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Publisher: Elsevier   (Total: 3177 journals)

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Showing 1 - 200 of 3177 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: 28, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 90, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 33, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 378, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 237, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
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Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 131, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
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Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 28, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 0.9, h-index: 30)
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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: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 10)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 6)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 42, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 7)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 15, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 378, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 333, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 9, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 431, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 50, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 43, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 190, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 61, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 164, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)

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Journal Cover Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
  [4 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2352-8729
   Published by Elsevier Homepage  [3177 journals]
  • Advances in Alzheimer's imaging are changing the experience of Alzheimer's
           disease

    • Authors: Shana D. Stites; Richard Milne; Jason Karlawish
      Pages: 285 - 300
      Abstract: Publication date: Available online 19 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Shana D. Stites, Richard Milne, Jason Karlawish
      Neuroimaging is advancing a new definition of Alzheimer's disease (AD). Using imaging biomarkers, clinicians may begin to diagnose the disease by identifying pathology and neurodegeneration in either cognitively impaired or unimpaired adults. This “biomarker-based” diagnosis may allow clinicians novel opportunities to use interventions that either delay the onset or slow the progression of cognitive decline, but it will also bring novel challenges. How will changing the definition of AD from a clinical to a biomarker construct change the experience of living with the disease' Knowledge of AD biomarker status can affect how individuals feel about themselves (internalized stigma) and how others judge them (public stigma). Following a review of AD stigma, we appraise how advances in diagnosis may enable or interrupt its transfer from clinical to preclinical stages and then explore conceptual and pragmatic challenges to addressing stigma in routine care.

      PubDate: 2018-04-15T16:11:10Z
      DOI: 10.1016/j.dadm.2018.02.006
      Issue No: Vol. 10 (2018)
       
  • Retinal oxygen metabolism in patients with mild cognitive impairment

    • Authors: Olof Birna Olafsdottir; Hrafnhildur Sif Saevarsdottir; Sveinn Hakon Hardarson; Kristin Hanna Hannesdottir; Valgerdur Dora Traustadottir; Róbert Arnar Karlsson; Anna Bryndis Einarsdottir; Katrin Dilja Jonsdottir; Einar Stefánsson; Jon Snaedal
      Abstract: Publication date: Available online 1 April 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Olof Birna Olafsdottir, Hrafnhildur Sif Saevarsdottir, Sveinn Hakon Hardarson, Kristin Hanna Hannesdottir, Valgerdur Dora Traustadottir, Róbert Arnar Karlsson, Anna Bryndis Einarsdottir, Katrin Dilja Jonsdottir, Einar Stefánsson, Jon Snaedal
      Introduction We have previously reported that retinal vessel oxygen saturation is increased in mild-to-moderate dementia of Alzheimer's type when compared with healthy individuals. Mild cognitive impairment (MCI) is the predementia stage of the disease. The main purpose was to investigate if these changes are seen in MCI. Methods Retinal vessel oxygen saturation was measured in 42 patients with MCI and 42 healthy individuals with a noninvasive retinal oximeter, Oxymap T1. The groups were paired according to age. Results Arteriolar and venular oxygen saturation was increased in MCI patients compared to healthy individuals (arterioles: 93.1 ± 3.7% vs. 91.1 ± 3.4%, P = .01; venules: 59.6 ± 6.1% vs. 54.9 ± 6.4%, P = .001). Arteriovenous difference was decreased in MCI compared to healthy individuals (33.5 ± 4.5% vs. 36.2 ± 5.2%, P = .01). Discussion Increased retinal vessel oxygen saturation and decreased arteriovenous difference in MCI could reflect less oxygen extraction by retinal tissue. This indicates that retinal oxygen metabolism may be affected in patients with MCI.

      PubDate: 2018-04-15T16:11:10Z
      DOI: 10.1016/j.dadm.2018.03.002
       
  • Memory concerns in the early Alzheimer's disease prodrome: Regional
           association with tau deposition

    • Authors: Cecily G. Swinford; Shannon L. Risacher; Arnaud Charil; Adam J. Schwarz; Andrew J. Saykin
      Abstract: Publication date: Available online 24 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Cecily G. Swinford, Shannon L. Risacher, Arnaud Charil, Adam J. Schwarz, Andrew J. Saykin
      Introduction Relationship between self– and informant memory concerns and tau aggregation was assessed in adults at risk for Alzheimer's disease (AD). Methods Regional mean standardized uptake value ratios were extracted from [18F]flortaucipir positron emission tomography (PET) scans of 82 at-risk adults in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Associations between self– and informant ECog memory scores and tau aggregation were analyzed on both regional and voxelwise bases. Analyses were completed both on the whole sample and restricted to amyloid-positive individuals only. Results Memory concerns were associated with tau aggregation. Self-perception was more associated with frontal tau. In contrast, informant scores were more associated with parietal tau. This source-by-region interaction was more prominent in amyloid-positive participants and observed in both regional and voxelwise analyses. Discussion Quantitative assessment of perceived memory functioning may be useful for screening older adults at risk for Alzheimer's disease. Individuals and their informants may provide complementary information relating to the anatomical distribution of tau.

      PubDate: 2018-04-15T16:11:10Z
      DOI: 10.1016/j.dadm.2018.03.001
       
  • Amyloid β peptides are differentially vulnerable to preanalytical surface
           exposure, an effect incompletely mitigated by the use of ratios

    • Authors: Jamie Toombs; Martha S. Foiani; Henrietta Wellington; Ross W. Paterson; Charles A. Arber; Amanda Heslegrave; Michael P. Lunn; Jonathan M. Schott; Selina Wray; Henrik Zetterberg
      Abstract: Publication date: Available online 22 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jamie Toombs, Martha S. Foiani, Henrietta Wellington, Ross W. Paterson, Charles A. Arber, Amanda Heslegrave, Michael P. Lunn, Jonathan M. Schott, Selina Wray, Henrik Zetterberg
      Introduction We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ42 alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration. Methods Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ42, Aβ40, and Aβ38 peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay. Data were analyzed using mixed models in R. Results Decrease of measurable Aβ peptide concentrations was exaggerated in longer peptides, affecting the Aβ42:Aβ40 and Aβ42:Aβ38 ratios. However, the effect size of surface treatment was reduced in Aβ peptide ratios versus Aβ42 alone. For Aβ42:Aβ40, the effect was reduced by approximately 50% (volume) and 75% (transfer) as compared to Aβ42 alone. Discussion Use of Aβ ratios, in conjunction with concentrations, may mitigate confounding factors and assist the clinical diagnostic process for Alzheimer's disease.

      PubDate: 2018-04-15T16:11:10Z
      DOI: 10.1016/j.dadm.2018.02.005
       
  • Neuropsychology and neuroimaging profiles of amyloid-positive versus
           amyloid-negative amnestic mild cognitive impairment patients

    • Authors: Clémence Tomadesso; Vincent de La Sayette; Robin de Flores; Pierrick Bourgeat; Victor L. Villemagne; Stéphanie Egret; Francis Eustache; Gaël Chételat
      Abstract: Publication date: Available online 17 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Clémence Tomadesso, Vincent de La Sayette, Robin de Flores, Pierrick Bourgeat, Victor L. Villemagne, Stéphanie Egret, Francis Eustache, Gaël Chételat
      Introduction Patients with amnestic mild cognitive impairment (aMCI) are heterogeneous as regard to their amyloid status. The present study aimed at highlighting the neuropsychological, brain atrophy, and hypometabolism profiles of amyloid-positive (Aβpos) versus amyloid-negative (Aβneg) aMCI patients. Methods Forty-four aMCI patients and 24 Aβneg healthy controls underwent neuropsychological, structural MRI, and fluoro-2-deoxy-D-glucose–positron emission tomography examinations. Data were compared between groups in specific regions of interest and voxelwise with SPM. Results When directly comparing Aβpos to Aβneg aMCI, the former had lower performances in episodic memory tests (P = .02 to P < .001) while the latter had worse scores in working memory (P = .01) and language (P < .005). Compared to Aβneg healthy controls, both aMCI subgroups showed similar profiles of atrophy and hypometabolism, with no difference between both aMCI subgroups. Conclusion In a sample of aMCI patients recruited and scanned in the same center, the main difference at baseline between Aβpos and Aβneg aMCI concerned the neuropsychological profile, but not the structural MRI or fluoro-2-deoxy-D-glucose–positron emission tomography profiles of brain alterations.

      PubDate: 2018-03-19T11:17:48Z
      DOI: 10.1016/j.dadm.2018.02.008
       
  • The personalized Alzheimer's disease cortical thickness index predicts
           likely pathology and clinical progression in mild cognitive impairment

    • Authors: Annie M. Racine; Michael Brickhouse; David A. Wolk; Bradford C. Dickerson
      Abstract: Publication date: Available online 17 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Annie M. Racine, Michael Brickhouse, David A. Wolk, Bradford C. Dickerson
      Introduction An Alzheimer's disease (AD) biomarker adjusted for age-related brain changes should improve specificity for AD-related pathological burden. Methods We calculated a brain-age-adjusted “personalized AD cortical thickness index” (pADi) in mild cognitive impairment patients from Alzheimer's Disease Neuroimaging Initiative. We performed receiver operating characteristic analysis for discrimination between patients with and without cerebrospinal fluid evidence of AD and logistic regression in an independent sample to determine if a dichotomized pADi predicted conversion to AD dementia. Results Receiver operating characteristic area under the curve was 0.69 and 0.72 in the two samples. Three empirical methods identified the same cut-point for pADi in the discovery sample. In the validation sample, 83% of pADi + mild cognitive impairment patients were cerebrospinal fluid AD biomarker positive. pADi + mild cognitive impairment patients (n = 63, 38%) were more likely to progress to AD dementia after 1 (odds ratio = 2.9) and 3 (odds ratio = 2.6) years. Discussion The pADi is a personalized, magnetic resonance imaging–derived AD biomarker that predicts progression to dementia.

