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Showing 1 - 200 of 3044 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 22, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 21, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 84, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 23, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 28, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 341, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 215, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 23, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
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Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 3)
Acute Pain     Full-text available via subscription   (Followers: 13)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 135, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.739, h-index: 33)
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Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
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Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
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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)
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Advances in Digestive Medicine     Open Access   (Followers: 5)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
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Advances in Ecological Research     Full-text available via subscription   (Followers: 41, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 40, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 48, 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: 11)
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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: 8, SJR: 0.497, h-index: 31)
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: 35, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 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: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
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: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, 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: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 61)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 2, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 349, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 7, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 318, 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: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 8, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 407, 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: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 39, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 54, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 8, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 47, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 48, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 45, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 39, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 16, 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: 24, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 33, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 46, 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: 192, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 56, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 4)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 24, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 26, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 34, 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: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 55, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 9)
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  
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Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 167, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 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  
Animal Behaviour     Hybrid Journal   (Followers: 157, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (Followers: 1, SJR: 0.394, h-index: 30)
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Journal Cover Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
  [5 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2352-8729
   Published by Elsevier Homepage  [3044 journals]
  • Blood-based metabolic signatures in Alzheimer's disease

    • Authors: Francisca A. de Leeuw; Carel F.W. Peeters; Maartje I. Kester; Amy C. Harms; Eduard A. Struys; Thomas Hankemeier; Herman W.T. van Vlijmen; Sven J. van der Lee; Cornelia M. van Duijn; Philip Scheltens; Ays E. Demirkan; Mark A. van de Wiel; Wiesje M. van der Flier; Charlotte E. Teunissen
      Abstract: Publication date: Available online 6 September 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Francisca A. de Leeuw, Carel F.W. Peeters, Maartje I. Kester, Amy C. Harms, Eduard A. Struys, Thomas Hankemeier, Herman W.T. van Vlijmen, Sven J. van der Lee, Cornelia M. van Duijn, Philip Scheltens, Ays E. Demirkan, Mark A. van de Wiel, Wiesje M. van der Flier, Charlotte E. Teunissen
      Introduction Identification of blood-based metabolic changes might provide early and easy-to-obtain biomarkers. Methods We included 127 Alzheimer's disease (AD) patients and 121 control subjects with cerebrospinal fluid biomarker-confirmed diagnosis (cutoff tau/amyloid beta peptide 42 0.52). Mass spectrometry platforms determined the concentrations of 53 amine compounds, 22 organic acid compounds, 120 lipid compounds, and 40 oxidative stress compounds. Multiple signatures were assessed: differential expression (nested linear models), classification (logistic regression), and regulatory (network extraction). Results Twenty-six metabolites were differentially expressed. Metabolites improved the classification performance of clinical variables from 74% to 79%. Network models identified five hubs of metabolic dysregulation: tyrosine, glycylglycine, glutamine, lysophosphatic acid C18:2, and platelet-activating factor C16:0. The metabolite network for apolipoprotein E (APOE) ε4 negative AD patients was less cohesive compared with the network for APOE ε4 positive AD patients. Discussion Multiple signatures point to various promising peripheral markers for further validation. The network differences in AD patients according to APOE genotype may reflect different pathways to AD.

      PubDate: 2017-09-11T11:15:30Z
      DOI: 10.1016/j.dadm.2017.07.006
  • 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

    • 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
  • Plasma Aβ42/40 ratios as biomarkers for Aβ cerebral deposition in
           cognitively normal individuals

    • Authors: Noelia Fandos; Virginia Pérez-Grijalba; Pedro Pesini; Salvador Olmos; Matías Bossa; Victor L. Villemagne; James Doecke; Christopher Fowler; Colin L. Masters; Manuel Sarasa
      Abstract: Publication date: Available online 30 August 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Noelia Fandos, Virginia Pérez-Grijalba, Pedro Pesini, Salvador Olmos, Matías Bossa, Victor L. Villemagne, James Doecke, Christopher Fowler, Colin L. Masters, Manuel Sarasa
      Introduction Plasma amyloid β (Aβ) peptides have been previously studied as candidate biomarkers to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Methods Free and total Aβ42/40 plasma ratios (FP42/40 and TP42/40, respectively) were determined using AB test assays in cognitively normal subjects from the Australian Imaging, Biomarker and Lifestyle Flagship Study. This population was followed-up for 72 months and their cortical Aβ burden was assessed with positron emission tomography. Results Cross-sectional and longitudinal analyses showed an inverse association of Aβ42/40 plasma ratios and cortical Aβ burden. Optimized as a screening tool, TP42/40 reached 81% positive predictive value of high cortical Aβ burden, which represents 110% increase over the population prevalence of cortical Aβ positivity. Discussion These findings support the use of plasma Aβ42/40 ratios as surrogate biomarkers of cortical Aβ deposition and enrichment tools, reducing the number of subjects submitted to invasive tests and, consequently, recruitment costs in clinical trials targeting cognitively normal individuals.

      PubDate: 2017-09-06T09:53:01Z
      DOI: 10.1016/j.dadm.2017.07.004
  • Alzheimer's disease genetic risk variants beyond APOEε4 predict

    • Authors: Jesse Mez; Jessica R. Marden; Shubharbrata Mukherjee; Stefan Walter; Laura E. Gibbons; Alden L. Gross; Laura B. Zahodne; Paola Gilsanz; Paul Brewster; Kwangsik Nho; Paul K. Crane; Eric B. Larson; M. Maria Glymour
      Abstract: Publication date: Available online 14 August 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Jesse Mez, Jessica R. Marden, Shubharbrata Mukherjee, Stefan Walter, Laura E. Gibbons, Alden L. Gross, Laura B. Zahodne, Paola Gilsanz, Paul Brewster, Kwangsik Nho, Paul K. Crane, Eric B. Larson, M. Maria Glymour
      Introduction We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. Methods We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. Results Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00–1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41–1.00, P = .05). Discussion Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.

