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Publisher: Elsevier   (Total: 3168 journals)

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Showing 1 - 200 of 3168 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 39, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 26, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 105, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 42, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 7)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6)
Acta Astronautica     Hybrid Journal   (Followers: 453, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 30, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 5, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 330, 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: 12, 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: 2, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 26, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 7, 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: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
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: 18, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 13, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 196, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 12, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 17, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 30, 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: 12, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 12, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, 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: 1, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 35, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, 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: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 29, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 11, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 11, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 20, 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: 16)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 13)
Advances in Digestive Medicine     Open Access   (Followers: 12)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 29, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 52, 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: 67, 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: 21, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 7, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, 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: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 3, 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: 10, 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: 9, 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: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 15, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 9, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 25)
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: 5)
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: 18, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, 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: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 19)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 9, 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: 11)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 6)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 68)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 3, 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: 6)
Advances in Space Research     Full-text available via subscription   (Followers: 435, 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: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 37, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 55, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 395, 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: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 489, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 45, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 8, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 12)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, 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: 11, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 54, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 58, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 67, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 47, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 13)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 37, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 29, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 37, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 50)
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: 277, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 66, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, 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: 32, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, 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: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 67, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 25, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
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: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 221, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 25, 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)
Animal Behaviour     Hybrid Journal   (Followers: 233, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 7, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)

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Similar Journals
Journal Cover
Alzheimer's & Dementia: Translational Research & Clinical Interventions
Journal Prestige (SJR): 1.108
Citation Impact (citeScore): 3
Number of Followers: 6  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2352-8737
Published by Elsevier Homepage  [3168 journals]
  • Statistical advances in clinical trials and clinical research

    • Abstract: Publication date: Available online 14 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Guogen Shan, Sarah Banks, Justin B. Miller, Aaron Ritter, Charles Bernick, Joseph Lombardo, Jeffrey L. CummingsAbstractIntroductionNew treatments for neurodegenerative disease are urgently needed, and clinical trial methods are an essential component of new drug development. Although the parallel-group study design for neurological disorder clinical trials is commonly used to test the efficacy of a new treatment as compared to placebo, it does not efficiently use information from the on-going study to increase the success rate of a trial or to stop a trial earlier when the new treatment is indeed ineffective.MethodsWe review some recent advances in designs for clinical trials, including futility designs and adaptive designs.ResultsFutility designs and noninferiority designs are used to test the nonsuperiority and the noninferiority of a new treatment, respectively. We provide some guidance on using these two designs and analyzing data from these studies properly. Adaptive designs are increasingly used in clinical trials to improve the flexibility and efficiency of trials with the potential to reduce resources, time, and costs. We review some typical adaptive designs and new statistical methods to handle the statistical challenges from adaptive designs.DiscussionStatistical advances in clinical trial designs may be helpful to shorten trial times and benefit more patients being treated with a better treatment during the discovery of new therapies for neurological disorders. Advancing statistical underpinnings of neuroscience research is a critical aspect of the core activities supported by the Center of Biomedical Research Excellence award supporting the Center for Neurodegeneration and Translational Neuroscience.
       
  • Advances in functional magnetic resonance imaging data analysis methods
           using Empirical Mode Decomposition to investigate temporal changes in
           early Parkinson's disease

    • Abstract: Publication date: Available online 14 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Dietmar Cordes, Xiaowei Zhuang, Muhammad Kaleem, Karthik Sreenivasan, Zhengshi Yang, Virendra Mishra, Sarah Banks, Brent Bluett, Jeffrey L. CummingsAbstractIntroductionPrevious neuroimaging studies of Parkinson's disease (PD) patients have shown changes in whole-brain functional connectivity networks. Whether connectivity changes can be detected in the early stages (first 3 years) of PD by resting-state functional magnetic resonance imaging (fMRI) remains elusive. Research infrastructure including MRI and analytic capabilities is required to investigate this issue. The NIH/NIGMS Center for Biomedical Research Excellence awards support infrastructure to advance research goals.MethodsStatic and dynamic functional connectivity analyses were conducted on early stage never-medicated PD subjects (N = 18) and matched healthy controls (N = 18) from the Parkinson's Progression Markers Initiative.ResultsAltered static and altered dynamic functional connectivity patterns were found in early PD resting-state fMRI data. Most static networks (with the exception of the default mode network) had a reduction in frequency and energy in specific low-frequency bands. Changes in dynamic networks in PD were associated with a decreased switching rate of brain states.DiscussionThis study demonstrates that in early PD, resting-state fMRI networks show spatial and temporal differences of fMRI signal characteristics. However, the default mode network was not associated with any measurable changes. Furthermore, by incorporating an optimum window size in a dynamic functional connectivity analysis, we found altered whole-brain temporal features in early PD, showing that PD subjects spend significantly more time than healthy controls in a specific brain state. These findings may help in improving diagnosis of early never-medicated PD patients. These key observations emerged in a Center for Biomedical Research Excellence–supported research environment.
       