      PubDate: 2018-03-19T11:17:48Z
      DOI: 10.1016/j.dadm.2018.02.007
       
  • Computer-based evaluation of AD and MCI patients during a picture
           description task

    • Authors: Laura Hernández-Domínguez; Sylvie Ratté; Gerardo Sierra-Martínez; Andrés Roche-Bergua
      Abstract: Publication date: Available online 13 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Laura Hernández-Domínguez, Sylvie Ratté, Gerardo Sierra-Martínez, Andrés Roche-Bergua
      Introduction We present a methodology to automatically evaluate the performance of patients during picture description tasks. Methods Transcriptions and audio recordings of the Cookie Theft picture description task were used. With 25 healthy elderly control (HC) samples and an information coverage measure, we automatically generated a population-specific referent. We then assessed 517 transcriptions (257 Alzheimer's disease [AD], 217 HC, and 43 mild cognitively impaired samples) according to their informativeness and pertinence against this referent. We extracted linguistic and phonetic metrics which previous literature correlated to early-stage AD. We trained two learners to distinguish HCs from cognitively impaired individuals. Results Our measures significantly (P < .001) correlated with the severity of the cognitive impairment and the Mini–Mental State Examination score. The classification sensitivity was 81% (area under the curve of receiver operating characteristics = 0.79) and 85% (area under the curve of receiver operating characteristics = 0.76) between HCs and AD and between HCs and AD and mild cognitively impaired, respectively. Dicussion An automated assessment of a picture description task could assist clinicians in the detection of early signs of cognitive impairment and AD.

      PubDate: 2018-03-19T11:17:48Z
      DOI: 10.1016/j.dadm.2018.02.004
       
  • Cross-sectional and longitudinal atrophy is preferentially associated with
           tau rather than amyloid β positron emission tomography pathology

    • Authors: Brian A. Gordon; Austin McCullough; Shruti Mishra; Tyler M. Blazey; Yi Su; John Christensen; Aylin Dincer; Kelley Jackson; Russ C. Hornbeck; John C. Morris; Beau Ances; Tammie L.S. Benzinger
      Abstract: Publication date: Available online 6 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Brian A. Gordon, Austin McCullough, Shruti Mishra, Tyler M. Blazey, Yi Su, John Christensen, Aylin Dincer, Kelley Jackson, Russ C. Hornbeck, John C. Morris, Beau Ances, Tammie L.S. Benzinger
      Introduction Structural magnetic resonance imaging is a marker of gray matter health and decline that is sensitive to impaired cognition and Alzheimer's disease pathology. Prior work has shown that both amyloid β (Aβ) and tau biomarkers are related to cortical thinning, but it is unclear what unique influences they have on the brain. Methods Aβ pathology was measured with [18F] AV-45 (florbetapir) positron emission tomography (PET) and tau was assessed with [18F] AV-1451 (flortaucipir) PET in a population of 178 older adults, of which 123 had longitudinal magnetic resonance imaging assessments (average of 5.7 years) that preceded the PET acquisitions. Results In cross-sectional analyses, greater tau PET pathology was associated with thinner cortices. When examined independently in longitudinal models, both Aβ and tau were associated with greater antecedent loss of gray matter. However, when examined in a combined model, levels of tau, but not Aβ, were still highly related to change in cortical thickness. Discussion Measures of tau PET are strongly related to gray matter atrophy and likely mediate relationships between Aβ and gray matter.

      PubDate: 2018-03-07T07:37:46Z
      DOI: 10.1016/j.dadm.2018.02.003
       
  • Regional tract-specific white matter hyperintensities are associated
           with patterns to aging-related brain atrophy via vascular risk factors,
           but also independently

    • Authors: Mohamad Habes; Guray Erus; Jon B. Toledo; Nick Bryan; Deborah Janowitz; Jimit Doshi; Henry Völzke; Ulf Schminke; Wolfgang Hoffmann; Hans J. Grabe; David A. Wolk; Christos Davatzikos
      Abstract: Publication date: Available online 5 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Mohamad Habes, Guray Erus, Jon B. Toledo, Nick Bryan, Deborah Janowitz, Jimit Doshi, Henry Völzke, Ulf Schminke, Wolfgang Hoffmann, Hans J. Grabe, David A. Wolk, Christos Davatzikos
      Introduction We sought to investigate associations of regional white matter hyperintensities (WMHs) within white matter (WM) tracts with cardiovascular risk and brain aging-related atrophy throughout adulthood in the general population, leveraging state of the art pattern analysis methods. Methods We analyzed a large sample (n = 2367) from the Study of Health in Pomerania, Germany (range 20–90 years). WMHs were automatically segmented on T1-weighted and fluid-attenuated inversion recovery magnetic resonance images, and WMH volumes were calculated in WM regions defined using the John Hopkins University WM tractography atlas. Regions with the highest average WMH volume were selected. We calculated a subject-specific index, Spatial Pattern of Alteration for Recognition of Brain Aging, to measure age-related atrophy patterns. The Framingham cardiovascular disease risk score summarized the individual cardiovascular risk profile. We used structural equation models, independently for each region, using Spatial Pattern of Alteration for Recognition of Brain Aging as a dependent variable, age as an independent variable, and cardiovascular disease risk score and regional WMH volumes as mediators. Results Selected 12 WM regions included 75% of the total WMH burden in average. Structural equation models showed that the age effect on Spatial Pattern of Alteration for Recognition of Brain Aging was mediated by WMHs to a different extent in the superior frontal WM, anterior corona radiata, inferior frontal WM, superior corona radiata, superior longitudinal fasciculus, middle temporal WM, posterior corona radiata, superior parietal WM, splenium of corpus callosum, posterior thalamic radiation, and middle occipital WM (variance explained between 2.8% and 10.3%, P < .0001 Bonferroni corrected), but not in precentral WM. Conclusions Our results indicate that WMHs, in most WM tracts, might accelerate the brain aging process throughout adulthood in the general population as a result of vascular risk factors, but also independent of them. Preventive strategies against WMHs could delay brain aging.

      PubDate: 2018-03-07T07:37:46Z
      DOI: 10.1016/j.dadm.2018.02.002
       
  • Similar pattern of atrophy in early- and late-onset AD

    • Authors: C. Eckerström; N. Klasson; E. Olsson; P. Selnes; S. Rolstad; A. Wallin
      Abstract: Publication date: Available online 1 March 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): C. Eckerström, N. Klasson, E. Olsson, P. Selnes, S. Rolstad, A. Wallin
      Background Previous research on structural changes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) have reported inconsistent findings. Material Study participants (N = 145) included 63 patients with AD, (24 patients with EOAD [aged ≤65 years], 39 patients with LOAD [aged >65 years]), 25 healthy controls aged ≤65 years, and 57 healthy controls aged >65 years. Methods In the present substudy of the Gothenburg MCI study, 1.5 T scans were used to estimate lobar and hippocampal volumes using FreeSurfer. Results Hippocampal atrophy is the most prominent feature of both EOAD and LOAD compared with controls. Direct comparison between EOAD and LOAD showed that the differences between the groups did not remain after correcting for age. Discussion Structurally, EOAD and LOAD does not seem to be different nosological entities. The difference in brain volumes between the groups compared with controls is likely due to age-related atrophy.

      PubDate: 2018-03-07T07:37:46Z
      DOI: 10.1016/j.dadm.2018.02.001
       
  • Tau positron emission tomography imaging in tauopathies: The added hurdle
           of off-target binding

    • Authors: Laetitia Lemoine; Antoine Leuzy; Konstantinos Chiotis; Elena Rodriguez-Vieitez; Agneta Nordberg
      Abstract: Publication date: Available online 23 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Laetitia Lemoine, Antoine Leuzy, Konstantinos Chiotis, Elena Rodriguez-Vieitez, Agneta Nordberg
      Ligands targeting tau for use with positron emission tomography have rapidly been developed during the past several years, enabling the in vivo study of tau pathology in patients with Alzheimer's disease and related non-Alzheimer's disease tauopathies. Several candidate compounds have been developed, showing good in vitro characteristics with respect to their ability to bind tau deposits; off-target binding, however, has also been observed. In this short commentary, we briefly summarize the available in vivo and in vitro evidence pertaining to their off-target binding and discuss the different approaches that are needed for the future development of tau positron emission tomography tracers.

      PubDate: 2018-02-26T05:51:27Z
      DOI: 10.1016/j.dadm.2018.01.007
       
  • Computer simulations for assessing cognitively intensive instrumental
           activities of daily living in older adults

    • Authors: Stephen R. Rapp; Ryan T. Barnard; Kaycee M. Sink; Dana G. Chamberlain; Valerie Wilson; Lingyi Lu; Edward H. Ip
      Abstract: Publication date: Available online 23 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Stephen R. Rapp, Ryan T. Barnard, Kaycee M. Sink, Dana G. Chamberlain, Valerie Wilson, Lingyi Lu, Edward H. Ip
      Objective To evaluate validity, reliability, diagnostic precision, and user acceptability of computer simulations of cognitively demanding tasks when administered to older adults with and without cognitive impairment. Research design and methods Five simulation modules were administered to 161 individuals aged ≥60 years with no cognitive impairment (N = 81), mild cognitive impairment (N = 52), or dementia (N = 28). Groups were compared on total accuracy and time to complete the tasks (seconds). Receiver operating characteristics were evaluated. Reliability was assessed over one month. Participants rated face validity and acceptability of each module. Results Total accuracy (P < .0001) and time (P = .0015) differed between groups. Test-retest correlations were excellent (0.79 and 0.88, respectively). Area under the curve ranged from good (0.77) to excellent (0.97). User ratings supported their face validity and acceptability. Conclusions Brief computer simulations can be useful in assessing cognitive functional abilities of older adults and distinguishing varying degrees of impairment.

