; Heather Leibensperger; Linda Snow-Adami; Kerry Budd McMahon; Michael Egan; David Michelson
      Pages: 173 - 181
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4
      Author(s): Tiffini Voss, Jerry Li, Jeffrey Cummings, Martin Farlow, Christopher Assaid, Samar Froman, Heather Leibensperger, Linda Snow-Adami, Kerry Budd McMahon, Michael Egan, David Michelson
      Introduction We evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease. Methods A randomized, double-blind, proof-of-concept trial was performed. Participants with mild-to-moderate Alzheimer's disease, being treated with an acetylcholinesterase inhibitor, were randomized 1:1 to 45 mg of MK-7622 or placebo for 24 weeks. Endpoints included the mean change from baseline in Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) at 12 weeks and Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory at 24 weeks. Results Two hundred forty participants were randomized. The trial was stopped for futility after meeting prospectively defined stopping criteria. MK-7622 did not improve cognition at 12 weeks (group difference in ADAS-Cog11: 0.18 [95% confidence interval: −1.0 to 1.3]) or function at 24 weeks (group difference in Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory: 0.06 [95% confidence interval: −2.4 to 2.5]). More participants taking MK-7622 discontinued study medication because of adverse events than those taking placebo (16% vs 6%) and who experienced cholinergically related adverse events (21% vs 8%). Discussion MK-7622 (45 mg) does not improve cognition or function when used as adjunctive therapy in mild-to-moderate Alzheimer's disease.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.03.004
      Issue No: Vol. 4 (2018)
       
  • Lifestyle and neurodegeneration in midlife as expressed on functional
           magnetic resonance imaging: A systematic review

    • Authors: Hinesh Topiwala; Graciela Muniz Terrera; Lucy Stirland; Kathryn Saunderson; Tom C. Russ; Marshall F. Dozier; Craig W. Ritchie
      Pages: 182 - 194
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4
      Author(s): Hinesh Topiwala, Graciela Muniz Terrera, Lucy Stirland, Kathryn Saunderson, Tom C. Russ, Marshall F. Dozier, Craig W. Ritchie
      Introduction Lifestyle factors may influence brain health in midlife. Functional magnetic resonance imaging is a widely used tool to investigate early changes in brain health, including neurodegeneration. In this systematic review, we evaluate the relationship between lifestyle factors and neurodegeneration in midlife, as expressed using functional magnetic resonance imaging. Methods We searched MEDLINE, EMBASE, and PsycINFO combining subject headings and free text terms adapted for each database. Articles were screened, and their quality was assessed independently by two reviewers before final inclusion in the review. Results We screened 4116 studies and included 29 in the review. Seven lifestyle factors, such as alcohol, cognitive training, excessive internet use, fasting, physical training, smoking, and substance misuse, were identified in this review. Discussion Cognitive and physical trainings appear to be associated with a neuroprotective effect, whereas alcohol misuse, smoking, and substance misuse appear to be associated with neurodegeneration. Further research is required into the effects of excessive internet use and fasting.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.04.001
      Issue No: Vol. 4 (2018)
       
  • From information to follow-up: Ethical recommendations to facilitate the
           disclosure of amyloid PET scan results in a research setting

    • Authors: Gwendolien Vanderschaeghe; Jolien Schaeverbeke; Rose Bruffaerts; Rik Vandenberghe; Kris Dierickx
      Abstract: Publication date: Available online 24 May 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Gwendolien Vanderschaeghe, Jolien Schaeverbeke, Rose Bruffaerts, Rik Vandenberghe, Kris Dierickx
      In the field of Alzheimer's disease research, the use of biomarkers such as amyloid positron emission tomography (PET) has become widespread over a relatively brief period of time. There is an increasing tendency in research studies and trials to switch from no disclosure under any condition toward a qualified disclosure of individual research results, such as amyloid PET scan results. This perspective article aims to evaluate the possible need for a modification of the available recommendations on amyloid PET scan disclosure, based on recent empirical evidence obtained within the field of amyloid PET. This article also applies the International Guideline for Good Clinical Practice to the field of amyloid PET disclosure. Hence, we propose several recommendations (abbreviated as the IDT CRP method) to facilitate amyloid PET disclosure while minimizing possible risks of amyloid disclosure in a research context.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.04.002
       