  • Current understanding of magnetic resonance imaging biomarkers and memory
           in Alzheimer's disease

    • Abstract: Publication date: Available online 14 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Ece Bayram, Jessica Z.K. Caldwell, Sarah J. BanksAbstractAlzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research. The most established magnetic resonance imaging (MRI) finding is hippocampal atrophy, which is related to memory decline and currently used as a diagnostic criterion for AD. While the medial temporal lobes are impacted early by the spread of neurofibrillary tangles, other networks and regional changes can be found quite early in the progression. Atrophy in several frontal and parietal regions, cortical thinning, and white matter alterations correlate with memory deficits in early AD. Changes in activation and connectivity have been detected by functional MRI (fMRI). Task-based fMRI studies have revealed medial temporal lobe hypoactivation, parietal hyperactivation, and frontal hyperactivation in AD during memory tasks, and activation patterns of these regions are also altered in preclinical and prodromal AD. Resting state fMRI has revealed alterations in default mode network activity related to memory in early AD. These studies are limited in part due to the historic inclusion of patients who had suspected AD but likely did not have the disorder. Modern biomarkers allow for more diagnostic certainty, allowing better understanding of neuroimaging markers in true AD, even in the preclinical stage. Larger patient cohorts, comparison of candidate imaging biomarkers to more established biomarkers, and inclusion of more detailed neuropsychological batteries to assess multiple aspects of memory are needed to better understand the memory deficit in AD and help develop new biomarkers. This article reviews MRI findings related to episodic memory impairments in AD and introduces a new study with multimodal imaging and comprehensive neuropsychiatric evaluation to overcome current limitations.
       
  • The price of progress: Funding and financing Alzheimer's disease drug
           development

    • Abstract: Publication date: Available online 13 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Jeffrey Cummings, Carl Reiber, Parvesh KumarAbstractIntroductionAdvancing research and treatment for Alzheimer's disease (AD) and the search for effective treatments depend on a complex financial ecosystem involving federal, state, industry, advocacy, venture capital, and philanthropy funding approaches.MethodsWe conducted an expert review of the literature pertaining to funding and financing of translational research and drug development for AD.ResultsThe federal government is the largest public funder of research in AD. The NIA, National Institute of Mental Health, National Institute of General Medical Sciences, and National Center for Advancing Translational Science all fund aspects of research in AD drug development. Non-National Institutes of Health federal funding comes from the National Science Foundation, Veterans Administration, Food and Drug Administration, and the Center for Medicare and Medicaid Services. Academic Medical Centers host much of the federally funded basic science research and are increasingly involved in drug development. Funding of the “Valley of Death” involves philanthropy and federal funding through small business programs and private equity from seed capital, angel investors, and venture capital companies. Advocacy groups fund both basic science and clinical trials. The Alzheimer Association is the advocacy organization with the largest research support portfolio relevant to AD drug development. Pharmaceutical companies are the largest supporters of biomedical research worldwide; companies are most interested in late stage de-risked drugs. Drugs progressing into phase II and III are candidates for pharmaceutical industry support through licensing, mergers and acquisitions, and co-development collaborations.DiscussionTogether, the funding and financing entities involved in supporting AD drug development comprise a complex, interactive, dynamic financial ecosystem. Funding source interaction is largely unstructured and available funding is insufficient to meet all demands for new therapies. Novel approaches to funding such as mega-funds have been proposed and more integration of component parts would assist in accelerating drug development.
       
  • Biomedical informatics applications for precision management of
           neurodegenerative diseases

    • Abstract: Publication date: Available online 13 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Justin B. Miller, Guogen Shan, Joseph Lombardo, Gustavo Jimenez-MaggoriaAbstractModern medicine is in the midst of a revolution driven by “big data,” rapidly advancing computing power, and broader integration of technology into healthcare. Highly detailed and individualized profiles of both health and disease states are now possible, including biomarkers, genomic profiles, cognitive and behavioral phenotypes, high-frequency assessments, and medical imaging. Although these data are incredibly complex, they can potentially be used to understand multi-determinant causal relationships, elucidate modifiable factors, and ultimately customize treatments based on individual parameters. Especially for neurodegenerative diseases, where an effective therapeutic agent has yet to be discovered, there remains a critical need for an interdisciplinary perspective on data and information management due to the number of unanswered questions. Biomedical informatics is a multidisciplinary field that falls at the intersection of information technology, computer and data science, engineering, and healthcare that will be instrumental for uncovering novel insights into neurodegenerative disease research, including both causal relationships and therapeutic targets and maximizing the utility of both clinical and research data. The present study aims to provide a brief overview of biomedical informatics and how clinical data applications such as clinical decision support tools can be developed to derive new knowledge from the wealth of available data to advance clinical care and scientific research of neurodegenerative diseases in the era of precision medicine.
       
  • Neuroimaging and neuropsychological assessment of freezing of gait in
           Parkinson's disease

    • Abstract: Publication date: Available online 13 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Brent Bluett, Sarah Banks, Dietmar Cordes, Ece Bayram, Virendra Mishra, Jeffrey Cummings, Irene LitvanAbstractFreezing of gait (FOG) is a disabling phenomenon characterized by a brief, episodic absence or reduction of forward progression of the feet despite the intention to walk. It is a common cause of falls and subsequent morbidity and mortality in Parkinson's disease. There are few therapeutic modalities for FOG; therefore, research to determine the underlying neural mechanisms is paramount. Studies have evaluated the neuropsychological profile of those with FOG in Parkinson's disease or used neuroimaging to identify underlying deficits in structural and functional connectivity. A combined approach longitudinally evaluating the associated cognitive dysfunction and underlying neural networks in FOG is needed. This article reviews neuropsychological and neuroimaging studies to date and introduces a new study of multimodal imaging and cognition in Parkinson's disease FOG. The study demonstrates the use of establishing an infrastructure for studying neurodegenerative disorders using the National Institutes of Health/National Institute of General Medical Science Center of Biomedical Research Excellence grant mechanism.
       
  • Neurodegeneration research: Advances in clinical translational
           neuroscience infrastructure and methods

    • Abstract: Publication date: Available online 1 June 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Jeffrey L. Cummings, Nadia Fulkerson
       
  • Nuclear factor-kappa B: Glucocorticoid-induced leucine zipper interface
           analogs suppress pathology in an Alzheimer's disease model

    • Abstract: Publication date: Available online 24 May 2018Source: Alzheimer's & Dementia: Translational Research & Clinical InterventionsAuthor(s): Mythily Srinivasan, Niloy Lahiri, Anish Thyagarajan, Emily Witek, Debra Hickman, Debomoy K. LahiriAbstractBackgroundGlucocorticoid-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.MethodsGA 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.ResultsThe brain tissues of GA-1– and GA-2–treated mice exhibited significantly reduced gliosis, suppressed inflammatory cytokines, and elevated antiapoptotic factors.DiscussionThe antineuroinflammatory effects of GA suggest potential therapeutic application for Alzheimer's disease.
       
  • Established amyloid-β pathology is unaffected by chronic treatment with
           the selective serotonin reuptake inhibitor paroxetine

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(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 FinsenAbstractIntroductionTreatment 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.MethodsWe investigated whether chronic treatment with paroxetine, a selective serotonin reuptake inhibitor, mitigates Aβ pathology in plaque-bearing double-transgenic amyloid precursor protein (APP)swe/presenilin 1 (PS1)ΔE9 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 enzyme-linked immunosorbent assay.ResultsContrary 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.DiscussionOur 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.
       
  • Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's
           disease

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Tiffini Voss, Jerry Li, Jeffrey Cummings, Martin Farlow, Christopher Assaid, Samar Froman, Heather Leibensperger, Linda Snow-Adami, Kerry Budd McMahon, Michael Egan, David MichelsonAbstractIntroductionWe evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease.MethodsA 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.ResultsTwo 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%).DiscussionMK-7622 (45 mg) does not improve cognition or function when used as adjunctive therapy in mild-to-moderate Alzheimer's disease.
       
  • Galectin-3 and incident cognitive impairment in REGARDS, a cohort of
           blacks and whites

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Anand Venkatraman, Peter Callas, Leslie A. McClure, Fred Unverzagt, Garima Arora, Virginia Howard, Virginia G. Wadley, Mary Cushman, Pankaj AroraAbstractIntroductionThe relationship between serum galectin-3 and incident cognitive impairment was analyzed in the Reasons for Geographic and Racial Differences in Stroke study.MethodsBaseline 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.ResultsThere 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).DiscussionSerum galectin-3 was associated with increased risk of incident cognitive impairment in a large cohort study of blacks and whites but only in nondiabetics.
       
  • Wishes and preferences for an online lifestyle program for brain
           health—A mixed methods study

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Linda M.P. 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, Euro-SCD working groupAbstractIntroductionIndividuals 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.MethodsAs 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.ResultsOne 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.DiscussionInvolving 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.
       
  • Virtual reality-based cognitive-motor training for middle-aged adults at
           high Alzheimer's disease risk: A randomized controlled trial

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(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 PlotnikAbstractIntroductionUbiquity 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.MethodsThe 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.DiscussionCurrent 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.
       
  • Efficacy and safety of the compound Chinese medicine SaiLuoTong
           in vascular dementia: A randomized clinical trial

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(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 GauthierAbstractIntroductionNo licensed medications are available to treat vascular dementia (VaD).MethodsPatients 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).ResultsThree 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 
       
  • Elevated phospholipase D isoform 1 in Alzheimer's disease patients'
           hippocampus: Relevance to synaptic dysfunction and memory deficits

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Balaji Krishnan, Rakez Kayed, Giulio TaglialatelaAbstractIntroductionPhospholipase 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.MethodsSynaptosomal 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.ResultsWe 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.DiscussionUsing 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.
       
  • Alzheimer's disease Archimedes condition-event simulator: Development and
           validation

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Anuraag R. Kansal, Ali Tafazzoli, K. Jack Ishak, Stanmira Krotneva, ADNI CollaborationAbstractIntroductionSeveral 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.MethodsWe 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.ResultsThe 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 treatment and a symptomatic treatment also showcases the benefits of early treatment.DiscussionThe 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.
       
  • 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

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Guillaume Blivet, Johann Meunier, Francois J. Roman, Jacques TouchonAbstractIntroductionPhotobiomodulation was assessed as a novel treatment of Alzheimer’s disease (AD) by the use of a new device RGn500 combining photonic and magnetic emissions in a mouse model of AD.MethodsFollowing the injection of amyloid β 25-35 peptide in male Swiss mice, RGn500 was applied once a day for 7 days either on the top of the head or the center of abdomen or both.ResultsRGn500 daily application for 10 min produced a neuroprotective effect on the neurotoxic effects of amyloid β 25-35 peptide injection when this type of photobiomodulation was applied both on the head and on the abdomen. Protection was demonstrated by memory restoration and on the normalization of key markers of AD (amyloid β 1-42, pTau), oxidative stress (lipid peroxidation), apoptosis (Bax/Bcl2) and neuroinflammation.DiscussionRGn500 displays therapeutic efficacy similar to other pharmacological approaches evaluated in this model of AD.
       
  • A simulation study comparing slope model with mixed-model repeated measure
           to assess cognitive data in clinical trials of Alzheimer's disease

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Yun-Fei Chen, Xiao Ni, Adam S. Fleisher, Wei Zhou, Paul Aisen, Richard MohsAbstractIntroductionIn 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.MethodsLongitudinal 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.ResultsThe 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.DiscussionIn 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.
       