      PubDate: 2018-02-26T05:51:27Z
      DOI: 10.1016/j.dadm.2018.01.008
       
  • Topographic staging of tau positron emission tomography images

    • Authors: Adam J. Schwarz; Sergey Shcherbinin; Lawrence J. Slieker; Shannon L. Risacher; Arnaud Charil; Michael C. Irizarry; Adam S. Fleisher; Sudeepti Southekal; Abhinay D. Joshi; Michael D. Devous; Bradley B. Miller; Andrew J. Saykin
      Abstract: Publication date: Available online 14 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Adam J. Schwarz, Sergey Shcherbinin, Lawrence J. Slieker, Shannon L. Risacher, Arnaud Charil, Michael C. Irizarry, Adam S. Fleisher, Sudeepti Southekal, Abhinay D. Joshi, Michael D. Devous, Bradley B. Miller, Andrew J. Saykin
      Introduction It has been proposed that the signal distribution on tau positron emission tomography (PET) images could be used to define pathologic stages similar to those seen in neuropathology. Methods Three topographic staging schemes for tau PET, two sampling the temporal and occipital subregions only and one sampling cortical gray matter across the major brain lobes, were evaluated on Flortaucipir F 18 PET images in a test-retest scenario and from Alzheimer's Disease Neuroimaging Initiative 2. Results All three schemes estimated stages that were significantly associated with amyloid status and when dichotomized to tau positive or negative were 90% to 94% concordant in the populations identified. However, the schemes with fewer regions and simpler decision rules yielded more robust performance in terms of fewer unclassified scans and increased test-retest reproducibility of assigned stage. Discussion Tau PET staging schemes could be useful tools to concisely index the regional involvement of tau pathology in living subjects. Simpler schemes may be more robust.

      PubDate: 2018-02-17T03:00:41Z
      DOI: 10.1016/j.dadm.2018.01.006
       
  • Molecular imaging: What is right and what is an illusion'

    • Authors: William E. Klunk
      Abstract: Publication date: Available online 10 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): William E. Klunk
      Over the past 40 years, brain molecular imaging has evolved from measuring cerebral metabolism with fluorodeoxyglucose, to neuroreceptor imaging, to imaging pathological protein deposits. In the early going, the characteristics of successful molecular imaging radiotracers were defined, and a detailed “Process” was developed for the collection of basic pharmacodynamic and pharmacokinetic data. These data are essential for the interpretation of in vivo imaging data and for defining the strengths, weaknesses, and limitations of new tracers. This perspective discusses the use of this “Process” in the development of the amyloid β positron emission tomography radiotracer, Pittsburgh Compound-B, and discusses some of the current controversies and difficulties in the field of tau positron emission tomography in the context of human data that preceded completion of this radiotracer characterization process—some of which still remain to be collected. As a field, we must decide which data are valid and which are artifacts and determine that when the artifacts are so overwhelming, the data are merely an illusion.

      PubDate: 2018-02-17T03:00:41Z
      DOI: 10.1016/j.dadm.2018.01.004
       
  • Elevated medial temporal lobe and pervasive brain tau-PET signal in normal
           participants

    • Authors: Val J. Lowe; Tyler J. Bruinsma; Hoon-Ki Min; Emily S. Lundt; Ping Fang; Matthew L. Senjem; Bradley F. Boeve; Keith A. Josephs; Mukesh K. Pandey; Melissa E. Murray; Kejal Kantarci; David T. Jones; Christopher G. Schwarz; David S. Knopman; Ronald C. Petersen; Clifford R. Jack
      Abstract: Publication date: Available online 7 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Val J. Lowe, Tyler J. Bruinsma, Hoon-Ki Min, Emily S. Lundt, Ping Fang, Matthew L. Senjem, Bradley F. Boeve, Keith A. Josephs, Mukesh K. Pandey, Melissa E. Murray, Kejal Kantarci, David T. Jones, Christopher G. Schwarz, David S. Knopman, Ronald C. Petersen, Clifford R. Jack
      Introduction Medial temporal lobe (MTL) uptake on tau-PET is seen not only in Alzheimer's disease (AD) dementia but also in the aging population. The relationship of these findings to the development of AD dementia needs to be better understood. Methods Tau-PET with AV-1451 was performed on 576 cognitively unimpaired (CU) participants aged 50–94 years. The number of CUs with and without abnormal MTL regions and those with or without extra-MTL abnormalities was determined. Left and right regions were compared within each subject. Results Of CUs, 58% (334/576) had abnormal tau-PET findings. MTL abnormalities were present in 41% (238/576) of subjects. Discussion MTL tau-PET signal is often associated with abnormal extra-MTL tau-PET signal in CU participants and may represent neurofibrillary tangle development that could identify participants most likely to develop AD dementia. Tau-PET signal exclusively outside of the MTL is seen in 17% of CU participants and could be the initial findings in participants in different AD dementia pathways. Significant (P < .001) differences in tau–standardized uptake value ratio between sides were noted in 26 of 41 examined brain regions implicating further study of side-specific deficits.

      PubDate: 2018-02-17T03:00:41Z
      DOI: 10.1016/j.dadm.2018.01.005
       
  • Early changes in retinal structural anatomy during the preclinical stage
           of Alzheimer's disease

    • Authors: Cláudia Y. Santos; Lenworth N. Johnson; Stuart E. Sinoff; Elena K. Festa; William C. Heindel; Peter J. Snyder
      Abstract: Publication date: Available online 7 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Cláudia Y. Santos, Lenworth N. Johnson, Stuart E. Sinoff, Elena K. Festa, William C. Heindel, Peter J. Snyder
      Introduction We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects. Methods Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline. Twenty-seven months later, they completed the same examinations and an 18F-florbetapir positron emission tomography imaging study. Results Compared to healthy control subjects, those in the preclinical stage of AD showed a significant decrease in macular retinal nerve fiber layer (mRNFL) volume, over a 27-month follow-up interval period, as well as a decrease in outer nuclear layer and inner plexiform layer volumes and thickness in the inferior quadrant. However, only the mRNFL volume was linearly related to neocortical positron emission tomography amyloid standardized uptake value ratio after controlling for any main effects of age (R 2 = 0.103; ρ = 0.017). Furthermore, the magnitude of mRNFL volume reduction was significantly correlated with performance on a task of participants' abilities to efficiently integrate visual and auditory speech information (McGurk effect). Discussion We observed a decrease in mRNFL, outer nuclear layer, and inner plexiform layer volumes, in preclinical AD relative to controls. Moreover, the largely myelinated axonal loss in the RNFL is related to increased neocortical amyloid-β accumulation after controlling for age. Volume loss in the RNFL, during the preclinical stage, is not related to performance on measures of episodic memory or problem solving. However, this retinal change does appear to be modestly related to relative decrements in performance on a measure of audiovisual integration efficiency that has been recently advanced as a possible early cognitive marker of mild cognitive impairment.

      PubDate: 2018-02-17T03:00:41Z
      DOI: 10.1016/j.dadm.2018.01.003
       
  • Moderate intensity physical activity associates with CSF biomarkers in a
           cohort at risk for Alzheimer's disease

    • Authors: Lena L. Law; Rachael N. Rol; Stephanie A. Schultz; Ryan J. Dougherty; Dorothy F. Edwards; Rebecca L. Koscik; Catherine L. Gallagher; Cynthia M. Carlsson; Barbara B. Bendlin; Henrik Zetterberg; Kaj Blennow; Sanjay Asthana; Mark A. Sager; Bruce P. Hermann; Sterling C. Johnson; Dane B. Cook; Ozioma C. Okonkwo
      Abstract: Publication date: Available online 6 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Lena L. Law, Rachael N. Rol, Stephanie A. Schultz, Ryan J. Dougherty, Dorothy F. Edwards, Rebecca L. Koscik, Catherine L. Gallagher, Cynthia M. Carlsson, Barbara B. Bendlin, Henrik Zetterberg, Kaj Blennow, Sanjay Asthana, Mark A. Sager, Bruce P. Hermann, Sterling C. Johnson, Dane B. Cook, Ozioma C. Okonkwo
      Introduction Alzheimer's disease (AD) is characterized by the presence of amyloid beta (Aβ) plaques, neurofibrillary tangles, and neurodegeneration, evidence of which may be detected in vivo via cerebrospinal fluid (CSF) sampling. Physical activity (PA) has emerged as a possible modifier of these AD-related pathological changes. Consequently, the aim of this study was to cross-sectionally examine the relationship between objectively measured PA and CSF levels of Aβ42 and tau in asymptomatic late-middle-aged adults at risk for AD. Methods Eighty-five cognitively healthy late-middle-aged adults (age = 64.31 years, 61.2% female) from the Wisconsin Registry for Alzheimer's Prevention participated in this study. They wore an accelerometer (ActiGraph GT3X+) for one week to record free-living PA, yielding measures of sedentariness and various intensities of PA (i.e., light, moderate, and vigorous). They also underwent lumbar puncture to collect CSF, from which Aβ42, total tau, and phosphorylated tau were immunoassayed. Regression analyses were used to examine the association between accelerometer measures and CSF biomarkers, adjusting for age, sex, and other relevant covariates. Results Engagement in moderate PA was associated with higher Aβ42 (P = .008), lower total tau/Aβ42 (P = .006), and lower phosphorylated tau/Aβ42 (P = .030). In contrast, neither light nor vigorous PA was associated with any of the biomarkers. Increased sedentariness was associated with reduced Aβ42 (P = .014). Conclusions In this cohort, moderate PA, but not light or vigorous, was associated with a favorable AD biomarker profile, while sedentariness was associated with greater Aβ burden. These findings suggest that a physically active lifestyle may play a protective role against the development of AD.