      PubDate: 2017-08-19T00:48:40Z
      DOI: 10.1016/j.dadm.2017.07.002
  • 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
  • Body mass index in midlife and dementia: Systematic review and
           meta-regression analysis of 589,649 men and women followed in longitudinal

    • Authors: Emiliano Albanese; Lenore J. Launer; Matthias Egger; Martin J. Prince; Panteleimon Giannakopoulos; Frank J. Wolters; Kieren Egan
      Abstract: Publication date: Available online 20 June 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Emiliano Albanese, Lenore J. Launer, Matthias Egger, Martin J. Prince, Panteleimon Giannakopoulos, Frank J. Wolters, Kieren Egan
      Introduction We conducted a meta-analysis of the conflicting epidemiologic evidence on the association between midlife body mass index (BMI) and dementia. Methods We searched standard databases to identify prospective, population-based studies of dementia risk by midlife underweight, overweight, and obesity. We performed random-effects meta-analyses and meta-regressions of adjusted relative risk (RR) estimates and formally explored between-study heterogeneity. Results We included 19 studies on 589,649 participants (2040 incident dementia cases) followed up for up to 42 years. Midlife (age 35 to 65 years) obesity (BMI ≥ 30) (RR, 1.33; 95% confidence interval [CI], 1.08–1.63), but not overweight (25 < BMI < 30) (RR, 1.07; 95% CI, 0.96–1.20), was associated with dementia in late life. The association with midlife underweight (RR, 1.39; 95% CI, 1.13–1.70) was potentially driven by residual confounding (P from meta-regression = .004), selection (P = .046), and information bias (P = .007). Discussion Obesity in midlife increases the risk of dementia. The association between underweight and dementia remains controversial.

      PubDate: 2017-06-24T02:51:04Z
      DOI: 10.1016/j.dadm.2017.05.007
  • Amyloid-β–associated cognitive decline in the absence of clinical
           disease progression and systemic illness

    • Authors: Karra D. Harrington; Yen Ying Lim; David Ames; Jason Hassenstab; Simon M. Laws; Ralph N. Martins; Stephanie Rainey-Smith; Joanne Robertson; Christopher C. Rowe; Olivier Salvado; Vincent Doré; Victor L. Villemagne; Peter J. Snyder; Colin L. Masters; Paul Maruff
      Abstract: Publication date: Available online 9 June 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Karra D. Harrington, Yen Ying Lim, David Ames, Jason Hassenstab, Simon M. Laws, Ralph N. Martins, Stephanie Rainey-Smith, Joanne Robertson, Christopher C. Rowe, Olivier Salvado, Vincent Doré, Victor L. Villemagne, Peter J. Snyder, Colin L. Masters, Paul Maruff
      Introduction High levels of amyloid-β (Aβ) are associated with cognitive decline in cognitively normal (CN) older adults. This study investigated the nature of cognitive decline in healthy individuals who did not progress to mild cognitive impairment or dementia. Method Cognition was measured over 72 months and compared between low (Aβ−) and high (Aβ+) CN older adults (n = 335) who did not progress to mild cognitive impairment or dementia and who remained free of severe or uncontrolled systemic illness. Results Compared to the Aβ− group, the Aβ+ group showed no cognitive impairment at baseline but showed substantial decline in verbal learning, episodic memory, and attention over 72 months. Discussion Moderate cognitive decline, particularly for learning and memory, was associated with Aβ+ in CN older adults in the absence of clinical disease progression and uncontrolled or serious comorbid illness.

      PubDate: 2017-06-14T01:05:02Z
      DOI: 10.1016/j.dadm.2017.05.006
  • Neuroticism, depression, and anxiety traits exacerbate the state of

    • Authors: Valérie Zufferey; Alessia Donati; Julius Popp; Reto Meuli; Jérôme Rossier; Richard Frackowiak; Bogdan Draganski; Armin von Gunten; Ferath Kherif
      Abstract: Publication date: Available online 31 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Valérie Zufferey, Alessia Donati, Julius Popp, Reto Meuli, Jérôme Rossier, Richard Frackowiak, Bogdan Draganski, Armin von Gunten, Ferath Kherif
      Introduction Certain personality traits are associated with higher risk of Alzheimer's disease, similar to cognitive impairment. The identification of biological markers associated with personality in mild cognitive impairment could advance the early detection of Alzheimer's disease. Methods We used hierarchical multivariate linear models to quantify the interaction between personality traits, state of cognitive impairment, and MRI biomarkers (gray matter brain volume, gray matter mean water diffusion) in the medial temporal lobe (MTL). Results Over and above a main effect of cognitive state, the multivariate linear model showed significant interaction between cognitive state and personality traits predicting MTL abnormality. The interaction effect was mainly driven by neuroticism and its facets (anxiety, depression, and stress) and was associated with right-left asymmetry and an anterior to posterior gradient in the MTL. Discussion Our results support the hypothesis that personality traits can alter the vulnerability and pathoplasticity of disease and therefore modulate related biomarker expression.

      PubDate: 2017-06-03T22:51:02Z
      DOI: 10.1016/j.dadm.2017.05.002
  • A classification algorithm for predicting progression from normal
           cognition to mild cognitive impairment across five cohorts: The
           preclinical AD consortium

    • Authors: Alden L. Gross; Jason Hassenstab; Sterling C. Johnson; Lindsay R. Clark; Susan M. Resnick; Melissa Kitner-Triolo; Colin L. Masters; Paul Maruff; John C. Morris; Anja Soldan; Corinne Pettigrew; Marilyn S. Albert
      Abstract: Publication date: Available online 30 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Alden L. Gross, Jason Hassenstab, Sterling C. Johnson, Lindsay R. Clark, Susan M. Resnick, Melissa Kitner-Triolo, Colin L. Masters, Paul Maruff, John C. Morris, Anja Soldan, Corinne Pettigrew, Marilyn S. Albert
      Introduction We established a method for diagnostic harmonization across multiple studies of preclinical Alzheimer's disease and validated the method by examining its relationship with clinical status and cognition. Methods Cognitive and clinical data were used from five studies (N = 1746). Consensus diagnoses established in each study used criteria to identify progressors from normal cognition to mild cognitive impairment. Correspondence was evaluated between these consensus diagnoses and three algorithmic classifications based on (1) objective cognitive impairment in 2+ tests only; (2) a Clinical Dementia Rating (CDR) of ≥0.5 only; and (3) both. Associations between baseline cognitive performance and cognitive change were each tested in relation to progression to algorithm-based classifications. Results In each study, an algorithmic classification based on both cognitive testing cutoff scores and a CDR ≥0.5 provided optimal balance of sensitivity and specificity (areas under the curve: 0.85–0.95). Over an average 6.6 years of follow-up (up to 28 years), N = 186 initially cognitively normal participants aged on average 64 years at baseline progressed (incidence rate: 15.3 people/1000 person-years). Baseline cognitive scores and cognitive change were associated with future diagnostic status using this algorithmic classification. Discussion Both cognitive tests and CDR ratings can be combined across multiple studies to obtain a reliable algorithmic classification with high specificity and sensitivity. This approach may be applicable to large cohort studies and to clinical trials focused on preclinical Alzheimer's disease because it provides an alternative to implementation of a time-consuming adjudication panel.

