Journal article
Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- Jansen WJ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
- Ossenkoppele R Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands3Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the.
- Knol DL Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
- Tijms BM Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
- Scheltens P Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
- Verhey FR Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
- Visser PJ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands2Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience.
- Aalten P Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
- Aarsland D Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
- Alcolea D Roche Products, Welwyn Garden City, United Kingdom.
- Alexander M Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
- Almdahl IS Department of Neurology, University of Pennsylvania, Philadelphia.
- Arnold SE Center for Neuroscience and Cell Biology, Faculty of Medicine, Hospital Center University of Coimbra, Portugal.
- Baldeiras I Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
- Barthel H Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
- van Berckel BN GlaxoSmithKline, Worldwide Epidemiology, Research Triangle Park, North Carolina.
- Bibeau K Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
- Blennow K Division of Neuroscience, Medical Research Council Clinical Sciences Centre, Imperial College London, London, United Kingdom.
- Brooks DJ Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
- van Buchem MA CHRU de Tours, CIC INSERM 1415, INSERM U930, and Université François Rabelais de Tours, Tours, France.
- Camus V Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy20Sorbonne University, University Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) and Institut.
- Cavedo E Banner Alzheimer's Institute, Phoenix, Arizona.
- Chen K Institut National de la Santé et de la Recherche Médicale (Inserm), U1077, Caen, France.
- Chetelat G University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, Pennsylvania.
- Cohen AD Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
- Drzezga A Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
- Engelborghs S Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
- Fagan AM Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
- Fladby T Banner Alzheimer's Institute, Phoenix, Arizona27Eli Lilly, Indianapolis, Indiana28Department of Neurosciences, University of California, San Diego.
- Fleisher AS Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands6Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
- van der Flier WM Janssen Research and Development, Titusville, New Jersey.
- Ford L Department of Nuclear Medicine, Technischen Universitaet München, Munich, Germany.
- Förster S Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
- Fortea J Roche Products, Welwyn Garden City, United Kingdom.
- Foskett N Danish Dementia Research Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
- Frederiksen KS Department of Geriatrics, Institution of NVS, Section of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
- Freund-Levi Y Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy88Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals, and University of Geneva, Geneva, Switzerland.
- Frisoni GB Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- Froelich L Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
- Gabryelewicz T Postgraduate Institute of Medical Education and Research (PGIMER), Department of Biochemistry, Research Block-A, Chandigarh, India.
- Gill KD Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
- Gkatzima O Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain.
- Gómez-Tortosa E Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut.
- Gordon MF Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universitaet München, Munich, Germany.
- Grimmer T AXA Research Fund and UPMC ChairSorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer and INSERM U1127, Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital.
- Hampel H Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
- Hausner L Center of Geriatrics and Gerontology, University Hospital Freiburg, Freiburg, Germany.
- Hellwig S Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
- Herukka SK Center for Neurology, Hospital of Bremen-Ost, Bremen, Germany.
- Hildebrandt H GlaxoSmithKline, Worldwide Epidemiology, Epidemiology, Genetic Epidemiology and Neurology, United Kingdom.
- Ishihara L Memory Clinic and Neurochemistry Laboratory, Saint Luc University Hospital, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium.
- Ivanoiu A Helen Wills Neuroscience Institute, University of California, Berkeley.
- Jagust WJ Memory Clinic, Danish Dementia Research Center, Rigshospitalet, Copenhagen, Denmark.
- Johannsen P Postgraduate Institute of Medical Education and Research (PGIMER), Department of Biochemistry, Research Block-A, Chandigarh, India46Radiation Oncology, Emory University, Atlanta, Georgia.
- Kandimalla R First Department of Neurology, Neurochemistry Unit and Cognitive and Movement Disorders Clinic, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
- Kapaki E Jagiellonian University College of Medicine, Krakow, Poland.
- Klimkowicz-Mrowiec A University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, Pennsylvania.
- Klunk WE Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
- Köhler S Piramal Imaging, Berlin, Germany.
- Koglin N Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
- Kornhuber J Center for Cognitive Impairments, University Medical Centre Ljubljana, Ljubljana, Slovenia.
- Kramberger MG Department of Imaging and Pathology, Catholic University Leuven, Leuven, Belgium.
- Van Laere K Helen Wills Neuroscience Institute, University of California, Berkeley.
- Landau SM Department of Neuropsychiatry, Seoul National University, College of Medicine, Seoul, South Korea.
- Lee DY School of Medicine, Center for Brain Health, New York University, New York.
- de Leon M Section of Neurology, Center for Memory Disturbances, University of Perugia, Perugia, Italy.
- Lisetti V Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
- Lleó A Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark.
- Madsen K Department of Psychiatry and Psychotherapy, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
- Maier W Geriatric Medicine, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.
- Marcusson J Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden.
- Mattsson N Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Portugal.
- de Mendonça A Department of Geriatric Medicine, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
- Meulenbroek O Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
- Meyer PT Avid Radiopharmaceuticals, Philadelphia, Pennsylvania.
- Mintun MA Lui Che Woo Institute of Innovative Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
- Mok V Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Clinic University Hospital, Barcelona, Spain.