      PubDate: 2018-02-17T03:00:41Z
      DOI: 10.1016/j.dadm.2018.01.001
       
  • Cerebrospinal fluid and serum MHPG improve Alzheimer's disease versus
           dementia with Lewy bodies differential diagnosis

    • Authors: Jana Janssens; Yannick Vermeiren; Erik Fransen; Tony Aerts; Debby Van Dam; Sebastiaan Engelborghs; Peter P. De Deyn
      Abstract: Publication date: Available online 6 February 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jana Janssens, Yannick Vermeiren, Erik Fransen, Tony Aerts, Debby Van Dam, Sebastiaan Engelborghs, Peter P. De Deyn
      Introduction Given the challenges concerning the differential diagnosis of dementia, we investigated the possible added value of monoaminergic compounds to the standard cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Particularly, regarding the AD versus dementia with Lewy bodies (DLB) comparison, monoamines or their metabolites might have added discriminative value as there is a more severe neuropathological burden in the locus coeruleus of DLB patients, the principal site of noradrenaline synthesis. Methods We applied enzyme-linked immunosorbent assay (ELISA) to analyze CSF amyloid β peptide of 42 amino acids, total tau, and tau phosphorylated at threonine 181, in patients with AD, frontotemporal dementia, DLB/Parkinson's disease dementia, and controls. Reversed-phase high-performance liquid chromatography with electrochemical detection was implemented to study monoamine and metabolite levels in CSF and serum. Stepwise forward conditional logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic accuracy of these newly fitted models containing the most discriminative indicators of disease status. Results Most significant differences in CSF and serum were confined to the noradrenergic system. More specifically, CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were higher, whereas serum MHPG levels were lower, in DLB patients compared with all other groups. Addition of CSF and serum MHPG levels to the CSF AD biomarker panel significantly increased diagnostic accuracy between DLB/Parkinson's disease dementia and AD. Interestingly, a model only including CSF and serum MHPG without the classic AD biomarker panel reached similar area under the curve values. Discussion We hypothesize that varying degrees of neuronal loss in the locus coeruleus of DLB/Parkinson's disease dementia versus AD patients result in differentially altered MHPG levels, making this metabolite a valuable biomarker.

      PubDate: 2018-02-17T03:00:41Z
      DOI: 10.1016/j.dadm.2018.01.002
       
  • Temporal unfolding of declining episodic memory on the Free and Cued
           Selective Reminding Test in the predementia phase of Alzheimer's disease:
           Implications for clinical trials

    • Authors: Ellen Grober; Amy E. Veroff; Richard B. Lipton
      Abstract: Publication date: Available online 12 January 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Ellen Grober, Amy E. Veroff, Richard B. Lipton
      Free and Cued Selective Reminding Test performance identifies patients with preclinical disease at elevated risk for developing Alzheimer's dementia, predicting diagnosis better than other memory tests. Based on extensive literature mapping, Free and Cued Selective Reminding Test performance to clinical outcomes and biological markers and change in rates of free and total recall decline in longitudinal preclinical data, we propose five sequential stages of episodic memory decline distinguished by free and total recall score ranges and number of years before diagnosis, ending in dementia. The stages of objective memory impairment were developed using Baltimore Longitudinal Study of Aging data and replicated in the Einstein Aging Study and are intended to provide an efficient approach for clinical trial cognitive screening in advance of more costly biomarker studies and ultimately in clinical practice. Stages of objective memory impairment may provide a clinical vocabulary for understanding the pattern of Alzheimer's disease biomarkers and for reanalysis of existing clinical trial data.

      PubDate: 2018-01-25T19:39:53Z
      DOI: 10.1016/j.dadm.2017.12.004
       
  • Improving the quality of cognitive screening assessments: ACEmobile, an
           iPad-based version of the Addenbrooke's Cognitive Examination III

    • Authors: C.G.J. Newman; A. Bevins; J. Zajicek; J. Hodges; E. Vuillermoz; J. Dickenson; D. Kelly; S. Brown; R. Noad
      Abstract: Publication date: Available online 29 December 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): C.G.J. Newman, A. Bevins, J. Zajicek, J. Hodges, E. Vuillermoz, J. Dickenson, D. Kelly, S. Brown, R. Noad
      Introduction Ensuring reliable administration and reporting of cognitive screening tests are fundamental in establishing good clinical practice and research. This study captured the rate and type of errors in clinical practice, using the Addenbrooke's Cognitive Examination-III (ACE-III), and then the reduction in error rate using a computerized alternative, the ACEmobile app. Methods In study 1, we evaluated ACE-III assessments completed in National Health Service (NHS) clinics (n = 87) for administrator error. In study 2, ACEmobile and ACE-III were then evaluated for their ability to capture accurate measurement. Results In study 1, 78% of clinically administered ACE-IIIs were either scored incorrectly or had arithmetical errors. In study 2, error rates seen in the ACE-III were reduced by 85%–93% using ACEmobile. Discussion Error rates are ubiquitous in routine clinical use of cognitive screening tests and the ACE-III. ACEmobile provides a framework for supporting reduced administration, scoring, and arithmetical error during cognitive screening.

      PubDate: 2018-01-04T11:33:32Z
      DOI: 10.1016/j.dadm.2017.12.003
       
  • A novel cognitive-functional composite measure to detect changes in early
           Alzheimer's disease: Test–retest reliability and feasibility

    • Authors: Roos J. Jutten; John Harrison; Philippe R. Lee Meeuw Kjoe; Esther M. Opmeer; Niki S.M. Schoonenboom; Frank Jan de Jong; Craig W. Ritchie; Philip Scheltens; Sietske A.M. Sikkes
      Abstract: Publication date: Available online 27 December 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Roos J. Jutten, John Harrison, Philippe R. Lee Meeuw Kjoe, Esther M. Opmeer, Niki S.M. Schoonenboom, Frank Jan de Jong, Craig W. Ritchie, Philip Scheltens, Sietske A.M. Sikkes
      Introduction To improve the detection of changes in Alzheimer's disease, we designed the cognitive-functional composite (CFC). As a first validation step, we investigated its test–retest reliability and feasibility of use. Methods We performed a test–retest study with 2–3 weeks between assessments, including patients with mild cognitive impairment or mild Alzheimer's disease dementia and cognitively healthy participants. We calculated intraclass correlation coefficients type absolute agreement for all CFC measures and compared baseline and retest scores using paired sample t-tests. We evaluated feasibility by interviewing participants. Results Forty-three patients (40% female, mean age = 69.9) and 30 controls (50% female, mean age = 65) were included. Subtest intraclass correlation coefficients ranged from .70 to .96. We found negligible improvements after retesting on only two subtests. Overall, patients perceived the administration of the CFC as feasible. Conclusions The CFC is a stable and feasible measure in mild cognitive impairment and mild Alzheimer's disease, and thereby meets important quality metrics for clinically meaningful outcome measures.

      PubDate: 2018-01-04T11:33:32Z
      DOI: 10.1016/j.dadm.2017.12.002
       
  • Retinal thickness correlates with parietal cortical atrophy in EOAD and
           controls

    • Authors: Jurre den Haan; Sarah F. Janssen; Aleid van de Kreeke; Philip Scheltens; Frank Verbraak; Femke H. Bouwman
      Abstract: Publication date: Available online 6 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jurre den Haan, Sarah F. Janssen, Aleid van de Kreeke, Philip Scheltens, Frank D. Verbraak, Femke H. Bouwman
      Introduction The retina may reflect Alzheimer's disease (AD) neuropathological changes and is easily visualized with optical coherence tomography. Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid-positive early-onset AD (EOAD) patients and amyloid-negative controls. Methods We measured macular thickness and peripapillary retinal nerve fiber layer thickness with optical coherence tomography in 15 EOAD patients and 15 controls and correlated retinal thickness to visual rating scores for atrophy on magnetic resonance imaging. Results Total macular thickness correlated to parietal cortical atrophy in both groups (Spearman ρ −0.601, P = .001). Macular and peripapillary retinal nerve fiber layer thicknesses were not significantly decreased in EOAD compared to controls. Discussion Retinal thickness does not discriminate EOAD from controls but is correlated to parietal cortical atrophy in both groups. These findings may suggest reflection of cerebral cortical changes in the retina, independent of amyloid.

      PubDate: 2017-11-07T11:09:41Z
      DOI: 10.1016/j.jalz.2017.06.299
      Issue No: Vol. 13, No. 7 (2017)
       
  • Free and Cued Selective Reminding Test sensitivity

    • Authors: Raphael M. Castilhos; Marcia L. Chaves
      First page: 75
      Abstract: Publication date: 2018
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Volume 10
      Author(s): Raphael M. Castilhos, Marcia L. Chaves


      PubDate: 2017-12-16T13:49:56Z
      DOI: 10.1016/j.dadm.2017.11.005
      Issue No: Vol. 10 (2017)
       
  • Hospitalization in people with dementia with Lewy bodies: Frequency,
           duration, and cost implications

    • Authors: Christoph Mueller; Gayan Perera; Anto P. Rajkumar; Manorama Bhattarai; Annabel Price; John T. O'Brien; Clive Ballard; Robert Stewart; Dag Aarsland
      Abstract: Publication date: Available online 27 December 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Christoph Mueller, Gayan Perera, Anto P. Rajkumar, Manorama Bhattarai, Annabel Price, John T. O'Brien, Clive Ballard, Robert Stewart, Dag Aarsland
      Introduction Increased hospitalization is a major component of dementia impact on individuals and cost, but has rarely been studied in dementia with Lewy bodies (DLB). Our aim was to describe the risk and duration of hospital admissions in patients with DLB, and compare these to those in Alzheimer's disease (AD) and the general population. Methods A large database of mental health and dementia care in South London was used to assemble a cohort of patients diagnosed with DLB. These were 1:4 matched with patients diagnosed with AD on age, gender, and cognitive status. Results Rates of hospital admissions in the year after dementia diagnosis were significantly higher in 194 patients with DLB than in 776 patients with AD (crude incidence rate ratio 1.50; 95% confidence interval: 1.28–1.75) or the catchment population (indirectly standardized hospitalization rate 1.22; 95% confidence interval: 1.06–1.39). Patients with DLB had on average almost four additional hospital days per person-year than patients with AD. Multivariate Poisson regression models indicated poorer physical health early in the disease course as the main driver of this increased rate of hospitalization, whereby neuropsychiatric symptoms additionally explained the higher number of hospital days. Discussion Patients with DLB are more frequently admitted to general hospital and utilized inpatient care to a substantially higher degree than patients with AD or the general elderly population. These data highlight an opportunity to reduce hospital days by identifying DLB earlier and providing more targeted care focused on the specific triggers for hospitalization and associations of prolonged stay.

      PubDate: 2017-12-27T09:27:07Z
      DOI: 10.1016/j.dadm.2017.12.001
       
  • The Wisconsin Registry for Alzheimer's Prevention: A review of findings
           and current directions

    • Authors: Sterling Johnson; Rebecca Koscik Erin Jonaitis Lindsay Clark Kimberly Mueller
      Abstract: Publication date: Available online 8 December 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Sterling C. Johnson, Rebecca L. Koscik, Erin M. Jonaitis, Lindsay R. Clark, Kimberly D. Mueller, Sara E. Berman, Barbara B. Bendlin, Corinne D. Engelman, Ozioma C. Okonkwo, Kirk J. Hogan, Sanjay Asthana, Cynthia M. Carlsson, Bruce P. Hermann, Mark A. Sager
      The Wisconsin Registry for Alzheimer's Prevention is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer's disease (AD) dementia. Since late 2001, Wisconsin Registry for Alzheimer's Prevention has enrolled 1561 people at a mean baseline age of 54 years. Participants return for a second visit 4 years after baseline, and subsequent visits occur every 2 years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up. Serially assessed cognition, self-reported medical and lifestyle histories (e.g., diet, physical and cognitive activity, sleep, and mood), laboratory tests, genetics, and linked studies comprising molecular imaging, structural imaging, and cerebrospinal fluid data have yielded many important findings. In this cohort, PH of probable AD is associated with 46% apolipoprotein E (APOE) ε4 positivity, more than twice the rate of 22% among persons without PH. Subclinical or worse cognitive decline relative to internal normative data has been observed in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau positivity. Biomarker elevations, but not APOE or PH status, are associated with cognitive decline. Salutary health and lifestyle factors are associated with better cognition and brain structure and lower AD pathophysiologic burden. Of paramount importance is establishing the amyloid and tau AD endophenotypes to which cognitive outcomes can be linked. Such data will provide new knowledge on the early temporal course of AD pathophysiology and inform the design of secondary prevention clinical trials.

      PubDate: 2017-12-16T13:49:56Z
       
  • Microbleeds are associated with depressive symptoms in Alzheimer's disease

    • Authors: Anna E. Leeuwis; Niels D. Prins; Astrid M. Hooghiemstra; Marije R. Benedictus; Philip Scheltens; Frederik Barkhof; Wiesje M. van der Flier
      Abstract: Publication date: Available online 6 December 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Anna E. Leeuwis, Niels D. Prins, Astrid M. Hooghiemstra, Marije R. Benedictus, Philip Scheltens, Frederik Barkhof, Wiesje M. van der Flier
      Introduction Co-occurrence of cerebrovascular disease and depression led to the “vascular depression hypothesis”. White matter hyperintensities (WMHs) have been associated with depressive symptoms in population-based studies. We studied the association between small vessel disease and depressive symptoms in a memory clinic population. Methods We included >2000 patients with subjective cognitive decline (SCD), mild cognitive impairment, and Alzheimer's disease (AD). Magnetic resonance imaging was rated for WMHs, lacunes, and microbleeds. Depressive symptoms were assessed using the Geriatric Depression Scale. We performed logistic regression analysis. Results Depressive symptoms were present in AD: 17%; mild cognitive impairment: 25%; and SCD: 23%. SCD patients with WMHs showed higher propensity of depressive symptoms than AD patients with WMHs. AD patients with microbleeds were more likely to have depressive symptoms compared with AD patients without microbleeds (odds ratio = 1.70; 95% confidence interval: 1.08–2.68). Discussion Microbleeds are associated with depressive symptoms in AD, supporting a potential role of cerebral amyloid angiopathy in the occurrence of depressive symptoms in AD.

      PubDate: 2017-12-16T13:49:56Z
      DOI: 10.1016/j.dadm.2017.11.006
       
  • The relationship between recall of recently versus remotely encoded famous
           faces and amyloidosis in clinically normal older adults

    • Authors: Irina Orlovsky; Willem Huijbers; Bernard Hanseeuw; Elizabeth Mormino; Trey Hedden; Rachel F. Buckley; Molly LaPoint; Jennifer Rabin; Dorene M. Rentz; Keith A. Johnson; Reisa A. Sperling; Kathryn V. Papp
      Abstract: Publication date: Available online 23 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Irina Orlovsky, Willem Huijbers, Bernard Hanseeuw, Elizabeth Mormino, Trey Hedden, Rachel F. Buckley, Molly LaPoint, Jennifer Rabin, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, Kathryn V. Papp
      Introduction Alzheimer's disease (AD) patients exhibit temporally graded memory loss with remote memories remaining more intact than recent memories. It is unclear whether this temporal pattern is observable in clinically normal adults with amyloid pathology (i.e. preclinical AD). Methods Participants were asked to recall the names of famous figures who are most prominent recently (famous after 1990) and remotely (famous from 1960–1980) and were provided with a phonemic cue to ensure that memory failure was not purely due to verbal retrieval weaknesses. In addition, participants identified line drawings of objects. Clinically normal older adults (n = 125) were identified as amyloid β positive or negative (Aβ+/−) using Pittsburgh compound B positron emission tomography. The relationship between Aβ+/− and recall of remote and recent famous face-names and objects was examined using repeated measures analyses and general linear models controlling for demographics and media usage. Results When provided with a phonemic cue, Aβ+ participants recalled the names of fewer recent famous faces compared with Aβ− participants. However, recall of remote famous face-names and objects did not differ by Aβ group. Discussion Relative sparing of remotely learned information compared with recently learned information is (1) detectable in the preclinical stages of AD and (2) related to amyloid pathology. Both temporal gradient and person-centered assessment rather than object-centered semantic information may be particularly meaningful for tracking early memory changes in the AD trajectory.

      PubDate: 2017-12-16T13:49:56Z
      DOI: 10.1016/j.dadm.2017.11.003
       
  • Type 2 diabetes mellitus and cerebrospinal fluid Alzheimer's disease
           biomarker amyloid β1-42 in Alzheimer's Disease Neuroimaging Initiative
           participants

    • Authors: Wei Li; Shannon L. Risacher; Sujuan Gao; Stephen L. Boehm; Jeffrey S. Elmendorf; Andrew J. Saykin
      Abstract: Publication date: Available online 23 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Wei Li, Shannon L. Risacher, Sujuan Gao, Stephen L. Boehm, Jeffrey S. Elmendorf, Andrew J. Saykin
      Introduction Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease. Cerebrospinal fluid (CSF) amyloid β (Aβ) 1-42 is an important Alzheimer's disease biomarker. However, it is inconclusive on how T2DM is related to CSF Aβ1-42. Methods Participants with T2DM were selected from the Alzheimer's Disease Neuroimaging Initiative by searching keywords from the medical history database. A two-way analysis of covariance model was used to analyze how T2DM associates with CSF Aβ1-42 or cerebral cortical Aβ. Results CSF Aβ1-42 was higher in the T2DM group than the nondiabetic group. The inverse relation between CSF Aβ1-42 and cerebral cortical Aβ was independent of T2DM status. Participants with T2DM had a lower cerebral cortical Aβ in anterior cingulate, precuneus, and temporal lobe than controls. Discussion T2DM is positively associated with CSF Aβ1-42 but negatively with cerebral cortical Aβ. The decreased cerebral cortical Aβ associated with T2DM is preferentially located in certain brain regions.

      PubDate: 2017-12-16T13:49:56Z
      DOI: 10.1016/j.dadm.2017.11.002
       
  • Monoaminergic impairment in Down syndrome with Alzheimer's disease
           compared to early-onset Alzheimer's disease

    • Authors: Alain D. Dekker; Yannick Vermeiren; Maria Carmona-Iragui; Bessy Benejam; Laura Videla; Ellen Gelpi; Tony Aerts; Debby Van Dam; Susana Fernández; Alberto Lleó; Sebastian Videla; Anne Sieben; Jean-Jacques Martin; Rafael Blesa; Juan Fortea; Peter P. De Deyn
      Abstract: Publication date: Available online 23 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Alain D. Dekker, Yannick Vermeiren, Maria Carmona-Iragui, Bessy Benejam, Laura Videla, Ellen Gelpi, Tony Aerts, Debby Van Dam, Susana Fernández, Alberto Lleó, Sebastian Videla, Anne Sieben, Jean-Jacques Martin, Rafael Blesa, Juan Fortea, Peter P. De Deyn
      Introduction People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS. Methods Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol; dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n = 4), DS with AD (DS+AD, n = 17), early-onset AD (EOAD, n = 11) patients, and healthy non-DS controls (n = 10) in the general population. Moreover, monoaminergic concentrations were determined in cerebrospinal fluid (CSF)/plasma samples of DS (n = 37/149), DS with prodromal AD (DS+pAD, n = 13/36), and DS+AD (n = 18/40). Results In brain, noradrenergic and serotonergic compounds were overall reduced in DS+AD versus EOAD, while the dopaminergic system showed a bidirectional change. For DS versus non-DS controls, significantly decreased 3-methoxy-4-hydroxyphenylglycol levels were noted in various brain regions, though to a lesser extent than for DS+AD versus EOAD. Apart from 3,4-dihydroxyphenylacetic acid, CSF/plasma concentrations were not altered between groups. Discussion Monoamine neurotransmitters and metabolites were evidently impacted in DS, DS+AD, and EOAD. DS and DS+AD presented a remarkably similar monoaminergic profile, possibly related to early deposition of amyloid pathology in DS. To confirm whether monoaminergic alterations are indeed due to early amyloid-β accumulation, future avenues include positron emission tomography studies of monoaminergic neurotransmission in relation to amyloid deposition, as well as relating monoaminergic concentrations to CSF/plasma levels of amyloid-β and tau within individuals.

      PubDate: 2017-12-16T13:49:56Z
      DOI: 10.1016/j.dadm.2017.11.001
       
  • Letter

    • Authors: Ara Khachaturian
      Abstract: Publication date: 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Volume 9
      Author(s): Ara S. Khachaturian


      PubDate: 2017-12-16T13:49:56Z
       
  • Continuous measurement of object location memory is sensitive to effects
           of age and mild cognitive impairment and related to medial temporal lobe
           volume

    • Authors: Benjamin M. Hampstead; Stephen Towler; Anthony Y. Stringer; K. Sathian
      Abstract: Publication date: Available online 11 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Benjamin M. Hampstead, Stephen Towler, Anthony Y. Stringer, K. Sathian
      Introduction We present findings of a novel and ecologically relevant associative memory test, the Object Location Touchscreen Test (OLTT), which was posited as sensitive to early medial temporal lobe compromise associated with mild cognitive impairment (MCI). Methods A total of 114 participants, including healthy young and older controls and patients with MCI, completed the OLTT and standard neuropsychological testing. The OLTT required participants to recall the location of objects under free and cued recall conditions, with accuracy evaluated using distance measures (i.e., a continuous error score), and a standard recognition format. Correlations between performance and volumetric data were evaluated from a subset of 77 participants. Results Significant age effects were dwarfed by MCI effects across all test conditions. OLTT Cued Recall was strongly and specifically related to the integrity of disease-relevant medial temporal lobe regions, generally more than traditional memory tests. Discussion The OLTT may be sensitive to early structural compromise in regions affected by Alzheimer's disease.

      PubDate: 2017-11-14T13:02:26Z
      DOI: 10.1016/j.dadm.2017.10.007
       
  • White matter signal abnormalities in former National Football League
           players

    • Authors: Michael L. Alosco; Inga K. Koerte; Yorghos Tripodis; Megan Mariani; Alicia S. Chua; Johnny Jarnagin; Yashar Rahimpour; Christian Puzo; Rose C. Healy; Brett Martin; Christine E. Chaisson; Robert C. Cantu; Rhoda Au; Michael McClean; Ann C. McKee; Alexander P. Lin; Martha E. Shenton; Ronald J. Killiany; Robert A. Stern
      Abstract: Publication date: Available online 6 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Michael L. Alosco, Inga K. Koerte, Yorghos Tripodis, Megan Mariani, Alicia S. Chua, Johnny Jarnagin, Yashar Rahimpour, Christian Puzo, Rose C. Healy, Brett Martin, Christine E. Chaisson, Robert C. Cantu, Rhoda Au, Michael McClean, Ann C. McKee, Alexander P. Lin, Martha E. Shenton, Ronald J. Killiany, Robert A. Stern
      Introduction Later-life brain alterations in former tackle football players are poorly understood, particularly regarding their relationship with repetitive head impacts (RHIs) and clinical function. We examined white matter signal abnormalities (WMSAs) and their association with RHIs and clinical function in former National Football League (NFL) players. Methods Eighty-six clinically symptomatic former NFL players and 23 same-age reportedly asymptomatic controls without head trauma exposure underwent magnetic resonance imaging and neuropsychological testing. FreeSurfer calculated WMSAs. A cumulative head impact index quantified RHIs. Results In former NFL players, increased volume of WMSAs was associated with higher cumulative head impact index scores (P = .043) and worse psychomotor speed and executive function (P = .015). Although former NFL players had greater WMSA volume than controls (P = .046), these findings are inconclusive due to recruitment of controls based on lack of clinical symptoms and head trauma exposure. Discussion In former NFL players, WMSAs may reflect long-term microvascular and nonmicrovascular pathologies from RHIs that negatively impact cognition.

      PubDate: 2017-11-07T11:09:41Z
      DOI: 10.1016/j.dadm.2017.10.003
       
  • Lower cerebral blood flow in subjects with Alzheimer's dementia, mild
           cognitive impairment, and subjective cognitive decline using 2D
           phase-contrast MRI

    • Authors: Jolien F. Leijenaar; Ingrid S. van Maurik; Joost P.A. Kuijer; Wiesje M. van der Flier; Philip Scheltens; Frederik Barkhof; Niels D. Prins
      Abstract: Publication date: Available online 2 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jolien F. Leijenaar, Ingrid S. van Maurik, Joost P.A. Kuijer, Wiesje M. van der Flier, Philip Scheltens, Frederik Barkhof, Niels D. Prins
      Introduction In this cross-sectional study, we aimed to detect differences in cerebral blood flow (CBF) between subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD), using two-dimensional phase-contrast magnetic resonance imaging. Methods We included 74 AD patients (67 years, 51% female), 36 MCI patients (66 years, 33% female), and 62 patients (60 years, 32% female) with SCD from the Amsterdam Dementia Cohort. Patients with SCD are those who visited the memory clinic with subjective cognitive complaints without objective cognitive impairment. Whole-brain CBF (mL/100 g/min) was calculated using total volume flow measured with two-dimensional phase-contrast magnetic resonance imaging and normalized for brain volume. Results Mean CBF values (SD) were lower in AD compared with SCD (age and sex adjusted 70 ± 26 vs. 82 ± 24 mL/100 g/min, P < .05). Mean CBF values of MCI were comparable to AD. Across clinical groups, lower CBF was associated with lower scores on the Mini–Mental State Examination (age and sex adjusted stβ = 0.19 per mL/100 g/min; P = .02). Discussion Lower whole-brain CBF is seen in AD patients compared with SCD patients and is associated with worse cognitive function.

      PubDate: 2017-11-07T11:09:41Z
      DOI: 10.1016/j.dadm.2017.10.001
       
  • Probability of Alzheimer's disease in breast cancer survivors based on
           gray-matter structural network efficiency

    • Authors: Shelli R. Kesler; Vikram Rao; William J. Ray; Arvind Rao
      Abstract: Publication date: Available online 1 November 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Shelli R. Kesler, Vikram Rao, William J. Ray, Arvind Rao
      Introduction Breast cancer chemotherapy is associated with accelerated aging and potentially increased risk for Alzheimer's disease (AD). Methods We calculated the probability of AD diagnosis from brain network and demographic and genetic data obtained from 47 female AD converters and 47 matched healthy controls. We then applied this algorithm to data from 78 breast cancer survivors. Results The classifier discriminated between AD and healthy controls with 86% accuracy (P < .0001). Chemotherapy-treated breast cancer survivors demonstrated significantly higher probability of AD compared to healthy controls (P < .0001) and chemotherapy-naïve survivors (P = .007), even after stratifying for apolipoprotein e4 genotype. Chemotherapy-naïve survivors also showed higher AD probability compared to healthy controls (P = .014). Discussion Chemotherapy-treated breast cancer survivors who have a particular profile of brain structure may have a higher risk for AD, especially those who are older and have lower cognitive reserve.

      PubDate: 2017-11-07T11:09:41Z
      DOI: 10.1016/j.dadm.2017.10.002
       
  • Long-term impact of intensive lifestyle intervention on cognitive function
           assessed with the NIH toolbox: The Look AHEAD study

    • Authors: Kathleen M. Hayden; Laura D. Baker; George Bray; Raymond Carvajal; Kathryn Demos-McDermott; Andrea L. Hergenroeder; James O. Hill; Edward Horton; John M. Jakicic; Karen C. Johnson; Rebecca H. Neiberg; Stephen R. Rapp; Thomas A. Wadden; Michael E. Miller
      Abstract: Publication date: Available online 9 October 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Kathleen M. Hayden, Laura D. Baker, George Bray, Raymond Carvajal, Kathryn Demos-McDermott, Andrea L. Hergenroeder, James O. Hill, Edward Horton, John M. Jakicic, Karen C. Johnson, Rebecca H. Neiberg, Stephen R. Rapp, Thomas A. Wadden, Michael E. Miller
      Introduction To determine whether 10 years of assignment to intensive lifestyle intervention (ILI) relative to diabetes support and education leads to better cognition. We examine intervention effects overall and among clinical subgroups, and report correlations between computer-administered and interviewer-administered cognitive batteries. Methods The Action for Health in Diabetes (Look AHEAD) was a 16-site randomized controlled trial with overweight/obese individuals (aged 45–76) who had type 2 diabetes. The NIH Toolbox Cognition Battery tests developed to measure cognition across the lifespan were used to evaluate cognition. Results were compared with standard paper-and-pencil tests. The Toolbox and paper-and-pencil tests were administered an average of 10.9 years after randomization to 1002 participants. Results Toolbox measures significantly correlated with interviewer-administered measures, with the strongest correlations between the Toolbox Fluid Cognition Composite and Trails B (r = −0.64, P < .0001) and Digit Symbol Coding (r = 0.63, P < .0001), and between the Toolbox Dimensional Change Card Sort (r = 0.55, P < .0001) and the Digit Symbol Coding test. Overall, ILI and diabetes support and education groups had similar adjusted mean cognitive outcomes (P > .05 for all). Subgroup analyses identified different intervention effects within baseline body mass index groups for Picture Sequence Memory (P = .01), within baseline cardiovascular disease groups for Picture Vocabulary (P = .01) and Fluid Cognition Composite (P = .02) measures, and within baseline age groups for Picture Vocabulary (P = .02). Discussion Correlations between Toolbox and interviewer-administered outcomes provide a measure of internal validity. Findings suggest no overall effect of the intervention on cognition and that an ILI resulting in weight loss may have negative implications for cognition in individuals aged ≥60, with previous history of cardiovascular disease, and those with body mass index ≥40.

      PubDate: 2017-10-13T23:55:14Z
      DOI: 10.1016/j.dadm.2017.09.002
       
  • Olfactory identification in subjective cognitive decline and mild
           cognitive impairment: Association with tau but not amyloid positron
           emission tomography

    • Authors: Shannon L. Risacher; Eileen F. Tallman; John D. West; Karmen K. Yoder; Gary D. Hutchins; James W. Fletcher; Sujuan Gao; David A. Kareken; Martin R. Farlow; Liana G. Apostolova; Andrew J. Saykin
      Abstract: Publication date: Available online 23 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Shannon L. Risacher, Eileen F. Tallman, John D. West, Karmen K. Yoder, Gary D. Hutchins, James W. Fletcher, Sujuan Gao, David A. Kareken, Martin R. Farlow, Liana G. Apostolova, Andrew J. Saykin
      Introduction We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration. Methods Thirty-four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel-wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD. Results Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel-wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT. Discussion Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease.