      PubDate: 2017-06-03T22:51:02Z
      DOI: 10.1016/j.dadm.2017.05.003
  • Phenoconversion from probable rapid eye movement sleep behavior disorder
           to mild cognitive impairment to dementia in a population-based sample

    • Authors: Youngsin Jung; Brendon P. Boot; Michelle M. Mielke; Tanis J. Ferman; Yonas E. Geda; Eric McDade; Teresa J.H. Christianson; David S. Knopman; Erik K. St Louis; Michael H. Silber; Ronald C. Petersen; Bradley F. Boeve
      Abstract: Publication date: Available online 30 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Youngsin Jung, Brendon P. Boot, Michelle M. Mielke, Tanis J. Ferman, Yonas E. Geda, Eric McDade, Teresa J.H. Christianson, David S. Knopman, Erik K. St Louis, Michael H. Silber, Ronald C. Petersen, Bradley F. Boeve
      Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies.

      PubDate: 2017-06-03T22:51:02Z
      DOI: 10.1016/j.dadm.2017.05.004
  • 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
  • Early diagnosis of mild cognitive impairment and Alzheimer's disease based
           on salivary lactoferrin

    • Authors: Eva Carro; Fernando Bartolomé; Félix Bermejo-Pareja; Alberto Villarejo; José Antonio Molina; Pablo Ortiz; Miguel Calero; Alberto Rabano; José Luis Cantero; Gorka Orive
      Abstract: Publication date: Available online 26 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Eva Carro, Fernando Bartolomé, Félix Bermejo-Pareja, Alberto Villarejo, José Antonio Molina, Pablo Ortiz, Miguel Calero, Alberto Rabano, José Luis Cantero, Gorka Orive
      Introduction The Alzheimer's disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity. Methods Here, we show a novel, straight-forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed. Results We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross-sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aβ42. Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD. Conclusion This biomarker may offer new insights in the early diagnostics for AD.

      PubDate: 2017-05-29T20:29:04Z
      DOI: 10.1016/j.dadm.2017.04.002
  • Longitudinal changes in amyloid positron emission tomography and
           volumetric magnetic resonance imaging in the nondemented Down syndrome

    • 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
  • Consensus guidelines for lumbar puncture in patients with neurological

    • Authors: Sebastiaan Engelborghs; Ellis Niemantsverdriet; Hanne Struyfs; Kaj Blennow; Raf Brouns; Manuel Comabella; Irena Dujmovic; Wiesje van der Flier; Lutz Frölich; Daniela Galimberti; Sharmilee Gnanapavan; Bernhard Hemmer; Erik Hoff; Jakub Hort; Ellen Iacobaeus; Martin Ingelsson; Frank Jan de Jong; Michael Jonsson; Michael Khalil; Jens Kuhle; Alberto Lleó; Alexandre de Mendonça; José Luis Molinuevo; Guy Nagels; Claire Paquet; Lucilla Parnetti; Gerwin Roks; Pedro Rosa-Neto; Philip Scheltens; Constance Skårsgard; Erik Stomrud; Hayrettin Tumani; Pieter Jelle Visser; Anders Wallin; Bengt Winblad; Henrik Zetterberg; Flora Duits; Charlotte E. Teunissen
      Abstract: Publication date: Available online 18 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Sebastiaan Engelborghs, Ellis Niemantsverdriet, Hanne Struyfs, Kaj Blennow, Raf Brouns, Manuel Comabella, Irena Dujmovic, Wiesje van der Flier, Lutz Frölich, Daniela Galimberti, Sharmilee Gnanapavan, Bernhard Hemmer, Erik Hoff, Jakub Hort, Ellen Iacobaeus, Martin Ingelsson, Frank Jan de Jong, Michael Jonsson, Michael Khalil, Jens Kuhle, Alberto Lleó, Alexandre de Mendonça, José Luis Molinuevo, Guy Nagels, Claire Paquet, Lucilla Parnetti, Gerwin Roks, Pedro Rosa-Neto, Philip Scheltens, Constance Skårsgard, Erik Stomrud, Hayrettin Tumani, Pieter Jelle Visser, Anders Wallin, Bengt Winblad, Henrik Zetterberg, Flora Duits, Charlotte E. Teunissen
      Introduction Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. Methods We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and BioMS consortia (evidence level III). Results Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. Discussion When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate.

      PubDate: 2017-05-19T16:01:06Z
      DOI: 10.1016/j.dadm.2017.04.007
  • Lumbar puncture in patients with neurologic conditions

    • Authors: Rosha B. Mofrad; Femke H. Bouwman; Rosalinde E.R. Slot; Tessa Timmers; Wiesje M. van der Flier; Philip Scheltens; Charlotte E. Teunissen
      Abstract: Publication date: Available online 18 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Rosha B. Mofrad, Femke H. Bouwman, Rosalinde E.R. Slot, Tessa Timmers, Wiesje M. van der Flier, Philip Scheltens, Charlotte E. Teunissen
      A lumbar puncture is performed to obtain cerebral spinal fluid. It is implemented in the clinic on a routine basis to aid the diagnosis of neurologic diseases, such as dementia. This video will show the lumbar puncture procedure as routinely performed in the VUmc Alzheimer Center.