  • Nuclear factor-kappa B: Glucocorticoid-induced leucine zipper interface
           analogs suppress pathology in an Alzheimer's disease model

    • Authors: Mythily Srinivasan; Niloy Lahiri; Anish Thyagarajan; Emily Witek; Debra Hickman; Debomoy K. Lahiri
      Abstract: Publication date: Available online 24 May 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Mythily Srinivasan, Niloy Lahiri, Anish Thyagarajan, Emily Witek, Debra Hickman, Debomoy K. Lahiri
      Background Glucocorticoid-induced leucine zipper is a regulatory protein that sequesters activated nuclear factor-kappa B p65. Previously, we showed that rationally designed analogs of the p65-binding domain of glucocorticoid-induced leucine zipper, referred to as glucocorticoid-induced leucine zipper analogs (GAs), inhibited amyloid β–induced metabolic activity and inflammatory cytokines in mixed brain cell cultures. Here, we investigate the therapeutic efficacy of GA in an Alzheimer's disease model. Methods GA and control peptides were synthesized covalently as peptide amides with the cell-penetrating agent. C57Bl/6J mice induced with lipopolysaccharide-mediated neuroinflammation (250 mg/kg i.p/day for six days) were treated on alternate days with GA-1, GA-2, or control peptides (25 mg/kg i.v). Brain tissues were assessed for gliosis, cytokines, and antiapoptotic factors. Results The brain tissues of GA-1– and GA-2–treated mice exhibited significantly reduced gliosis, suppressed inflammatory cytokines, and elevated antiapoptotic factors. Discussion The antineuroinflammatory effects of GA suggest potential therapeutic application for Alzheimer's disease.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.04.004
       
  • Established amyloid-β pathology is unaffected by chronic treatment with
           the selective serotonin reuptake inhibitor paroxetine

    • Authors: Maurizio Severino; Mithula Sivasaravanaparan; Louise Ø. Olesen; Christian U. von Linstow; Athanasios Metaxas; Elena V. Bouzinova; Asif Manzoor Khan; Kate L. Lambertsen; Alicia A. Babcock; Jan Bert Gramsbergen; Ove Wiborg; Bente Finsen
      Abstract: Publication date: Available online 24 May 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Maurizio Severino, Mithula Sivasaravanaparan, Louise Ø. Olesen, Christian U. von Linstow, Athanasios Metaxas, Elena V. Bouzinova, Asif Manzoor Khan, Kate L. Lambertsen, Alicia A. Babcock, Jan Bert Gramsbergen, Ove Wiborg, Bente Finsen
      Introduction Treatment with selective serotonin reuptake inhibitors has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to an antidepressant mechanism of action. Methods We investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic APPswe/PS1ΔE9 mutants. In addition, we addressed whether serotonin depletion affects Aβ pathology. Treatments were assessed by measurement of serotonin transporter occupancy and high-performance liquid chromatography. The effect of paroxetine on Aβ pathology was evaluated by stereological plaque load estimation and Aβ42/Aβ40 ratio by ELISA. Results Contrary to our hypothesis, paroxetine therapy did not mitigate Aβ pathology, and depletion of brain serotonin did not exacerbate Aβ pathology. However, chronic paroxetine therapy increased mortality in APPswe/PS1ΔE9 transgenic mice. Discussion Our results question the ability of selective serotonin reuptake inhibitor therapy to ameliorate established Aβ pathology. The severe adverse effect of paroxetine may discourage its use for disease-modifying purposes in Alzheimer's disease.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.04.005
       
  • Neural correlates of episodic memory in the Memento cohort

    • Authors: Stephane Epelbaum; Vincent Bouteloup; Jean F. Mangin; Valentina La Corte; Raffaela Migliaccio; Hugo Bertin; Marie O. Habert; Clara Fischer; Chabha Azouani; Ludovic Fillon; Marie Chupin; Bruno Vellas; Florence Pasquier; Jean F. Dartigues; Fréderic Blanc; Audrey Gabelle; Mathieu Ceccaldi; Pierre Krolak-Salmon; Jacques Hugon; Olivier Hanon; Olivier Rouaud; Renaud David; Genevieve Chêne; Bruno Dubois; Carole Dufouil
      Abstract: Publication date: Available online 22 May 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Stephane Epelbaum, Vincent Bouteloup, Jean F. Mangin, Valentina La Corte, Raffaela Migliaccio, Hugo Bertin, Marie O. Habert, Clara Fischer, Chabha Azouani, Ludovic Fillon, Marie Chupin, Bruno Vellas, Florence Pasquier, Jean F. Dartigues, Fréderic Blanc, Audrey Gabelle, Mathieu Ceccaldi, Pierre Krolak-Salmon, Jacques Hugon, Olivier Hanon, Olivier Rouaud, Renaud David, Genevieve Chêne, Bruno Dubois, Carole Dufouil
      Introduction The free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory. Methods We investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose–positron emission tomography evaluations. Results Encoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions. Discussion The neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied.

      PubDate: 2018-05-31T23:01:26Z
      DOI: 10.1016/j.trci.2018.03.010
       
  • Wishes and preferences for an online lifestyle program for brain
           health—A mixed methods study

    • Authors: Linda Maria Petronella Wesselman; Ann-Katrin Schild; Nina Coll-Padros; Wieke E. van der Borg; Judith H.P. Meurs; Astrid M. Hooghiemstra; Rosalinde E.R. Slot; Lena Sannemann; Lorena Rami; José Luis Molinuevo; Femke H. Bouwman; Frank Jessen; Wiesje M. van der Flier; Sietske A.M. Sikkes
      Abstract: Publication date: Available online 9 April 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Linda Maria Petronella Wesselman, Ann-Katrin Schild, Nina Coll-Padros, Wieke E. van der Borg, Judith H.P. Meurs, Astrid M. Hooghiemstra, Rosalinde E.R. Slot, Lena Sannemann, Lorena Rami, José Luis Molinuevo, Femke H. Bouwman, Frank Jessen, Wiesje M. van der Flier, Sietske A.M. Sikkes
      Introduction Individuals with subjective cognitive decline (SCD) are at increased risk of Alzheimer's disease and could benefit from a prevention strategy targeting lifestyle factors. Making a program available through the Internet gives a widespread reach at low cost, but suboptimal adherence is a major threat to effectiveness. As a first step in developing an online lifestyle program (OLP), we aimed to identify factors that are barriers and/or facilitators for the use of an OLP in individuals with SCD in three European countries. Methods As part of the Euro-SCD project, SCD subjects were recruited at memory clinics in the Netherlands, Germany, and Spain. We combined quantitative and qualitative methods, using a mixed methods approach. We conducted an online 18-item survey on the preferences of SCD patients for an OLP (N = 238). In addition, we held semi-structured interviews (N = 22) to gain in-depth understanding of factors acting as a facilitator and/or barrier for intended use of an OLP. Audio recordings were transcribed verbatim. Content analysis was performed. Results One hundred seventy-six individuals completed the survey (response rate 74%). Almost all participants regularly use the Internet (97%). Participants reported trustworthiness (93%), user-friendliness (91%), and up-to-date information (88%) as main facilitators, whereas having contact with other users (26%), needing an account (21%), and assignments (16%) were reported as barriers. Barriers differed slightly between countries, but facilitators were largely similar. In-depth interviews revealed that both program characteristics (e.g., trustworthiness, user-friendliness, and personalization) and personal factors (e.g., expectancy to receive negative feedback) are likely to influence the intended use of an OLP. Discussion Involving users provided in-depth understanding of factors associated with the intended use of an OLP for brain health. Both program characteristics and personal factors are likely to influence the use of an OLP. Based on this input from the end-users, we will develop an OLP for individuals with SCD.