      PubDate: 2017-09-30T16:03:14Z
      DOI: 10.1016/j.dadm.2017.09.001
       
  • Further education improves cognitive reserve and triggers improvement in
           selective cognitive functions in older adults: The Tasmanian Healthy Brain
           Project

    • Authors: Megan E. Thow; Mathew J. Summers; Nichole L. Saunders; Jeffery J. Summers; Karen Ritchie; James C. Vickers
      Abstract: Publication date: Available online 19 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Megan E. Thow, Mathew J. Summers, Nichole L. Saunders, Jeffery J. Summers, Karen Ritchie, James C. Vickers
      Introduction The strong link between early-life education and subsequent reduced risk of dementia suggests that education in later life could enhance cognitive function and may reduce age-related cognitive decline and protect against dementia. Methods Episodic memory, working memory, executive function, and language processing performances were assessed annually over 4 years in 359 healthy older adults who attended university for a minimum of 12 months (intervention) and were compared against 100 healthy adult controls. Results Multiple group latent growth curve modeling revealed a significant improvement in language processing capacity over time in the intervention group. No changes were detected for episodic memory, working memory, or executive function. Discussion These results suggest that complex mental stimulation resulting from late-life further education results in improved crystallized knowledge but no changes to fluid cognitive functions.

      PubDate: 2017-09-23T13:20:57Z
      DOI: 10.1016/j.dadm.2017.08.004
       
  • Analysis of macrolinguistic aspects of narratives from individuals with
           Alzheimer's disease, mild cognitive impairment, and no cognitive
           impairment

    • Authors: Cíntia Matsuda Toledo; Sandra Maria Aluísio; Leandro Borges do Santos; Sonia Maria Dozzi Brucki; Eduardo Sturzeneker Trés; Maira Okada de Oliveira; Letícia Lessa Mansur
      Abstract: Publication date: Available online 19 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Cíntia Matsuda Toledo, Sandra Maria Aluísio, Leandro Borges do Santos, Sonia Maria Dozzi Brucki, Eduardo Sturzeneker Trés, Maira Okada de Oliveira, Letícia Lessa Mansur
      Introduction The depiction of features in discourse production promotes accurate diagnosis and helps to establish the therapeutic intervention in cognitive impairment and dementia. We aimed to identify alterations in the macrolinguistic aspects of discourse using a new computational tool. Methods Sixty individuals, aged 60 years and older, were distributed in three different groups: mild Alzheimer's disease (mAD), amnestic mild cognitive impairment, and healthy controls. A narrative created by individuals was analyzed through the Coh-Metrix-Dementia program, extracting the features of interest automatically. Results mAD showed worse overall performance compared to the other groups: less informative discourse, greater impairment in global coherence, greater modalization, and inferior narrative structure. It was not possible to discriminate between amnestic mild cognitive impairment and healthy controls. Discussion Our results are in line with the literature, verifying a pathological change in the macrostructure of discourse in mAD.

      PubDate: 2017-09-23T13:20:57Z
      DOI: 10.1016/j.dadm.2017.08.005
       
  • The effects of apolipoprotein E genotype, α-synuclein deficiency, and sex
           on brain synaptic and Alzheimer's disease–related pathology

    • Authors: Roni Bar; Anat Boehm-Cagan; Ishai Luz; Yarden Kleper-Wall; Daniel M. Michaelson
      Abstract: Publication date: Available online 6 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Roni Bar, Anat Boehm-Cagan, Ishai Luz, Yarden Kleper-Wall, Daniel M. Michaelson
      Introduction Alzheimer's disease (AD) and synucleinopathies share common pathologic mechanisms. Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, also increases the risk for dementia in pure synucleinopathies. We presently examined the effects of α-synuclein deficiency (α-syn−/−) and sex on apoE4-driven pathologies. Methods AD-related, synaptic, and vascular markers were analyzed in female and male α-syn−/− and α-syn+/+ apoE4, apoE3, and apoE3/E4 mice. Results ApoE4 was hypolipidated, and this effect was unchanged by α-syn−/− and sex. The levels of synaptic markers were lower, and the levels of AD-related parameters were higher in female α-syn−/− apoE4 mice compared with the corresponding apoE3 mice. By comparison, apoE4 had small effects on the AD parameters of male and female α-syn+/+ apoE4 mice. Discussion Although α-syn−/− does not affect the upstream lipidation impairment of apoE4, it acts as a “second hit” enhancer of the subsequent apoE4-driven pathologies.

      PubDate: 2017-09-11T11:15:30Z
      DOI: 10.1016/j.dadm.2017.08.003
       
  • Effect of apolipoprotein E phenotype on the association of plasma
           beta-amyloid and amyloid positron emission tomography imaging in Japan

    • Authors: Amane Tateno; Takeshi Sakayori; Woo Chan Kim; Michihiko Koeda; Shinichiro Kumita; Hidenori Suzuki; Yoshiro Okubo
      Abstract: Publication date: Available online 5 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Amane Tateno, Takeshi Sakayori, Woo Chan Kim, Michihiko Koeda, Shinichiro Kumita, Hidenori Suzuki, Yoshiro Okubo
      Introduction The plasma concentration of beta-amyloid (Aβ) has been considered another biomarker of Alzheimer's disease and was reportedly associated with cortical Aβ accumulation. Methods We analyzed 28 subjects with apolipoprotein E4 (ApoE4; E4 group) and 89 subjects without ApoE4 (non-E4 group) to determine the association between cortical Aβ accumulation by standard uptake value ratio with [18F]florbetapir positron emission tomography and plasma Aβ1–40 and Aβ1–42. Results Aβ1–42/Aβ1–40 correlated significantly with mean regional [18F]florbetapir standard uptake value ratio in the non-E4 group (R 2 = 0.06, P = .02) but not in the E4 group, and receiver operating characteristic curve analysis for Aβ1–42/Aβ1–40 in the non-E4 group showed sensitivity (92.9%) and specificity (45.9%) with a cutoff value of 0.150 for Aβ positivity. Discussion We verified that the correlation between Aβ1–42/Aβ1–40 and Aβ accumulation differed according to ApoE phenotype. The high sensitivity of plasma Aβ1–42/Aβ1–40 for Aβ positivity in non-E4 subjects indicated a possible role of plasma Aβ1–42/Aβ1–40 as a screening biomarker before amyloid positron emission tomography in clinical settings.

      PubDate: 2017-09-06T09:53:01Z
      DOI: 10.1016/j.dadm.2017.08.002
       
  • Characterizing biomarker features of cognitively normal individuals with
           ventriculomegaly

    • Authors: Xiaofeng Li; Maowen Ba; Kok Pin Ng; Sulantha Mathotaarachchi; Tharick A. Pascoal; Pedro Rosa-Neto; Serge Gauthier
      Abstract: Publication date: Available online 5 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Xiaofeng Li, Maowen Ba, Kok Pin Ng, Sulantha Mathotaarachchi, Tharick A. Pascoal, Pedro Rosa-Neto, Serge Gauthier
      Introduction The clinical significance of ventriculomegaly in cognitively normal elderly individuals remains unclear. Methods We selected cognitively normal individuals (n = 425) from the Alzheimer's Disease Neuroimaging Initiative database and calculated Evans index (EI) based on the ratio of the frontal horn and skull diameter. We defined ventriculomegaly as EI ≥ 0.30, and the participants were stratified into EI ≥ 0.30 group and EI < 0.30 group. Neuropsychological, imaging, and fluid biomarker profiles between the two groups were then compared using regression models. Results A total of 96 (22.5%) individuals who had ventriculomegaly performed worse on the cognitive tests; showed smaller hippocampal volume but larger caudate, cingulate, and paracentral gyrus volumes; and displayed lower positron emission tomography [18F]fluorodeoxyglucose standardized uptake value ratio but higher amyloid burden represented by higher [18F]florbetapir standardized uptake value ratio and lower cerebrospinal fluid amyloid β 1–42 levels compared to those without ventriculomegaly. Discussion Asymptomatic ventriculomegaly might be an early imaging signature of preclinical Alzheimer's disease and/or normal pressure hydrocephalus.

      PubDate: 2017-09-06T09:53:01Z
      DOI: 10.1016/j.dadm.2017.08.001
       
  • Entorhinal and transentorhinal atrophy in mild cognitive impairment using
           longitudinal diffeomorphometry

    • Authors: Daniel J. Tward; Chelsea S. Sicat; Timothy Brown; Arnold Bakker; Michela Gallagher; Marilyn Albert; Michael Miller
      Abstract: Publication date: Available online 30 August 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Daniel J. Tward, Chelsea S. Sicat, Timothy Brown, Arnold Bakker, Michela Gallagher, Marilyn Albert, Michael Miller
      Introduction Autopsy findings have shown the entorhinal cortex and transentorhinal cortex are among the earliest sites of accumulation of pathology in patients developing Alzheimer's disease. Methods Here, we study this region in subjects with mild cognitive impairment (n = 36) and in control subjects (n = 16). The cortical areas are manually segmented, and local volume and shape changes are quantified using diffeomorphometry, including a novel mapping procedure that reduces variability in anatomic definitions over time. Results We find significant thickness and volume changes localized to the transentorhinal cortex through high field strength atlasing. Discussion This demonstrates that in vivo neuroimaging biomarkers can detect these early changes among subjects with mild cognitive impairment.