- Molinuevo JL Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
- Møllergård HM Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
- Morris JC Department of Neurodegeneration Diagnostics, Leading National Research Centre in Bialystok (KNOW), Medical University of Bialystok, Bialystok, Poland.
- Mroczko B Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
- Van der Mussele S Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Na DL Myrna Brind Center of Integrative Medicine, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania.
- Newberg A Dept NVS, Center for Alzheimer, Translational Alzheimer Neurobiology, Karolinska Institutet, and Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
- Nordberg A Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
- Nordlund A Janssen Research and Development, Titusville, New Jersey.
- Novak GP First Department of Neurology, Neurochemistry Unit and Cognitive and Movement Disorders Clinic, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
- Paraskevas GP Section of Neurology, Center for Memory Disturbances, University of Perugia, Perugia, Italy.
- Parnetti L Roche Products, Welwyn Garden City, United Kingdom69Department of Psychological Medicine, Institute of Psychiatry, Kings College London, London, United Kingdom.
- Perera G Department of Psychiatry and Psychotherapy, Charité Berlin, German Center for Neurodegenrative Diseases (DZNE), Berlin, Germany.
- Peters O Department of Psychiatry, Service of Old Age Psychiatry and Department of Clinical Neurosciences, Leenaards Memory Centre, University Hospital of Lausanne, Lausanne, Switzerland.
- Popp J Postgraduate Institute of Medical Education and Research (PGIMER), Department of Neurology, Nehru Hospital, Chandigarh, India.
- Prabhakar S Department of Neurology, Memory and Aging Center, University of California, San Francisco.
- Rabinovici GD Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
- Ramakers IH Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Clinic University Hospital, Barcelona, Spain.
- Rami L Center for Neuroscience and Cell Biology, Faculty of Medicine, Hospital Center University of Coimbra, Portugal.
- Resende de Oliveira C Turku PET Centre and Division of Clinical Neurosciences Turku, University of Turku and Turku University Hospital, Turku, Finland.
- Rinne JO Center for Vital Longevity, University of Texas at Dallas.
- Rodrigue KM Neurology Service, Universitary Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain.
- Rodríguez-Rodríguez E Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
- Roe CM Center for Cognitive Impairments, University Medical Centre Ljubljana, Ljubljana, Slovenia.
- Rot U Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
- Rowe CC Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany.
- Rüther E Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
- Sabri O Neurology Service, Universitary Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain.
- Sanchez-Juan P Center for Neuroscience and Cell Biology, Faculty of Medicine, Hospital Center University of Coimbra, Portugal.
- Santana I Neurologie de la Mémoire et du Langage, Centre Hospitalier Sainte-Anne, Université Paris 5, Paris, France.
- Sarazin M Sektion Gerontopsychiatrie, Universität Heidelberg, Heidelberg, Germany.
- Schröder J Center for Neurology, Hospital of Bremen-Ost, Bremen, Germany.
- Schütte C Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Seo SW Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
- Soetewey F Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
- Soininen H Department of Geriatrics-Gerontology-Gerontopsychiatry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
- Spiru L Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
- Struyfs H Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
- Teunissen CE Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
- Tsolaki M Laboratory for Cognitive Neurology and Alzheimer Research Centre KU Leuven, Catholic University Leuven, Leuven, Belgium.
- Vandenberghe R Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
- Verbeek MM Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
- Villemagne VL Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
- Vos SJ Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
- van Waalwijk van Doorn LJ Danish Dementia Research Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
- Waldemar G Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
- Wallin A Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden.
- Wallin ÅK Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany.
- Wiltfang J Department of Neurology, University of Pennsylvania, Philadelphia.
- Wolk DA Alzheimer Center, Wroclaw Medical University, Scinawa, Poland.
- Zboch M Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden87UCL Institute of Neurology, Queen Square, London, United Kingdom.
- Zetterberg H
- 2015-05-20
Published in:
- JAMA. - 2015
Adult
Age Factors
Aged
Aged, 80 and over
Amyloid beta-Peptides
Apolipoprotein E4
Biomarkers
Brain
Cerebrospinal Fluid
Cognitive Dysfunction
Dementia
Female
Genotype
Humans
Male
Middle Aged
Positron-Emission Tomography
Prevalence
Risk Factors
English
IMPORTANCE
Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
OBJECTIVE
To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).
DATA SOURCES
Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.
STUDY SELECTION
Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.
DATA EXTRACTION AND SYNTHESIS
Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.
MAIN OUTCOMES AND MEASURES
Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.
RESULTS
The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.
CONCLUSIONS AND RELEVANCE
Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.
Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
OBJECTIVE
To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).
DATA SOURCES
Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.
STUDY SELECTION
Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.
DATA EXTRACTION AND SYNTHESIS
Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.
MAIN OUTCOMES AND MEASURES
Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.
RESULTS
The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.
CONCLUSIONS AND RELEVANCE
Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1001/jama.2015.4668
- PMID 25988462
- Persistent URL
- https://sonar.ch/global/documents/52934
Statistics
Document views: 97
File downloads: