IMPORTANCE: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design. OBJECTIVE: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria. EXPOSURES: Alzheimer disease biomarkers detected on PET or in CSF. MAIN OUTCOMES AND MEASURES: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations. RESULTS: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18). CONCLUSIONS AND RELEVANCE: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

Acute Internal Medicine and Geriatrics Department of Health Medicine and Caring Sciences Linköping University Linköping Sweden

Aix Marseille Univ INSERM Institut de Neurosciences des Systèmes Marseille France

Aix Marseille University AP HM CNRS Centrale Marseille Institut Fresnel Timone Hospital Centre Européen de Recherche en Imagerie Médicale Nuclear Medicine Department Marseille France

Alzheimer Center Amsterdam Department of Neurology Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam University Medical Center Amsterdam the Netherlands

Alzheimer Centre Limburg Department of Psychiatry and Neuropsychology School for Mental Health and Neuroscience Maastricht University Maastricht the Netherlands

Alzheimer's Disease and Other Cognitive Disorders Unit Institut d'Investigacions Biomèdiques August Pi i Sunyer Clinic University Hospital Barcelona Spain

Alzheimer's Disease and Other Cognitive Disorders Unit Neurology Service Hospital Clínic of Barcelona IDIBAPS Barcelona Spain

Applied Biology Council of Scientific and Industrial Research Indian Institute of Chemical Technology Uppal Road Tarnaka Hyderabad Telangana State India

Aristotle University of Thessaloniki Memory and Dementia Center 3rd Department of Neurology George Papanicolau General Hospital of Thessaloniki Thessaloniki Greece

Assistance Publique Hôpitaux de Marseille Timone Service de Neurologie et Neuropsychologie Hôpital Timone Adultes Marseille France

Avid Radiopharmaceuticals Philadelphia Pennsylvania

Banner Alzheimer's Institute Phoenix Arizona

Biogen Cambridge Massachusetts

Brain and Mind Centre Faculty of Medicine and Health The University of Sydney Sydney New South Wales Australia

Brain Health Imaging Institute Department of Radiology Weill Cornell Medicine New York New York

BrainNow Research Institute Guangdong Province Shenzhen China

Center for Alzheimer Research and Treatment Department of Neurology Brigham and Women's Hospital Harvard Medical School Boston Massachusetts

Center for Neuroscience and Cell Biology University of Coimbra Coimbra Portugal

Center for Neurosciences Vrije Universiteit Brussel Brussels Belgium

Center for Research and Advanced Therapies Centro de Investigación y Ciencias Avanzadas Alzheimer Foundation Donostia San Sebastian Spain

Center for Research and Advanced Therapies CITA Alzheimer Foundation Donostia San Sebastian Spain

Center for Vital Longevity School of Behavioral and Brain Sciences The University of Texas at Dallas Dallas

Center of Neurology Department of Neurodegeneration and Hertie Institute for Clinical Brain Research University of Tuebingen Tuebingen Germany

Centre de Référence Démences Rares Pitié Salpêtrière University Hospital AP HP Paris France

Centre for Age Related Medicine Stavanger University Hospital Stavanger Norway

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas Madrid Spain

Centro Disturbi della Memoria Laboratorio di Neurochimica Clinica Clinica Neurologica Università di Perugia Perugia Italy

Chang Gung Memorial Foundation Linkou Taoyuan Taiwan

CIBERNED Network Center for Biomedical Research in Neurodegenerative Diseases National Institute of Health Carlos 3 Madrid Spain

Clinic for Neurogeriatrics and Neurological Rehabilitation University and Rehabilitation Hospital Ulm Ulm Germany

Clinical Memory Research Unit Department of Clinical Sciences Malmö Lund University Lund Sweden

Clinical Neurochemistry Laboratory Department of Neuroscience and Physiology Sahlgren's University Hospital Mölndal Sweden

Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden

Cognitive Neuroscience Division Department of Neurology and the Taub Institute Columbia University New York New York

Danish Dementia Research Center Department of Neurology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Biochemical Diagnostics University Hospital of Białystok Białystok Poland

Department of Biochemistry Kakatiya Medical College Mahatma Gandhi Memorial Hospital Warangal Telangana State India

Department of Biochemistry Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Biomedical and Pharmaceutical Sciences College of Pharmacy The University of Rhode Island Kingston

Department of Brain Sciences Imperial College London London United Kingdom

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Experimental Diagnostic and Specialty Medicine University of Bologna Bologna Spain

Department of Geriatric Psychiatry Central Institute of Mental Health Medical Faculty Mannheim University of Heidelberg Heidelberg Germany

Department of Geriatric Psychiatry University Hospital of Psychiatry Zürich and University of Zürich Zürich Switzerland

Department of Health Sciences University of Genoa Genoa Italy

Department of Imaging and Pathology Katholieke Universiteit Leuven Leuven Belgium

Department of Internal Medicine and Gerontology Faculty of Medicine Jagiellonian University Medical College Krakow Poland

Department of Molecular and Translational Medicine University of Brescia Brescia Italy

Department of Molecular Imaging Austin Health Melbourne Victoria Australia

Department of Neurobiology Care Sciences and Society Center for Alzheimer Research Division for Neurogeriatrics Karolinska Institutet Huddinge Sweden

Department of Neurobiology Care Sciences and Society Division of Clinical Geriatrics Karolinska Institutet Center for Alzheimer Research Stockholm Sweden

Department of Neurobiology Care Sciences and Society Karolinska Institutet Stockholm Sweden

Department of Neurodegeneration Diagnostics Medical University of Białystok Białystok Poland

Department of Neurodegenerative Disease University College London Queen Square Institute of Neurology Queen Square London United Kingdom

Department of Neurodegenerative Diseases and Geriatric Psychiatry University Hospital of Bonn Bonn Germany

Department of Neurodegenerative Diseases and Geriatric Psychiatry University of Bonn Bonn Germany

Department of Neurodegenerative Disorders Mossakowski Medical Research Centre Polish Academy of Sciences Warsaw Poland

Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Neurology Akershus University Hospital Lorenskog Norway

Department of Neurology Alzheimer Centre Amsterdam Amsterdam Neuroscience Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam the Netherlands

Department of Neurology and the Alzheimer's Disease Research Center Washington University School of Medicine in St Louis St Louis Missouri

Department of Neurology Chang Gung Memorial Hospital at Linkou Medical Center Chang Gung University College of Medicine Taoyuan Taiwan

Department of Neurology Cliniques Universitaires Saint Luc Brussels Belgium

Department of Neurology Fundación Jiménez Díaz Madrid Spain

Department of Neurology Institut de la Mémoire et de la Maladie d'Alzheimer Centre de Référence Démences Rares Hôpital de la Pitié Salpêtrière Assistance Publique Hôpitaux de Paris Paris France

Department of Neurology Institute of Clinical Medicine University of Eastern Finland Kuopio Finland

Department of Neurology Medical Center Zaloska 7 Ljubljana Slovenia

Department of Neurology Nehru Hospital Postgraduate Institute of Medical Education and Research Chandigarh India

Department of Neurology of Memory and Language Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences Hôpital Sainte Anne F 75014 Paris France

Department of Neurology Osaka City University Graduate School of Medicine Osaka Japan

Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

Department of Neurology Sungkyunkwan University School of Medicine Samsung Medical Center Seoul South Korea

Department of Neurology Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University Irving Medical Center New York New York

Department of Neurology University Hospital Basel Basel Switzerland

Department of Neurology University Hospital Leiden Leiden the Netherlands

Department of Neurology University Hospital of Trondheim Trondheim Norway

Department of Neurology University Medical Centre Ljubljana Ljubljana Slovenia

Department of Neurology University of Pennsylvania Philadelphia

Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania

Department of Neurology Washington University School of Medicine in St Louis St Louis Missouri