      PubDate: 2018-04-15T15:00:55Z
      DOI: 10.1016/j.trci.2018.03.003
       
  • “Text It” program to track falls in patients with Alzheimer's
           disease and dementia

    • Authors: Rebecca J. Kamil; Dara Bakar; Matthew Ehrenburg; Scott Frankenthaler; Eric X. Wei; Eric Anson; Esther Oh; Yuri Agrawal
      Abstract: Publication date: Available online 7 April 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Rebecca J. Kamil, Dara Bakar, Matthew Ehrenburg, Scott Frankenthaler, Eric X. Wei, Eric Anson, Esther Oh, Yuri Agrawal
      Introduction Falls are a significant problem among older adults with Alzheimer's disease, leading to high rates of fracture, hospitalization, and death. Tracking falls in older adults, particularly those with cognitive impairment, is a clinical and research challenge. Methods This prospective pilot study evaluated the feasibility of a text message program to track falls among patients with dementia. We also compared this technique with the calendar method of fall data collection. Results There was a 96% completion rate of text messaging and 100% of calendars; however, the text-gathered data were more accurate. Discussion A text-messaging platform to track falls shows promise in cognitively impaired individuals.

      PubDate: 2018-04-15T15:00:55Z
      DOI: 10.1016/j.trci.2018.03.001
       
  • Effect of donepezil on transcranial magnetic stimulation parameters in
           Alzheimer's disease

    • Authors: Yun Tae Hwang; Lorenzo Rocchi; Paul Hammond; Chris JD. Hardy; Jason D. Warren; Basil H. Ridha; John Rothwell; Martin N. Rossor
      Abstract: Publication date: Available online 2 March 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Yun Tae Hwang, Lorenzo Rocchi, Paul Hammond, Chris JD. Hardy, Jason D. Warren, Basil H. Ridha, John Rothwell, Martin N. Rossor
      Introduction There is a need for a reliable, noninvasive biomarker for Alzheimer's disease (AD). We assessed whether short-latency afferent inhibition (SAI), a transcranial magnetic stimulation paradigm that assesses cholinergic circuits of the brain, could become such a biomarker. Methods Nineteen patients with AD underwent four SAI testing sessions. The timing of their usual donepezil dose was altered to create different cholinergic states for each session. This was compared to the SAI results from 20 healthy subjects. Results SAI was not able to distinguish the different cholinergic states assessed in our study. There appeared to be a diurnal variation in cholinergic function in the control group, which was not present in the AD cohort. Discussion SAI does not appear to have a role in diagnosis and assessment of AD patients. The loss of diurnal variation, however, warrants further investigation as it may provide further biochemical insights about AD.

      PubDate: 2018-03-07T10:18:52Z
      DOI: 10.1016/j.trci.2018.02.001
       
  • Alzheimer's disease Archimedes condition-event simulator: Development and
           validation

    • Authors: Anuraag R. Kansal; Ali Tafazzoli; K. Jack Ishak; Stanmira Krotneva
      Abstract: Publication date: Available online 16 February 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Anuraag R. Kansal, Ali Tafazzoli, K. Jack Ishak, Stanmira Krotneva
      Introduction Several advances have been made in Alzheimer's Disease (AD) modeling, however, there remains a need for a simulator that represents the full scope of disease progression and can be used to study new disease-modifying treatments for early-stage and even prodromal AD. Methods We developed AD Archimedes condition-event simulator, a patient-level simulator with a focus on simulating the effects of early interventions through changes in biomarkers of AD. The simulator incorporates interconnected predictive equations derived from longitudinal data sets. Results The results of external validations on AD Archimedes condition-event simulator showed that it provides reasonable estimates once compared to literature results on transition to dementia AD, institutionalization, and mortality. A case study comparing a disease-modifying treatments and a symptomatic treatment also showcases the benefits of early treatment. Discussion The AD Archimedes condition-event simulator is designed to perform economic evaluation on various interventions through close tracking of disease progression and the related clinical outcomes.

