Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia
Year: 2017
Type: article
Study design: Observational Study
Abstract: Importance: Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective: To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia. Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype. Results: Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years. Conclusions and Relevance: Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
Source: JAMA Psychiatry
Authors: Willemijn J. Jansen, Rik Ossenkoppele, Betty M. Tijms, Anne M. Fagan, Oskar Hansson, William E. Klunk, Wiesje M. van der Flier, Victor L. Villemagne, Giovanni B. Frisoni, Adam S. Fleisher, Alberto Lleó, Mark A. Mintun, Anders Wallin, Sebastiaan Engelborghs, Duk L. Na, Gäel Chételat, José Luis Molinuevo, Susan M. Landau, Niklas Mattsson, Johannes Kornhuber, Osama Sabri, Christopher C. Rowe, Lucilla Parnetti, Julius Popp, Tormod Fladby, William J. Jagust, Pauline Aalten, Dong Young Lee, Rik Vandenberghe, Catarina Resende de Oliveira, Elisabeth Kapaki, Lutz Froelich, Adrian Ivanoiu, Tomasz Gabryelewicz, Marcel M. Verbeek, Páscual Sanchez-Juan, Helmut Hildebrandt, Vincent Camus, Marzena Zboch, David J. Brooks, Alexander Drzezga, Juha O. Rinne, Andrew Newberg, Alexandre de Mendonça, Marie Sarazin, Gil D. Rabinovici, Karine Madsen, Milica G. Kramberger, Agneta Nordberg, Vincent Mok, Barbara Mroczko, David A. Wolk, Philipp T. Meyer, Magda Tsolaki, Philip Scheltens, Frans R. J. Verhey, Pieter Jelle Visser, Amyloid Biomarker Study Group, Dag Aarsland, Daniel Alcolea, Myriam Alexander, Ina S. Almdahl, Steven E. Arnold, Inês Baldeiras, Henryk Barthel, Bart N.M. van Berckel, Kaj Blennow, Mark A. van Buchem, Enrica Cavedo, Kewei Chen, Elena Chipi, Ann D. Cohen, Stefan Förster, Juan Fortea, Kristian S. Frederiksen, Yvonne Freund-Levi, Olymbia Gkatzima, Mark Forrest Gordon, Timo Grimmer, Harald Hampel, Lucrezia Hausner, Sabine Hellwig, Sanna-Kaisa Herukka, Peter Johannsen, Aleksandra Klimkowicz-Mrowiec, Sebastian Köhler, Norman Koglin, Koen van Laere, Mony de Leon, Viviana Lisetti, Wolfgang Maier, Jan Marcusson, Olga Meulenbroek, Hanne M. Møllergård, John C. Morris, Arto Nordlund, Gerald P. Novak, George P. Paraskevas, Gayan Perera, Oliver Peters, Inez H. G. B. Ramakers, Lorena Rami, Eloy Rodríguez-Rodríguez, Catherine M. Roe, Uros Rot, Eckart Rüther, Isabel Santana, Johannes Schröder, Sang W. Seo, Hilkka Soininen, Luiza Spiru, Erik Stomrud, Hanne Struyfs, Charlotte E. Teunissen, Stephanie J. B. Vos, Linda J. C. van Waalwijk van Doorn, Gunhild Waldemar, Åsa K. Wallin, Jens Wiltfang, Henrik Zetterberg
Institutions: Maastricht University, University of California, San Francisco, Amsterdam Neuroscience, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of California, Berkeley, Washington University in St. Louis, Lund University, University of Pittsburgh, Austin Hospital, Austin Health, University of Geneva, University Hospital of Geneva, Centro San Giovanni di Dio Fatebenefratelli, Eli Lilly (United States), University of California San Diego, Banner Alzheimer’s Institute, Hospital de Sant Pau, Avid Radiopharmaceuticals (United States), University of Gothenburg, University of Antwerp, Samsung Medical Center, Sungkyunkwan University, Inserm, Centre Hospitalier Universitaire de Caen Normandie, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Friedrich-Alexander-Universität Erlangen-Nürnberg, Leipzig University, University of Perugia, Centre Hospitalier Universitaire Vaudois, Akershus University Hospital, Seoul National University, KU Leuven, Centro de Neurociências e Biologia Celular, National and Kapodistrian University of Athens, Eginition Hospital, Heidelberg University, Central Institute of Mental Health, Medizinische Fakultät Mannheim, Cliniques Universitaires Saint-Luc, UCLouvain, Mossakowski Medical Research Institute, Polish Academy of Sciences, Polish Academy of Sciences, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Université de Tours, Centre Hospitalier Universitaire de Tours, Clinical Investigation Center Plurithematic Tours, Wroclaw Medical University, Imperial College London, Medical Research Council, University of Cologne, University of Turku, Turku University Hospital, Turku PET Centre, Thomas Jefferson University, Thomas Jefferson University Hospital, University of Lisbon, Centre Hospitalier Sainte-Anne, Université Paris Descartes, Copenhagen University Hospital, Ljubljana University Medical