      PubDate: 2017-05-19T16:01:06Z
      DOI: 10.1016/j.dadm.2017.04.008
  • Longitudinal evaluation of criteria for subjective cognitive decline and
           preclinical Alzheimer's disease in a memory clinic sample

    • Authors: Marie Eckerström; Mattias Göthlin; Sindre Rolstad; Erik Hessen; Carl Eckerström; Arto Nordlund; Boo Johansson; Johan Svensson; Michael Jonsson; Simona Sacuiu; Anders Wallin
      Abstract: Publication date: Available online 16 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Marie Eckerström, Mattias Göthlin, Sindre Rolstad, Erik Hessen, Carl Eckerström, Arto Nordlund, Boo Johansson, Johan Svensson, Michael Jonsson, Simona Sacuiu, Anders Wallin
      Introduction Subjective cognitive decline (SCD) and biomarker-based “at-risk” concepts such as “preclinical” Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications. Methods Memory clinic patients (n = 235) were classified as SCD (n = 122): subtle cognitive decline (n = 36) and mild cognitive impairment (n = 77) and subsequently subclassified into SCDplus and National Institute on Aging–Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications. Results Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage 2. Discussion In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.

      PubDate: 2017-05-19T16:01:06Z
      DOI: 10.1016/j.dadm.2017.04.006
  • Nutrients required for phospholipid synthesis are lower in blood and
           cerebrospinal fluid in mild cognitive impairment and Alzheimer's disease

    • Authors: Nick van Wijk; Rosalinde E.R. Slot; Flora H. Duits; Marieke Strik; Egbert Biesheuvel; John W.C. Sijben; Marinus A. Blankenstein; Jörgen Bierau; Wiesje M. van der Flier; Philip Scheltens; Charlotte E. Teunissen
      Abstract: Publication date: Available online 16 May 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Nick van Wijk, Rosalinde E.R. Slot, Flora H. Duits, Marieke Strik, Egbert Biesheuvel, John W.C. Sijben, Marinus A. Blankenstein, Jörgen Bierau, Wiesje M. van der Flier, Philip Scheltens, Charlotte E. Teunissen
      Introduction Synaptic membrane formation depends on nutrients that fuel metabolic pathways for the synthesis of constituent phospholipids. Consequently, insufficient availability of such nutrients may restrict membrane formation and contribute to synaptic dysfunction in Alzheimer's disease (AD). We assessed whether blood and cerebrospinal fluid (CSF) concentrations of nutrients related to phospholipid synthesis differ among patients with AD, mild cognitive impairment (MCI), and control subjects. Methods Concentrations of uridine, choline, folate, homocysteine, and other related metabolites were analyzed in paired blood and CSF samples from subjects selected from the Amsterdam Dementia Cohort with AD (n = 150; age, 66 ± 7 years; 37% female), MCI (n = 148; age, 66 ± 8 years; 37% female), and control subjects (n = 148; age, 59 ± 8 years; 38% female). Results Age- and gender-adjusted analysis of variance revealed different concentrations of circulating uridine, choline, and folate and CSF uridine, folate, and homocysteine (all P < .05) among the three diagnostic groups. Post hoc pairwise comparison showed that subjects with AD had lower CSF uridine, plasma choline and higher CSF homocysteine concentrations, whereas subjects with MCI had lower plasma and CSF uridine, serum and CSF folate, and higher CSF homocysteine concentrations compared with control subjects (all P < .05), with differences ranging from −11 to +22%. Discussion AD and MCI patients have lower levels of nutrients involved in phospholipid synthesis. The current observations warrant exploration of the application of nutritional strategies in the early stages of AD.

      PubDate: 2017-05-19T16:01:06Z
      DOI: 10.1016/j.dadm.2017.04.005
  • Altered levels of blood proteins in Alzheimer's disease longitudinal
           study: Results from Australian Imaging Biomarkers Lifestyle Study of
           Ageing cohort

    • Authors: V.B. Gupta; E. Hone; S. Pedrini; James Doecke; Sid O'Bryant; Ian James; Ashley I. Bush; Christopher C. Rowe; Victor L. Villemagne; David Ames; Colin L. Masters; R.N. Martins
      Abstract: Publication date: Available online 23 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): V.B. Gupta, E. Hone, S. Pedrini, James Doecke, Sid O'Bryant, Ian James, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, R.N. Martins
      A blood-based biomarker panel to identify individuals with preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first step for routine testing. We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort. Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P = .0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P = .0008). These data suggest that apoJ may have potential in the context of use (COU) of AD diagnostics, I-309 may be specifically useful in the COU of identifying individuals at greatest risk for progressing toward AD. This work takes an initial step toward identifying blood biomarkers with potential use in the diagnosis and prognosis of AD and should be validated across other prospective cohorts.

      PubDate: 2017-04-28T12:24:51Z
      DOI: 10.1016/j.dadm.2017.04.003
  • Single-nucleotide polymorphisms are associated with cognitive decline at
           Alzheimer's disease conversion within mild cognitive impairment patients

    • Authors: Eunjee Lee; Kelly S. Giovanello; Andrew J. Saykin; Fengchang Xie; Dehan Kong; Yue Wang; Liuqing Yang; Joseph G. Ibrahim; P. Murali Doraiswamy; Hongtu Zhu
      Abstract: Publication date: Available online 23 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Eunjee Lee, Kelly S. Giovanello, Andrew J. Saykin, Fengchang Xie, Dehan Kong, Yue Wang, Liuqing Yang, Joseph G. Ibrahim, P. Murali Doraiswamy, Hongtu Zhu
      Introduction The growing public threat of Alzheimer's disease (AD) has raised the urgency to quantify the degree of cognitive decline during the conversion process of mild cognitive impairment (MCI) to AD and its underlying genetic pathway. The aim of this article was to test genetic common variants associated with accelerated cognitive decline after the conversion of MCI to AD. Methods In 583 subjects with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI; ADNI-1, ADNI-Go, and ADNI-2), 245 MCI participants converted to AD at follow-up. We tested the interaction effects between individual single-nucleotide polymorphisms and AD diagnosis trajectory on the longitudinal Alzheimer's Disease Assessment Scale-Cognition scores. Results Our findings reveal six genes, including BDH1, ST6GAL1, RAB20, PDS5B, ADARB2, and SPSB1, which are directly or indirectly related to MCI conversion to AD. Discussion This genome-wide association study sheds light on a genetic mechanism of longitudinal cognitive changes during the transition period from MCI to AD.

      PubDate: 2017-04-28T12:24:51Z
      DOI: 10.1016/j.dadm.2017.04.004
  • Resting-state network dysfunction in Alzheimer's disease: A systematic
           review and meta-analysis

    • Authors: AmanPreet Badhwar; Angela Tam Christian Dansereau Pierre Orban Felix Hoffstaedter
      Abstract: Publication date: Available online 18 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): AmanPreet Badhwar, Angela Tam, Christian Dansereau, Pierre Orban, Felix Hoffstaedter, Pierre Bellec
      Introduction We performed a systematic review and meta-analysis of the Alzheimer's disease (AD) literature to examine consistency of functional connectivity alterations in AD dementia and mild cognitive impairment, using resting-state functional magnetic resonance imaging. Methods Studies were screened using a standardized procedure. Multiresolution statistics were performed to assess the spatial consistency of findings across studies. Results Thirty-four studies were included (1363 participants, average 40 per study). Consistent alterations in connectivity were found in the default mode, salience, and limbic networks in patients with AD dementia, mild cognitive impairment, or in both groups. We also identified a strong tendency in the literature toward specific examination of the default mode network. Discussion Convergent evidence across the literature supports the use of resting-state connectivity as a biomarker of AD. The locations of consistent alterations suggest that highly connected hub regions in the brain might be an early target of AD.

      PubDate: 2017-04-20T17:48:08Z
  • Multidimensional assessment of challenging behaviors in advanced stages of
           dementia in nursing homes—The insideDEM framework

    • Authors: Stefan Teipel; Christina Heine; Albert Hein; Frank Krüger; Andreas Kutschke; Sven Kernebeck; Margareta Halek; Sebastian Bader; Thomas Kirste
      Abstract: Publication date: Available online 4 April 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Stefan Teipel, Christina Heine, Albert Hein, Frank Krüger, Andreas Kutschke, Sven Kernebeck, Margareta Halek, Sebastian Bader, Thomas Kirste
      Introduction Assessment of challenging behaviors in dementia is important for intervention selection. Here, we describe the technical and experimental setup and the feasibility of long-term multidimensional behavior assessment of people with dementia living in nursing homes. Methods We conducted 4 weeks of multimodal sensor assessment together with real-time observation of 17 residents with moderate to very severe dementia in two nursing care units. Nursing staff received extensive training on device handling and measurement procedures. Behavior of a subsample of eight participants was further recorded by videotaping for more than 4 weeks during day hours. Sensors were mounted on the participants' wrist and ankle and measured motion, rotation, as well as surrounding loudness level, light level, and air pressure. Results Participants were in moderate to severe stages of dementia. Almost 100% of participants exhibited relevant levels of challenging behaviors. Automated quality control detected 155 potential issues. But only 11% of the recordings have been influenced by noncompliance of the participants. Qualitative debriefing of staff members suggested that implementation of the technology and observation platform in the routine procedures of the nursing home units was feasible and identified a range of user- and hardware-related implementation and handling challenges. Discussion Our results indicate that high-quality behavior data from real-world environments can be made available for the development of intelligent assistive systems and that the problem of noncompliance seems to be manageable. Currently, we train machine-learning algorithms to detect episodes of challenging behaviors in the recorded sensor data.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.006
  • Detecting functional decline from normal aging to dementia: Development
           and validation of a short version of the Amsterdam IADL Questionnaire

    • Authors: Roos J. Jutten; Carel F.W. Peeters; Sophie M.J. Leijdesdorff; Pieter J. Visser; Andrea B. Maier; Caroline B. Terwee; Philip Scheltens; Sietske A.M. Sikkes
      Abstract: Publication date: Available online 31 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Roos J. Jutten, Carel F.W. Peeters, Sophie M.J. Leijdesdorff, Pieter J. Visser, Andrea B. Maier, Caroline B. Terwee, Philip Scheltens, Sietske A.M. Sikkes
      Introduction Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A-IADL-Q) was developed: a 70-item proxy-based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality. Methods Study partners of subjects (n = 1355), ranging from cognitively normal to dementia subjects, completed the original A-IADL-Q. We selected the short version items using a stepwise procedure combining missing data, Item Response Theory, and input from respondents and experts. We investigated internal consistency of the short version and concordance with the original version. To assess its construct validity, we additionally investigated concordance between the short version and the Mini–Mental State Examination and Disability Assessment for Dementia. Finally, we investigated differences in instrumental activities of daily living (IADL) scores between diagnostic groups across the dementia spectrum. Results We selected 30 items covering the entire spectrum of IADL functioning. Internal consistency (0.98) and concordance with the original version (0.97) were very high. Concordance with the Mini–Mental State Examination (0.72) and Disability Assessment for Dementia (0.87) scores was high. IADL impairment scores increased across the spectrum from normal cognition to dementia. Discussion The A-IADL-Q short version consists of 30 items. The A-IADL-Q short version has maintained the psychometric quality of the original A-IADL-Q. As such, it is a concise measure of functional decline.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.002
  • Changes in metabolic risk factors over 10 years and their associations
           with late-life cognitive performance: The Multi-Ethnic Study of

    • 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
  • Choroidal thinning: Alzheimer's disease and aging