  • Translational inhibition of APP by Posiphen: Efficacy, pharmacodynamics,
           and pharmacokinetics in the APP/PS1 mouse

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(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. MaccecchiniAbstractIntroductionTranslational 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.MethodsWe used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics.ResultsPosiphen 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.DiscussionThis is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.
       
  • Feasibility and efficacy data from a ketogenic diet intervention in
           Alzheimer's disease

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Matthew K. Taylor, Debra K. Sullivan, Jonathan D. Mahnken, Jeffrey M. Burns, Russell H. SwerdlowAbstractIntroductionWe assessed the feasibility and cognitive effects of a ketogenic diet (KD) in participants with Alzheimer's disease.MethodsThe 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.ResultsWe 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 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.DiscussionThis pilot trial justifies KD studies in mild Alzheimer's disease.
       
  • Person-centered care for older people with dementia in the acute hospital

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Felicia Hui En Tay, Claire L. Thompson, Chih Ming Nieh, Chih Chiang Nieh, Hui Mien Koh, Jessie Joon Cheen Tan, Philip Lin Kiat YapAbstractIntroductionPatients 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.MethodsProspective 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.ResultsCAMIE 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.DiscussionPCC 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.
       
  • 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

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Emily C. Edmonds, M. Colin Ard, Steven D. Edland, Douglas R. Galasko, David P. Salmon, Mark W. BondiAbstractIntroductionCriteria 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.MethodsCluster 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.ResultsCluster analyses revealed three groups: “single-domain amnestic MCI” (31%), “multi-domain 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.DiscussionRemoval 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.
       
  • Discontinuation and nonpublication of interventional clinical trials
           conducted in patients with mild cognitive impairment and Alzheimer's
           disease

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Taygan Yilmaz, Roos J. Jutten, Cláudia Y. Santos, Kimberly A. Hernandez, Peter J. SnyderAbstractIntroductionDiscontinuation 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.MethodsWe 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.ResultsA 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).DiscussionThe 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.
       
  • Effect of donepezil on transcranial magnetic stimulation parameters in
           Alzheimer's disease

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Yun Tae Hwang, Lorenzo Rocchi, Paul Hammond, Chris JD. Hardy, Jason D. Warren, Basil H. Ridha, John Rothwell, Martin N. RossorAbstractIntroductionThere 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.MethodsNineteen 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.ResultsSAI 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.DiscussionSAI 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.
       
  • “Text It” program to track falls in patients with Alzheimer's
           disease and dementia

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Rebecca J. Kamil, Dara Bakar, Matthew Ehrenburg, Scott Frankenthaler, Eric X. Wei, Eric Anson, Esther Oh, Yuri AgrawalAbstractIntroductionFalls 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.MethodsThis 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.ResultsThere was a 96% completion rate of text messaging and 100% of calendars; however, the text-gathered data were more accurate.DiscussionA text-messaging platform to track falls shows promise in cognitively impaired individuals.
       
  • From information to follow-up: Ethical recommendations to facilitate the
           disclosure of amyloid PET scan results in a research setting

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Gwendolien Vanderschaeghe, Jolien Schaeverbeke, Rose Bruffaerts, Rik Vandenberghe, Kris DierickxAbstractIn 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 to facilitate amyloid PET disclosure while minimizing possible risks of amyloid disclosure in a research context.
       
  • Lifestyle and neurodegeneration in midlife as expressed on functional
           magnetic resonance imaging: A systematic review

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(s): Hinesh Topiwala, Graciela Muniz Terrera, Lucy Stirland, Kathryn Saunderson, Tom C. Russ, Marshall F. Dozier, Craig W. RitchieAbstractIntroductionLifestyle 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.MethodsWe 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.ResultsWe 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.DiscussionCognitive 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.
       
  • Neural correlates of episodic memory in the Memento cohort

    • Abstract: Publication date: 2018Source: Alzheimer's & Dementia: Translational Research & Clinical Interventions, Volume 4Author(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 HanonAbstractIntroductionThe 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.MethodsWe 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.ResultsEncoding 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.DiscussionThe 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.
       
 
 
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