      PubDate: 2018-02-17T07:15:41Z
      DOI: 10.1016/j.trci.2018.01.001
       
  • Elevated phospholipase D isoform 1 in Alzheimer's disease patients'
           hippocampus: Relevance to synaptic dysfunction and memory deficits

    • Authors: Balaji Krishnan; Rakez Kayed; Giulio Taglialatela
      Abstract: Publication date: Available online 14 February 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Balaji Krishnan, Rakez Kayed, Giulio Taglialatela
      Introduction Phospholipase D (PLD), a lipolytic enzyme that breaks down membrane phospholipids, is also involved in signaling mechanisms downstream of seven transmembrane receptors. Abnormally elevated levels of PLD activity are well-established in Alzheimer's disease (AD), implicating the two isoforms of mammalian phosphatidylcholine cleaving PLD (PC-PLD1 and PC-PLD2). Therefore, we took a systematic approach of investigating isoform-specific expression in human synaptosomes and further investigated the possibility of therapeutic intervention using preclinical studies. Methods Synaptosomal Western blot analyses on the postmortem human hippocampus, temporal cortex, and frontal cortex of AD patient brains/age-matched controls and the 3XTg-AD mice hippocampus (mouse model with overexpression of human amyloid precursor protein, presenilin-1 gene, and microtubule-associated protein tau causing neuropathology progressing comparable to that in human AD patients) were used to detect the levels of neuronal PLD1 expression. Mouse hippocampal long-term potentiation of PLD1-dependent changes was studied using pharmacological approaches in ex vivo slice preparations from wild-type and transgenic mouse models. Finally, PLD1-dependent changes in novel object recognition memory were assessed following PLD1 inhibition. Results We observed elevated synaptosomal PLD1 in the hippocampus/temporal cortex from postmortem tissues of AD patients compared to age-matched controls and age-dependent hippocampal PLD1 increases in 3XTg-AD mice. PLD1 inhibition blocked effects of oligomeric amyloid β or toxic oligomeric tau species on high-frequency stimulation long-term potentiation and novel object recognition deficits in wild-type mice. Finally, PLD1 inhibition blocked long-term potentiation deficits normally observed in aging 3XTg-AD mice. Discussion Using human studies, we propose a novel role for PLD1-dependent signaling as a critical mechanism underlying oligomer-driven synaptic dysfunction and consequent memory disruption in AD. We, further, provide the first set of preclinical studies toward future therapeutics targeting PLD1 in slowing down/stopping the progression of AD-related memory deficits as a complementary approach to immunoscavenging clinical trials that are currently in progress.

      PubDate: 2018-02-17T07:15:41Z
      DOI: 10.1016/j.trci.2018.01.002
       
  • Neuroprotective effect of a new photobiomodulation technique against
           Aβ25–35 peptide–induced toxicity in mice: Novel hypothesis for
           therapeutic approach of Alzheimer's disease suggested

    • Authors: Guillaume Blivet; Johann Meunier; Francois J. Roman; Jacques Touchon
      Abstract: Publication date: Available online 2 February 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Guillaume Blivet, Johann Meunier, Francois J. Roman, Jacques Touchon
      ▪▪▪.

      PubDate: 2018-02-05T20:12:30Z
      DOI: 10.1016/j.trci.2017.12.003
       
  • A simulation study comparing slope model with mixed-model repeated measure
           to assess cognitive data in clinical trials of Alzheimer's disease

    • Authors: Yun-Fei Chen; Xiao Ni; Adam S. Fleisher; Wei Zhou; Paul Aisen; Richard Mohs
      Abstract: Publication date: Available online 18 January 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Yun-Fei Chen, Xiao Ni, Adam S. Fleisher, Wei Zhou, Paul Aisen, Richard Mohs
      Introduction In clinical trials of Alzheimer's disease, a mixed-model repeated measure approach often serves as the primary analysis when evaluating disease progression; a slope model may be secondary. Methods Longitudinal change from baseline (14-item version of Alzheimer's Disease Assessment Scale–Cognitive Subscale) was simulated for treatment/placebo from multivariate normal distributions with the variance-covariance matrix estimated from solanezumab trial data. Type I error, power, and bias were based on 18-month treatment contrast. Sample sizes included 500 and 1000 patients/arm. Results The slope model was more powerful in most scenarios. Mixed-model repeated measure was relatively unbiased in parameter estimation. The slope model yielded unbiased estimates whenever the underlying trajectory was not detectably different from linear. Both methods led to similar type I error. Discussion In clinical trials of Alzheimer's disease, mixed-model repeated measure analysis with relaxed assumptions on disease progression seems to be preferred. The slope model might be more powerful if the trajectory has little departure from linearity.

      PubDate: 2018-01-25T18:53:54Z
      DOI: 10.1016/j.trci.2017.12.002
       
  • Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics,
           and pharmacokinetics in the APP/PS1 mouse

    • Authors: Andrew F. Teich; Ekta Sharma; Eliza Barnwell; Hong Zhang; Agnieszka Staniszewski; Tadanobu Utsuki; Vasudevaraju Padmaraju; Cheryl Mazell; Apostolia Tzekou; Kumar Sambamurti; Ottavio Arancio; Maria L. Maccecchini
      Abstract: Publication date: Available online 18 January 2018
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Andrew F. Teich, Ekta Sharma, Eliza Barnwell, Hong Zhang, Agnieszka Staniszewski, Tadanobu Utsuki, Vasudevaraju Padmaraju, Cheryl Mazell, Apostolia Tzekou, Kumar Sambamurti, Ottavio Arancio, Maria L. Maccecchini
      Introduction Translational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease. Methods We used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics. Results Posiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild-type mice. Posiphen had a prolonged effect in reducing APP and all related peptides for at least 9 hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N8-norPosiphen. Discussion This is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.

      PubDate: 2018-01-25T18:53:54Z
      DOI: 10.1016/j.trci.2017.12.001
       
  • Person-centered care for older people with dementia in the acute hospital

    • Authors: Felicia Hui En Tay; Claire L. Thompson; Chih Ming Nieh; Chih Chiang Nieh; Hui Mien Koh; Jessie Joon Cheen Tan; Philip Lin Kiat Yap
      Abstract: Publication date: Available online 6 December 2017
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Felicia Hui En Tay, Claire L. Thompson, Chih Ming Nieh, Chih Chiang Nieh, Hui Mien Koh, Jessie Joon Cheen Tan, Philip Lin Kiat Yap
      Introduction Patients with dementia (PWDs) are often subjected to enforced dependency and experience functional decline and emotional distress during hospital stay. Person-centered care (PCC) with specialized psychosocial interventions, minimally obtrusive medical care, and physical restraints-free practice holds potential to improve patient outcomes. We evaluate the effectiveness of an acute hospital dementia unit (Care for Acute Mentally Infirm Elders [CAMIE]) that adopts a PCC protocol. Methods Prospective naturalistic cohort study whereby PWDs in the CAMIE unit (n = 170) were compared with a control group in usual care wards (n = 60) over 6 months. Assessments included patient demographics, dementia type and stage, comorbidities (Charlson's Comorbidity Index), acute illness severity, Well-Being, Ill-Being, functional status (Modified Barthel Index), agitation levels (Pittsburgh Agitation Scale), and quality of life (EuroQoL), assessed on admission and discharge. Multivariate analysis of covariance examined the effect of CAMIE versus usual care on pre-post outcomes. Results CAMIE patients showed statistically significant greater gains in Modified Barthel Index function and Well-Being, decreased Ill-Being and agitation, and greater improvement in EuroQoL index score (effect size: Δ = 0.18) after adjusting for baseline differences that translated to a quality-adjusted life years gain of 0.045, assuming stability over 3 months. Estimating added cost of CAMIE stay over usual care at SGD 1500 (USD 1040) for average length of stay of 15 days per patient, the incremental cost-effectiveness ratio fell within the threshold for cost-effectiveness at USD 23,111. Discussion PCC for PWDs in acute hospitals not only improves clinical outcomes for patients but is also cost-effective. The results support the adoption of PCC on a wider scale for better care of PWDs.