    • Authors: João Paulo Cunha; Rita Proença; Arnaldo Dias-Santos; Diana Melancia; Rita Almeida; Helena Águas; Bruno Oliveira Santos; Marta Alves; Joana Ferreira; Ana Luísa Papoila; Carlota Louro; António Castanheira-Dinis
      Abstract: Publication date: Available online 30 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): João Paulo Cunha, Rita Proença, Arnaldo Dias-Santos, Diana Melancia, Rita Almeida, Helena Águas, Bruno Oliveira Santos, Marta Alves, Joana Ferreira, Ana Luísa Papoila, Carlota Louro, António Castanheira-Dinis
      Purpose To measure and to compare macular choroidal thickness (CT) between patients with mild Alzheimer's disease (AD), patients without AD, and elderly patients. Methods CT was measured manually in 13 locations at 500-μm intervals of a horizontal and a vertical section from the fovea. Linear regression models were used to analyze the data. Results Fifty patients with a diagnosis of mild AD (73.1 years), 152 patients without AD (71.03 years), and 50 elderly without AD (82.14 years) were included. In the AD patients, CT was significantly thinner in all 13 locations (P < .001—comparing with age-match group), and comparing with the elderly group, a more pronounced difference was found in two locations temporal to the fovea. Conclusions Patients with AD showed a significant choroidal thinning even when compared with elderly subjects. The reduction of CT may aid in the diagnoses of AD, probably reflecting the importance of vascular factors in their pathogenesis.

      PubDate: 2017-04-07T09:51:56Z
      DOI: 10.1016/j.dadm.2017.03.004
  • Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome

    • Authors: Alain D. Dekker; Juan Fortea; Rafael Blesa; Peter P. De Deyn
      Abstract: Publication date: Available online 20 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Alain D. Dekker, Juan Fortea, Rafael Blesa, Peter P. De Deyn
      Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer's disease (AD). Amyloid-β and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Although blood biomarkers have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid-β42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the general population and are increasingly used in clinical practice. Surprisingly, CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF analyses would finally allow for the elucidation of its utility in (differential) diagnoses and staging of disease severity. A sensitive and specific biomarker profile for AD in DS would be of paramount importance to daily care, adaptive caregiving, and specific therapeutic interventions.

      PubDate: 2017-03-24T11:30:56Z
      DOI: 10.1016/j.dadm.2017.02.006
  • CSF biomarker examination as a tool to discriminate behavioral variant
           frontotemporal dementia from primary psychiatric disorders

    • Authors: Everard G.B. Vijverberg; Annemiek Dols; Welmoed A. Krudop; Marta Del Campo Milan; Cora J. Kerssens; Flora Gossink; Niels D. Prins; Max L. Stek; Philip Scheltens; Charlotte E. Teunissen; Yolande A.L. Pijnenburg
      Abstract: Publication date: Available online 2 March 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Everard G.B. Vijverberg, Annemiek Dols, Welmoed A. Krudop, Marta Del Campo Milan, Cora J. Kerssens, Flora Gossink, Niels D. Prins, Max L. Stek, Philip Scheltens, Charlotte E. Teunissen, Yolande A.L. Pijnenburg
      Introduction To prospectively determine the diagnostic value of cerebrospinal fluid (CSF) levels total-tau (tau) to amyloid-β1–42 ratio (Aβ1–42) ratio (tau/Aβ1–42 ratio), phosphorylated-tau (p-tau) to tau ratio (p-tau/tau ratio), neurofilament light chain (NfL) and YKL40 in the late-onset frontal lobe syndrome, in particular for the differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) versus primary psychiatric disorders (PSY). Method We included patients with a multidisciplinary 2-year-follow-up diagnosis of probable/definite bvFTD (n = 22) or PSY (n = 25), who underwent a detailed neuropsychiatric clinical examination, neuropsychological test battery, and magnetic resonance imaging at baseline. In all cases, CSF was collected through lumbar puncture at baseline. We compared CSF biomarker levels between the two groups and measured the diagnostic accuracy for probable/definite bvFTD, using the follow-up diagnosis as the reference standard. Results The best discriminators between probable/definite bvFTD and PSY were the levels of CSF NfL (area under the curve [AUC] 0.93, P < .001, 95% confidence interval [CI] 0.85–1.00), p-tau/tau ratio (AUC 0.87, P < .001, 95% CI 0.77–0.97), and YKL40 (AUC 0.82, P = .001, 95% CI 0.68–0.97). The combination of these three biomarkers had a sensitivity of 91% (95% CI 66%–100%) at a specificity of 83% (95% CI 65%–95%) with an AUC of 0.94 (P < .001, 95% CI 0.87–1.00) for bvFTD. CSF tau/Aβ1–42 ratio was less accurate in differentiating between bvFTD and PSY. Discussion We found a good diagnostic accuracy for higher levels of CSF NfL and YKL40 and reduced p-tau/tau ratio in distinguishing bvFTD from PSY. We advocate the use of these CSF biomarkers as potential additional tools to neuroimaging in the diagnosis of bvFTD versus PSY.

      PubDate: 2017-03-05T20:50:37Z
      DOI: 10.1016/j.dadm.2017.01.009
  • Development of an instrument to assess social functioning in dementia: The
           Social Functioning in Dementia scale

    • Authors: Andrew Sommerlad; David Singleton; Rebecca Jones; Sube Banerjee; Gill Livingston
      Abstract: Publication date: Available online 24 February 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Andrew Sommerlad, David Singleton, Rebecca Jones, Sube Banerjee, Gill Livingston
      Background Social functioning is a core domain in the life of people with dementia, but there is no accepted instrument to measure it. Aims To develop the Social Functioning in Dementia (SF-DEM) scale and test its psychometric properties for assessing social function in people with dementia. Method We interviewed people with mild dementia and family caregivers to develop patient and caregiver-rated SF-DEM versions and then refined them through interviews with health care professionals. We tested its psychometric properties in 30 dyads of people with dementia and family caregivers. Results Both SF-DEM versions had content validity and demonstrated concurrent validity against a single item rating overall social functioning (patient rated r = 0.42, 95% CI [0.07–0.68]; caregiver rated r = 0.59, 95% CI [0.29–0.78]). All participants found it acceptable. Analyses showed reliability (test–retest, interrater, internal consistency) and indications of responsiveness to change. Conclusions SF-DEM shows promise as a valid, reliable, acceptable measure of social functioning in dementia.

      PubDate: 2017-02-25T16:12:06Z
      DOI: 10.1016/j.dadm.2017.02.001
  • Pathophysiologic relationship between Alzheimer's disease, cerebrovascular
           disease, and cardiovascular risk: A review and synthesis

    • Authors: Cláudia Y. Santos; Peter J. Snyder; Wen-Chih Wu; Mia Zhang; Ana Echeverria; Jessica Alber
      Abstract: Publication date: Available online 9 February 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Cláudia Y. Santos, Peter J. Snyder, Wen-Chih Wu, Mia Zhang, Ana Echeverria, Jessica Alber
      As the population ages due to demographic trends and gains in life expectancy, the incidence and prevalence of dementia increases, and the need to understand the etiology and pathogenesis of dementia becomes ever more urgent. Alzheimer's disease (AD), the most common form of dementia, is a complex disease, the mechanisms of which are poorly understood. The more we learn about AD, the more questions are raised about our current conceptual models of disease. In the absence of a cure or the means by which to slow disease progress, it may be prudent to apply our current knowledge of the intersection between AD, cardiovascular disease, and cerebrovascular disease to foster efforts to delay or slow the onset of AD. This review discusses our current understanding of the epidemiology, genetics, and pathophysiology of AD, the intersection between AD and vascular causes of dementia, and proposes future directions for research and prevention.

      PubDate: 2017-02-13T11:18:18Z
      DOI: 10.1016/j.dadm.2017.01.005
  • A robust biomarker of large-scale network failure in Alzheimer's disease

    • Authors: Daniela Wiepert; Val J. Lowe; David Knopman; Bradley Boeve; Jonathan Graff-Radford; Ronald Peterson; Clifford Jack; David Jones
      Abstract: Publication date: Available online 25 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Daniela Wiepert, Val J. Lowe, David Knopman, Bradley Boeve, Jonathan Graff-Radford, Ronald Peterson, Clifford Jack, David Jones
      Introduction Biomarkers for Alzheimer's disease (AD) pathophysiology have been developed that focus on various levels of brain organization. However, no robust biomarker of large-scale network failure has been developed. Using the recently introduced cascading network failure model of AD, we developed the network failure quotient (NFQ) as a biomarker of this process. Methods We developed and optimized the NFQ using our recently published analyses of task-free functional magnetic resonance imaging data in clinically normal (n = 43) and AD dementia participants (n = 28) from the Alzheimer's Disease Neuroimaging Initiative. The optimized NFQ (oNFQ) was then validated in a cohort spanning the AD spectrum from the Mayo Clinic (n = 218). Results The oNFQ (d = 1.25, 95% confidence interval [1.25, 1.26]) had the highest effect size for differentiating persons with AD dementia from clinically normal participants. The oNFQ measure performed similarly well on the validation Mayo Clinic sample (d = 1.44, 95% confidence interval [1.43, 1.44]). The oNFQ was also associated with other available key biomarkers in the Mayo cohort. Discussion This study demonstrates a measure of functional connectivity, based on a cascading network failure model of AD, and was highly successful in identifying AD dementia. A robust biomarker of the large-scale effects of AD pathophysiology will allow for richer descriptions of the disease process and its modifiers, but is not currently suitable for discriminating clinical diagnostic categories. The large-scale network level may be one of the earliest manifestations of AD, making this an attractive target for continued biomarker development to be used in prevention trials.

      PubDate: 2017-02-01T09:24:40Z
      DOI: 10.1016/j.dadm.2017.01.004
  • Serum IL-8 is a marker of white-matter hyperintensities in patients with
           Alzheimer disease

    • Authors: Yanan Zhu; Yuek Ling Chai; Saima Hilal; M. Kamran Ikram; Narayanaswamy Venketasubramanian; Boon-Seng Wong; Christopher P. Chen; Mitchell K.P. Lai
      Abstract: Publication date: Available online 23 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Yanan Zhu, Yuek Ling Chai, Saima Hilal, M. Kamran Ikram, Narayanaswamy Venketasubramanian, Boon-Seng Wong, Christopher P. Chen, Mitchell K.P. Lai
      Introduction Neuroinflammation and cerebrovascular disease (CeVD) have been implicated in cognitive impairment and Alzheimer disease (AD). The present study aimed to examine serum inflammatory markers in preclinical stages of dementia and in AD, as well as to investigate their associations with concomitant CeVD. Methods We performed a cross-sectional case–control study including 96 AD, 140 cognitively impaired no dementia (CIND), and 79 noncognitively impaired participants. All subjects underwent neuropsychological and neuroimaging assessments, as well as collection of blood samples for measurements of serum samples interleukin (IL)-6, IL-8, and tumor necrosis factor α levels. Subjects were classified as CIND or dementia based on clinical criteria. Significant CeVD, including white-matter hyperintensities (WMHs), lacunes, and cortical infarcts, was assessed by magnetic resonance imaging. Results After controlling for covariates, higher concentrations of IL-8, but not the other measured cytokines, were associated with both CIND and AD only in the presence of significant CeVD (CIND with CeVD: odds ratios [ORs] 4.53; 95% confidence interval [CI] 1.5–13.4 and AD with CeVD: OR 7.26; 95% CI 1.2–43.3). Subsequent multivariate analyses showed that among the types of CeVD assessed, only WMH was associated with higher IL-8 levels in CIND and AD (WMH: OR 2.81; 95% CI 1.4–5.6). Discussion Serum IL-8 may have clinical utility as a biomarker for WMH in AD. Longitudinal follow-up studies would help validate these findings.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2017.01.001
  • Macrovascular and microvascular cerebral blood flow in adults at risk for
           Alzheimer's disease

