Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/18339
Title: Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
Authors: Jansen, Willemijn J;Ossenkoppele, Rik;Tijms, Betty M;Fagan, Anne M;Hansson, Oskar;Klunk, William E;van der Flier, Wiesje M;Villemagne, Victor L;Frisoni, Giovanni B;Fleisher, Adam S;Lleó, Alberto;Teunissen, Charlotte E;Vos, Stephanie J B;van Waalwijk van Doorn, Linda J C;Waldemar, Gunhild;Wallin, Åsa K;Wiltfang, Jens;Zetterberg, Henrik;Wallin, Anders;Engelborghs, Sebastiaan;Na, Duk L;Fladby, Tormod;Chételat, Gäel;Molinuevo, José Luis;Landau, Susan M;Mattsson, Niklas;Kornhuber, Johannes;Sabri, Osama;Rowe, Christopher C;Parnetti, Lucilla;Popp, Julius;Jagust, William J;Aalten, Pauline;Lee, Dong Young;Vandenberghe, Rik;Resende de Oliveira, Catarina;Kapaki, Elisabeth;Froelich, Lutz;Ivanoiu, Adrian;Gabryelewicz, Tomasz;de Mendonça, Alexandre;Verbeek, Marcel M;Sanchez-Juan, Páscual;Hildebrandt, Helmut;Camus, Vincent;Zboch, Marzena;Brooks, David J;Drzezga, Alexander;Rinne, Juha O;Newberg, Andrew;Sarazin, Marie;Rabinovici, Gil D;Madsen, Karine;Kramberger, Milica G;Nordberg, Agneta;Mok, Vincent;Mroczko, Barbara;Wolk, David A;Meyer, Philipp T;Baldeiras, Inês;Tsolaki, Magda;Scheltens, Philip;Verhey, Frans R J;Visser, Pieter Jelle;Aarsland, Dag;Alcolea, Daniel;Alexander, Myriam;Almdahl, Ina S;Arnold, Steven E;Barthel, Henryk;van Berckel, Bart N M;Blennow, Kaj;van Buchem, Mark A;Cavedo, Enrica;Chen, Kewei;Chipi, Elena;Cohen, Ann D;Förster, Stefan;Herukka, Sanna-Kaisa;Fortea, Juan;Frederiksen, Kristian S;Freund-Levi, Yvonne;Gkatzima, Olymbia;Gordon, Mark Forrest;Grimmer, Timo;Hampel, Harald;Hausner, Lucrezia;Hellwig, Sabine;Johannsen, Peter;Klimkowicz-Mrowiec, Aleksandra;Köhler, Sebastian;Koglin, Norman;van Laere, Koen;de Leon, Mony;Lisetti, Viviana;Maier, Wolfgang;Marcusson, Jan;Rami, Lorena;Meulenbroek, Olga;Møllergård, Hanne M;Morris, John C;Nordlund, Arto;Novak, Gerald P;Paraskevas, George P;Perera, Gayan;Peters, Oliver;Ramakers, Inez H G B;Rodríguez-Rodríguez, Eloy;Roe, Catherine M;Rot, Uros;Rüther, Eckart;Santana, Isabel;Schröder, Johannes;Seo, Sang W;Soininen, Hilkka;Spiru, Luiza;Mintun, Mark A;Stomrud, Erik;Struyfs, Hanne
Affiliation: UCL Institute of Neurology, Queen Square, London, United Kingdom
Department of Nuclear Medicine, Technische Universitaet München, Munich, Germany
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands
Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands
Helen Wills Neuroscience Institute, University of California, Berkeley
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals, and University of Geneva, Geneva, Switzerland
Banner Alzheimer's Institute, Phoenix, Arizona
Eli Lilly and Company, Indianapolis, Indiana
Department of Neurosciences, University of California, San Diego
Neurology Department, Hospital de Sant Pau, Barcelona, Spain
Avid Radiopharmaceuticals, Philadelphia, Pennsylvania
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Caen, Caen, France
Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Clinic University Hospital, Barcelona, Spain
Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany
Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri
Department of Psychiatry, Service of Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland
Department of Neuropsychiatry, Seoul National University, College of Medicine, Seoul, South Korea
Laboratory for Cognitive Neurology and Alzheimer Research Centre KU Leuven, Catholic University Leuven, Leuven, Belgium
First Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Memory Clinic and Neurochemistry Laboratory, Saint Luc University Hospital, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium
Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland
Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands
Neurology Service, Universitary Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain
Center for Neurology, Hospital of Bremen-Ost, Bremen, Germany
CHRU de Tours, CIC INSERM 1415, INSERM U930, and Université François Rabelais de Tours, Tours, France
Alzheimer Center, Wroclaw Medical University, Scinawa, Poland
Division of Neuroscience, Medical Research Council Clinical Sciences Centre, Imperial College London, London, England
Department of Nuclear Medicine, University of Cologne, Cologne, Germany
Turku PET Centre and Division of Clinical Neurosciences Turku, University of Turku and Turku University Hospital, Turku, Finland
Myrna Brind Center of Integrative Medicine, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania
Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Neurologie de la Mémoire et du Langage, Centre Hospitalier Sainte-Anne, Université Paris 5, Paris, France
Department of Neurology, Memory and Aging Center, University of California, San Francisco
Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark
Center for Cognitive Impairments, University Medical Centre Ljubljana, Ljubljana, Slovenia
Department NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, and Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden
Lui Che Woo Institute of Innovative Medicine, Department of Medicine and Therapeutics, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Hong Kong
Department of Neurodegeneration Diagnostics, Leading National Research Centre in Białystok (KNOW), Medical University of Białystok, Białystok, Poland
Department of Neurology, University of Pennsylvania, Philadelphia
Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands
Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway
Roche Products, Welwyn Garden City, United Kingdom
Department of Neurology, Akershus University Hospital, Lørenskog, Norway
Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Stijmsalpêtrière, Boulevard de l'hôpital, F-75013, Paris, France
AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière, Paris, France
Section of Neurology, Center for Memory Disturbances, University of Perugia, Perugia, Italy
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Danish Dementia Research Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark
Department of Geriatrics, Karolinska University Hospital Huddinge, Section of Clinical Geriatrics, Institution of NVS, Karolinska Institutet, Stockholm, Sweden
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut
Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universitaet München, Munich, Germany
AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière, Paris, France
Department of Psychiatry, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Ludwig-Maximilian University, Munich, Germany
Center of Geriatrics and Gerontology, University Hospital Freiburg, Freiburg, Germany
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
Memory Clinic, Danish Dementia Research Center, Rigshospitalet, Copenhagen, Denmark
Jagiellonian University College of Medicine, Krakow, Poland
Piramal Imaging GmbH, Berlin, Germany
Department of Imaging and Pathology, Catholic University Leuven, Leuven, Belgium
School of Medicine, Center for Brain Health, New York University, New York
Department of Psychiatry and Psychotherapy, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Geriatric Medicine, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden
Department of Geriatric Medicine, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands
Janssen Research and Development, Titusville, New Jersey
Department of Psychological Medicine, Institute of Psychiatry, Kings College London, London, United Kingdom
Department of Psychiatry and Psychotherapy, Charité Berlin, German Center for Neurodegenrative Diseases (DZNE), Berlin, Germany
Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany
Center for Neuroscience and Cell Biology, Faculty of Medicine, Centro Hospitalar e Universitário de Coimbra, Portugal
Sektion Gerontopsychiatrie, Universität Heidelberg, Heidelberg, Germany
Department of Geriatrics-Gerontology-Gerontopsychiatry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden
Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands
Issue Date: 1-Jan-2018
Citation: JAMA psychiatry 2018; 75(1): 84-95
Abstract: 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. To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia. 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. 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. 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. 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/18339
DOI: 10.1001/jamapsychiatry.2017.3391
ORCID: 0000-0003-3910-2453
PubMed URL: 29188296
Type: Journal Article
Appears in Collections:Journal articles

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