Centre, Karolinska University Hospital, Karolinska Institutet, Lui Che Woo Institute of Innovative Medicine, Medical University of Białystok, University of Pennsylvania, University Medical Center Freiburg, Aristotle University of Thessaloniki, Stavanger University Hospital, Roche (United Kingdom), Sahlgrenska University Hospital, Leiden University Medical Center, Centre National de la Recherche Scientifique, Sorbonne Université, Pitié-Salpêtrière Hospital, AXA Research Fund, Institut du Cerveau, Université Pierre-et-Marie-Curie, Technical University of Munich, University of Copenhagen, Rigshospitalet, Boehringer Ingelheim (United States), TUM Klinikum, Ludwig-Maximilians-Universität München, University of Eastern Finland, Kuopio University Hospital, Jagiellonian University, Piramal (Germany), New York University, University of Bonn, German Center for Neurodegenerative Diseases, Linköping University, King's College London, Charité – Universitätsmedizin Berlin, Universitätsmedizin Göttingen, University of Göttingen, Carol Davila University of Medicine and Pharmacy, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Science Foundation, U.S. Department of Defense, Foundation for the National Institutes of Health, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Biogen, University of Southern California, University of Pennsylvania, Medpace, Meso Scale Diagnostics, Synarc, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Itä-Suomen Yliopisto, National Research Centre, University of Pittsburgh, Sundhed og Sygdom, Det Frie Forskningsråd, Thomas Jefferson University, Science and Industry Endowment Fund, South London and Maudsley NHS Foundation Trust, Northern California Institute for Research and Education, EU Joint Programme – Neurodegenerative Disease Research, European Federation of Pharmaceutical Industries and Associations, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Australian Government, Lui Che Woo Institute of Innovative Medicine, TauRx Pharmaceuticals, York University, National Institute for Health and Care Research, Imperial College London, King's College London, European Commission, Bayer HealthCare, Deutsche Forschungsgemeinschaft, Universität Heidelberg, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Universiteit Leiden, Edith Cowan University, ZonMw, Radboud Universiteit, AXA Research Fund, Academy of Finland, Bundesministerium für Bildung und Forschung, Seoul National University, Sungkyunkwan University, Albert-Ludwigs-Universität Freiburg, Belgian Federal Science Policy Office, Gentofte Hospital, Dementia Collaborative Research Centres, Australia, Fonds Wetenschappelijk Onderzoek, Ministero della Salute, Lundbeckfonden, Eisai, KU Leuven, Karolinska Institutet, Kuopion Yliopistollinen Sairaala, Vetenskapsrådet, Centre National de la Recherche Scientifique, Leids Universitair Medisch Centrum, Rigshospitalet, National and Kapodistrian University of Athens, Deutsches Zentrum für Neurodegenerative Erkrankungen, Turun Yliopisto, Technische Universität München, Université Pierre et Marie Curie, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Universidade de Lisboa, Center for Translational Molecular Medicine, Radboud Universitair Medisch Centrum, Aristotle University of Thessaloniki, Universiteit Antwerpen, Universität zu Köln, Rheinische Friedrich-Wilhelms-Universität Bonn, Uniwersytet Medyczny im. Piastów Slaskich we Wroclawiu, Università degli Studi di Perugia, Innovative Medicines Initiative, Servier, Turun Yliopistollinen Keskussairaala, Vlaamse regering, Marcus och Amalia Wallenbergs minnesfond, Akershus Universitetssykehus, Merz Pharmaceuticals, H. Lundbeck A/S, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, IXICO, Région Normandie, Instituto de Investigación Marqués de Valdecilla, Fondation pour la Recherche sur Alzheimer, National Institutes of Health, Genentech, Samsung, University of California, San Diego, University of California, San Francisco, Avid Radiopharmaceuticals, Canadian Institutes of Health Research, Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis, Medical Research Council, National Health and Medical Research Council, Instituto de Salud Carlos III, Sahlgrenska Akademin, European Regional Development Fund, Krajowy Naukowy Osrodek Wiodacy, Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, Janssen Research and Development, Janssen Pharmaceuticals, Cilag
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OpenAlex ID: W2768948569