    • Authors: Lindsay R. Clark; Sara E. Berman; Leonardo A. Rivera-Rivera; Siobhan M. Hoscheidt; Burcu F. Darst; Corinne D. Engelman; Howard A. Rowley; Cynthia M. Carlsson; Sanjay Asthana; Patrick Turski; Oliver Wieben; Sterling C. Johnson
      Abstract: Publication date: Available online 23 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Lindsay R. Clark, Sara E. Berman, Leonardo A. Rivera-Rivera, Siobhan M. Hoscheidt, Burcu F. Darst, Corinne D. Engelman, Howard A. Rowley, Cynthia M. Carlsson, Sanjay Asthana, Patrick Turski, Oliver Wieben, Sterling C. Johnson
      Introduction Capillary hypoperfusion is reported in asymptomatic adults at risk for Alzheimer's disease (AD), but the extent that can be explained by reduced flow in intracranial arteries is unknown. We investigated cerebral microvascular and macrovascular blood flow and potential moderators of this relationship. Methods One hundred fifty-five asymptomatic adults enriched for AD risk (mean age 61 years, 71% parental history of AD) underwent magnetic resonance imaging that included pseudocontinuous arterial spin labeling and phase-contrast vastly undersampled isotropic projection 4D-flow imaging. Voxel-wise regression models investigated the relationship between mean flow in bilateral cerebral arteries and whole-brain cerebral perfusion, and subsequent models tested if age, cardiovascular, and genetic factors moderated this relationship. Results Mean arterial blood flow through middle cerebral arteries (MCAs) and internal carotid arteries was positively associated with perfusion in large cortical clusters (P < .05, false discovery rate corrected). Trends were observed for the interactions MCA flow × age and MCA flow × cardiovascular risk on cerebral perfusion (P < .001, uncorrected). Discussion These findings provide evidence that capillary perfusion measured via pseudocontinuous arterial spin labeling is strongly dependent on inflow from larger cerebral arteries. Further studies are warranted to investigate possible alterations between macrovascular and microvascular flow in advanced age and elevated cardiovascular risk in asymptomatic adults at risk for AD.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2017.01.002
  • Sleep-wake cycle disturbances in elderly acute general medical inpatients:
           Longitudinal relationship to delirium and dementia

    • Authors: James M. FitzGerald; Niamh O'Regan; Dimitrios Adamis; Suzanne Timmons; Colum P. Dunne; Paula T. Trzepacz; David J. Meagher
      Abstract: Publication date: Available online 21 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): James M. FitzGerald, Niamh O'Regan, Dimitrios Adamis, Suzanne Timmons, Colum P. Dunne, Paula T. Trzepacz, David J. Meagher
      Introduction Sleep disturbances in elderly medical inpatients are common, but their relationship to delirium and dementia has not been studied. Methods Sleep and delirium status were assessed daily for a week in 145 consecutive newly admitted elderly acute general hospital patients using the Delirium Rating Scale-Revised-98 (DRS-R98), Diagnostic and Statistical Manual 5, and Richards-Campbell Sleep Quality Scale measures. The longitudinal relationship between DRS-R98 and Richards-Campbell Sleep Quality Scale sleep scores and delirium, also with dementia as a covariate, was evaluated using generalized estimating equation logistic regression. Results The cohort was divided into delirium only, dementia only, comorbid delirium-dementia, and no-delirium/no-dementia subgroups. Mean age of total group was 80 ± 6.3, 48% were female, and 31 (21%) had dementia, 29 had delirium at admission (20%), and 27 (18.5%) experienced incident delirium. Mild sleep disturbance (DRS-R98 sleep item score ≥1) occurred for at least 1 day in all groups, whereas moderate sleep disturbance (score ≥2) occurred in significantly more of the prevalent delirium-only (81%; n = 17) cases than incident delirium-only (46%; n = 13) cases (P < .001). There were more cases with DRS-R98 sleep item scores ≥2 (P < .001) in the delirium-only group compared with the other subgroups. Severity of sleep-wake cycle disturbance over time was significantly associated with Diagnostic and Statistical Manual 5 delirium status but not with age, sex, or dementia (P < .001). Conclusions Observer-rated more severe sleep-wake cycle disturbances are highly associated with delirium irrespective of dementia status, consistent with being a core feature of delirium. Monitoring for altered sleep-wake cycle patterns may be a simple way to improve delirium detection.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2016.12.013
  • Peripheral inflammatory markers indicate microstructural damage within the
           periventricular white matter hyperintensities seen frequently
           in Alzheimer's disease: A preliminary report

    • Authors: Walter Swardfager; Di Yu; Joel E. Ramirez; Hugo Cogo-Moreira; Gregory Szilagyi; Melissa F. Holmes; Christopher J. Scott; Gustavo Scola; Pak C. Chan; Jialun Chen; Parco Chan; Demetrios J. Sahlas; Nathan Herrmann; Krista L. Lanctôt; Ana C. Andreazza; Jacqueline A. Pettersen; Sandra E. Black
      Abstract: Publication date: Available online 21 January 2017
      Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
      Author(s): Walter Swardfager, Di Yu, Joel E. Ramirez, Hugo Cogo-Moreira, Gregory Szilagyi, Melissa F. Holmes, Christopher J. Scott, Gustavo Scola, Pak C. Chan, Jialun Chen, Parco Chan, Demetrios J. Sahlas, Nathan Herrmann, Krista L. Lanctôt, Ana C. Andreazza, Jacqueline A. Pettersen, Sandra E. Black
      Introduction White matter hyperintensities (WMHs) presumed to reflect cerebral small vessel disease and increased peripheral inflammatory markers are found commonly in Alzheimer's disease (AD), but their interrelationships remain unclear. Methods Inflammatory markers were assayed in 54 elderly participants with AD (n = 16). Periventricular WMHs were delineated from T1, T2/proton density, and fluid-attenuated magnetic resonance imaging using semiautomated fuzzy lesion extraction and coregistered with maps of fractional anisotropy (FA), a measure of microstructural integrity assessed using diffusion tensor imaging. Results Mean FA within periventricular WMHs was associated with an inflammatory factor consisting of interleukin (IL)-1β, tumor necrosis factor, IL-10, IL-21, and IL-23 in patients with AD (ρ = −0.703, P = .002) but not in healthy elderly (ρ = 0.217, P = .190). Inflammation was associated with greater FA in deep WMH in healthy elderly (ρ = 0.425, P = .008) but not in patients with AD (ρ = 0.174, P = .520). Discussion Peripheral inflammatory markers may be differentially related to microstructural characteristics within the white matter affected by cerebral small vessel disease in elders with and without AD.

      PubDate: 2017-01-25T06:52:50Z
      DOI: 10.1016/j.dadm.2016.12.011
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