      PubDate: 2017-09-06T09:53:01Z
      DOI: 10.1016/j.dadm.2017.07.005
       
  • Regional tau deposition and subregion atrophy of medial temporal
           structures in early Alzheimer's disease: A combined positron emission
           tomography/magnetic resonance imaging study

    • Authors: Daichi Sone; Etsuko Imabayashi; Norihide Maikusa; Nobuyuki Okamura; Shozo Furumoto; Yukitsuka Kudo; Masayo Ogawa; Harumasa Takano; Yuma Yokoi; Masuhiro Sakata; Tadashi Tsukamoto; Koichi Kato; Hiroshi Matsuda
      Abstract: Publication date: Available online 4 August 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Daichi Sone, Etsuko Imabayashi, Norihide Maikusa, Nobuyuki Okamura, Shozo Furumoto, Yukitsuka Kudo, Masayo Ogawa, Harumasa Takano, Yuma Yokoi, Masuhiro Sakata, Tadashi Tsukamoto, Koichi Kato, Hiroshi Matsuda
      Introduction Molecular imaging and selective hippocampal subfield atrophy are a focus of recent Alzheimer's disease (AD) research. Here, we investigated correlations between molecular imaging and hippocampal subfields in early AD. Methods We investigated 18 patients with early AD and 18 healthy control subjects using 11C-PIB positron emission tomography (PET) and 18F-THK5351 PET and automatic segmentation of hippocampal subfields with high-resolution T2-weighted magnetic resonance imaging. The PET images were normalized and underwent voxelwise regression analysis with each subregion volumes using SPM12. Results As for 18F-THK5351 PET, the bilateral perirhinal cortex volumes were significantly associated with the ipsilateral or bilateral temporal lobar uptakes, whereas hippocampal subfields showed no correlations. 11C-PIB PET showed relatively broad negative correlation with the right cornu ammonis A3 volumes. Discussion Regional tau deposition was correlated with extrahippocampal subregional atrophy and not with hippocampal subfields, possibly reflecting different underlying mechanisms of atrophy in early AD. Amyloid might be associated with right cornu ammonis 3 atrophy.

      PubDate: 2017-08-08T23:36:11Z
      DOI: 10.1016/j.dadm.2017.07.001
       
  • Performance of [18F]flutemetamol amyloid imaging against the neuritic
           plaque component of CERAD and the current (2012) NIA-AA recommendations
           for the neuropathologic diagnosis of Alzheimer's disease

    • Authors: Stephen Salloway; Jose E. Gamez; Upinder Singh; Carl H. Sadowsky; Teresa Villena; Marwan N. Sabbagh; Thomas G. Beach; Ranjan Duara; Adam S. Fleisher; Kirk A. Frey; Zuzana Walker; Arvinder Hunjan; Yavir M. Escovar; Marc E. Agronin; Joel Ross; Andrea Bozoki; Mary Akinola; Jiong Shi; Rik Vandenberghe; Milos D. Ikonomovic; Paul F. Sherwin; Gill Farrar; Adrian P.L. Smith; Christopher J. Buckley; Dietmar Rudolf Thal; Michelle Zanette; Craig Curtis
      Abstract: Publication date: Available online 1 July 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Stephen Salloway, Jose E. Gamez, Upinder Singh, Carl H. Sadowsky, Teresa Villena, Marwan N. Sabbagh, Thomas G. Beach, Ranjan Duara, Adam S. Fleisher, Kirk A. Frey, Zuzana Walker, Arvinder Hunjan, Yavir M. Escovar, Marc E. Agronin, Joel Ross, Andrea Bozoki, Mary Akinola, Jiong Shi, Rik Vandenberghe, Milos D. Ikonomovic, Paul F. Sherwin, Gill Farrar, Adrian P.L. Smith, Christopher J. Buckley, Dietmar Rudolf Thal, Michelle Zanette, Craig Curtis
      Introduction Performance of the amyloid tracer [18F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD “original” and “modified” and the amyloid component of the 2012 NIA-AA guidelines). Methods After [18F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures. Results By SoT, sensitivity and specificity of majority image interpretations were, respectively, 91.9% and 87.5% with “original CERAD,” 90.8% and 90.0% with “modified CERAD,” and 85.7% and 100% with the 2012 NIA-AA criteria. Discussion The high accuracy of either CERAD criteria suggests that [18F]flutemetamol predominantly reflects neuritic amyloid plaque density. However, the use of CERAD criteria as the SoT can result in some false-positive results because of the presence of diffuse plaques, which are accounted for when the positron emission tomography read is compared with the 2012 NIA-AA criteria.

      PubDate: 2017-07-04T07:27:20Z
      DOI: 10.1016/j.dadm.2017.06.001
       
  • Assessment of β-amyloid in pathologically confirmed frontotemporal
           dementia syndromes

    • Authors: Rachel H. Tan; Jillian J. Kril; Yue Yang; Nicole Tom; John R. Hodges; Victor L. Villemagne; Christopher C. Rowe; Cristian E. Leyton; John B.J. Kwok; Lars M. Ittner; Glenda M. Halliday
      Abstract: Publication date: Available online 29 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Rachel H. Tan, Jillian J. Kril, Yue Yang, Nicole Tom, John R. Hodges, Victor L. Villemagne, Christopher C. Rowe, Cristian E. Leyton, John B.J. Kwok, Lars M. Ittner, Glenda M. Halliday
      Introduction The diagnostic utility of in vivo β-amyloid imaging to aid in the clinical distinction between frontotemporal dementia (FTD) and Alzheimer's disease remains unclear without data on the prevalence and severity of β-amyloid in pathologically confirmed FTD syndromes. Methods β-amyloid was assessed in 98 autopsy-confirmed FTD and 36 control cases, and the pathological accuracy of 11C-Pittsburgh compound B (PiB)–positron emission tomography imaging was assessed in a subset of FTD cases (n = 15). Results β-amyloid was identified in a similar proportion of FTD syndromes and age-matched controls and increases with age. Alzheimer's disease pathology was identified in all cases with high PiB retention and in one case with low PiB retention. We further demonstrate a strong regional correlation between volume fraction of histological β-amyloid with PiB standard uptake value ratio scaled to the white matter. Discussion The present study provides a pathologic reference to assist in the interpretation of in vivo assessments in FTD syndromes.

      PubDate: 2017-06-03T22:51:02Z
      DOI: 10.1016/j.dadm.2017.05.005
       
  • Longitudinal changes in amyloid positron emission tomography and
           volumetric magnetic resonance imaging in the nondemented Down syndrome
           population

    • Authors: Patrick J. Lao; Ben L. Handen; Tobey J. Betthauser; Iulia Mihaila; Sigan L. Hartley; Annie D. Cohen; Dana L. Tudorascu; Peter D. Bulova; Brian J. Lopresti; Rameshwari V. Tumuluru; Dhanabalan Murali; Chester A. Mathis; Todd E. Barnhart; Charles K. Stone; Julie C. Price; Darlynne A. Devenny; Marsha R. Mailick; William E. Klunk; Sterling C. Johnson; Bradley T. Christian
      Abstract: Publication date: Available online 23 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Patrick J. Lao, Ben L. Handen, Tobey J. Betthauser, Iulia Mihaila, Sigan L. Hartley, Annie D. Cohen, Dana L. Tudorascu, Peter D. Bulova, Brian J. Lopresti, Rameshwari V. Tumuluru, Dhanabalan Murali, Chester A. Mathis, Todd E. Barnhart, Charles K. Stone, Julie C. Price, Darlynne A. Devenny, Marsha R. Mailick, William E. Klunk, Sterling C. Johnson, Bradley T. Christian
      Introduction Down syndrome (DS) arises from a triplication of chromosome 21, causing overproduction of the amyloid precursor protein and predisposes individuals to early Alzheimer's disease (AD). Methods Fifty-two nondemented adults with DS underwent two cycles of carbon 11-labeled Pittsburgh compound B ([11C]PiB) and T1wMRI scans 3.0 ± 0.6 years apart. Standard uptake value ratio (SUVR) images (50–70 minutes; cerebellar gray matter [GM]) and GM volumes were analyzed in standardized space (MNI). Results 85% of PiB(−) subjects remained PiB(−), whereas 15% converted to PiB(+), predominantly in the striatum. None reverted from PiB(+) to PiB(−). Increases in SUVR were distributed globally, but there were no decreases in GM volume. The PiB positivity groups differed in the percent rate of change in SUVR [PiB(−): 0.5%/year, PiB converters: 4.9%/year, and PiB(+): 3.7%/year], but not in GM volume. Discussion Despite the characteristic striatum-first pattern, the global rate of amyloid accumulation differs by pre-existing amyloid burden and precedes atrophy or dementia in the DS population, similar to general AD progression.

      PubDate: 2017-05-24T19:30:22Z
      DOI: 10.1016/j.dadm.2017.05.001
       
  • Changes in metabolic risk factors over 10 years and their associations
           with late-life cognitive performance: The Multi-Ethnic Study of
           Atherosclerosis

    • Authors: Timothy M. Hughes; Suzanne Craft; Laura Baker; Mark A. Espeland; Stephen R. Rapp; Kaycee M. Sink; Alain G. Bertoni; Gregory L. Burke; Rebecca F. Gottesman; Erin D. Michos; José A. Luchsinger; Annette L. Fitzpatrick; Kathleen M. Hayden
      Abstract: Publication date: Available online 31 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Timothy M. Hughes, Suzanne Craft, Laura Baker, Mark A. Espeland, Stephen R. Rapp, Kaycee M. Sink, Alain G. Bertoni, Gregory L. Burke, Rebecca F. Gottesman, Erin D. Michos, José A. Luchsinger, Annette L. Fitzpatrick, Kathleen M. Hayden
      Background We examined whether changes in metabolic factors over 10 years were associated with cognitive performance. Methods Participants from the Multi-Ethnic Study of Atherosclerosis were followed since baseline (2000–2002) with five clinical examinations. At exam 5 (2010–2012), they received a short cognitive battery (Cognitive Abilities Screening Instrument [CASI], Digit Symbol Coding [DSC], and Digit Span [DS]). We examined associations between baseline metabolic factors and their changes over time before cognitive testing. Results Among 4392 participants, baseline metabolic disorders (fasting glucose, systolic and diastolic blood pressures) were significantly associated with poorer CASI, DSC, and DS scores measured 10 years later. Increases in blood pressure were associated with lower cognitive performance. Results did not differ by race/ethnicity and were stronger among those without the APOE ε4 allele. Conclusions Cognitive performance was associated with antecedent abnormalities in glucose metabolism and blood pressure increases. Findings appeared stronger among APOE ε4-negative participants.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.003
       
 
 
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