      PubDate: 2017-12-10T12:40:25Z
      DOI: 10.1016/j.trci.2017.11.003
       
  • Feasibility and efficacy data from a ketogenic diet intervention in
           Alzheimer's disease

    • Authors: Matthew K. Taylor; Debra K. Sullivan; Jonathan D. Mahnken; Jeffrey M. Burns; Russell H. Swerdlow
      Abstract: Publication date: Available online 6 December 2017
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Matthew K. Taylor, Debra K. Sullivan, Jonathan D. Mahnken, Jeffrey M. Burns, Russell H. Swerdlow
      Introduction We assessed the feasibility and cognitive effects of a ketogenic diet (KD) in participants with Alzheimer's disease. Methods The Ketogenic Diet Retention and Feasibility Trial featured a 3-month, medium-chain triglyceride–supplemented KD followed by a 1-month washout in clinical dementia rating (CDR) 0.5, 1, and 2 participants. We obtained urine acetoacetate, serum β-hydroxybutyrate, food record, and safety data. We administered the Alzheimer's Disease Assessment Scale-cognitive subscale and Mini–Mental State Examination before the KD, and following the intervention and washout. Results We enrolled seven CDR 0.5, four CDR 1, and four CDR 2 participants. One CDR 0.5 and all CDR 2 participants withdrew citing caregiver burden. The 10 completers achieved ketosis. Most adverse events were of medium-chain triglyceride–related. Among the completers, the mean of the Alzheimer's Disease Assessment Scale-cognitive subscale score improved by 4.1 points during the diet (P = .02) and reverted to baseline after the washout. Conclusion This pilot trial justifies KD studies in mild Alzheimer's disease.

      PubDate: 2017-12-10T12:40:25Z
      DOI: 10.1016/j.trci.2017.11.002
       
  • Unmasking the benefits of donepezil via psychometrically precise
           identification of mild cognitive impairment: A secondary analysis of the
           ADCS vitamin E and donepezil in MCI study

    • Authors: Emily C. Edmonds; M. Colin Ard; Steven D. Edland; Douglas R. Galasko; David P. Salmon; Mark W. Bondi
      Abstract: Publication date: Available online 1 December 2017
      Source:Alzheimer's & Dementia: Translational Research & Clinical Interventions
      Author(s): Emily C. Edmonds, M. Colin Ard, Steven D. Edland, Douglas R. Galasko, David P. Salmon, Mark W. Bondi
      Introduction Criteria for mild cognitive impairment (MCI) used in many clinical trials are susceptible to “false-positive (FP)” errors that can be avoided by an “actuarial” psychometric approach. Methods Cluster analysis was applied to baseline neuropsychological test data from 756 MCI participants in the Alzheimer's Disease Cooperative Study donepezil trial. Treatment groups were compared after “FP” MCI cases were removed. Results Cluster analyses revealed three groups: “single-domain amnestic MCI” (31%), “multidomain amnestic MCI” (39%), and “FP MCI” (30%). After removing FP MCI cases, the donepezil treatment group had a lower rate of progression to Alzheimer's disease and better performance on cognitive tests than the placebo/vitamin E group. Discussion Removal of “FP” MCI diagnoses unmasked beneficial effects of donepezil, despite a 30% reduction in sample size. MCI subject selection based on actuarial methods with comprehensive neuropsychological test data can result in more efficient clinical trials and improved ability to detect treatment effects.

      PubDate: 2017-12-10T12:40:25Z
      DOI: 10.1016/j.trci.2017.11.001
       
 
 
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