Department of Neuropsychiatry Seoul National University Hospital Seoul South Korea

Department of Neuroscience Faculty of Medicine Norwegian University of Science and Technology Trondheim Norway

Department of Nuclear Medicine and Molecular Imaging Center Linkou Chang Gung Memorial Hospital Guishan Taoyuan Taiwan

Department of Nuclear Medicine Klinikum Bayreuth Bayreuth Germany

Department of Nuclear Medicine Klinikum rechts der Isar Technische Universität München Munich Germany

Department of Nuclear Medicine Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Department of Nuclear Medicine Positron Emission Tomography Centre Aarhus University Aarhus Denmark

Department of Nuclear Medicine University Hospital of Cologne Cologne Germany

Department of Nuclear Medicine University Hospital of Leipzig Leipzig Germany

Department of Old Age Psychiatry Psychology and Neuroscience King's College London London United Kingdom

Department of Psychiatry and Human Behavior Alpert Medical School of Brown University Providence Rhode Island

Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden

Department of Psychiatry and Psychotherapy Klinikum rechts der Isar Technical University of Munich School of Medicine Munich Germany

Department of Psychiatry and Psychotherapy Medical Center Faculty of Medicine University of Freiburg Freiburg Germany

Department of Psychiatry and Psychotherapy University Hospital Friedrich Alexander University Erlangen Nuremberg Erlangen Germany

Department of Psychiatry and Psychotherapy University Medical Center Georg August University Göttingen Germany

Department of Psychiatry and Psychotherapy University Medical Center Göttingen Göttingen Germany

Department of Psychiatry Faculty of Medicine McGill University Montreal Quebec Canada

Department of Psychiatry Massachusetts General Hospital Boston

Department of Psychiatry Medical Faculty University of Cologne Cologne Germany

Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh Pennsylvania

Department of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden

Department of Radiation Oncology Emory University Atlanta Georgia

Department of Radiology and Nuclear Medicine Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam the Netherlands

Department of Radiology Massachusetts General Hospital Boston

Department of Radiology Perelman School of Medicine University of Pennsylvania Philadelphia

Departments of Neurology and Laboratory Medicine Radboud University Medical Center Donders Institute for Brain Cognition and Behaviour Radboud Alzheimer Centre Nijmegen the Netherlands

Deutsches Zentrum für Neurodegenerative Erkrankungen e 5 Bonn Germany

DIMES University of Bologna Bologna Italy

DINOGMI University of Genoa Genoa Italy

Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno Infantili University of Genoa Genoa Italy

Division of Geriatrics University of Goettingen Medical School Goettingen Germany

Division of Infectious Diseases and Immunology University of Massachusetts Medical School Worcester

Division of Molecular Biophysics and Integrated Bioimaging Lawrence Berkeley National Laboratory Berkeley California

Division of Neurology Department of Medicine and Therapeutics Prince of Wales Hospital Faculty of Medicine The Chinese University of Hong Kong Hong Kong China

Division of Nuclear Medicine and Molecular Imaging University Hospitals Leuven Leuven Belgium

Douglas Mental Health University Institute Montreal Quebec Canada

DZNE Bonn Germany

Eli Lilly and Company Indianapolis Indiana

Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases University of Cologne Cologne Germany

Faculty of Medicine University of Coimbra Azinhaga de Santa Comba Coimbra Portugal

Faculty of Medicine University of Lisboa Lisboa Portugal

Florey Department of Neuroscience University of Melbourne Melbourne Victoria Australia

Geriatrics Gerontology and Old Age Psychiatry Clinical Department Carol Davila University of Medicine and Pharmacy Elias Emergency Clinical Hospital Bucharest Romania

Greek Association of Alzheimer's Disease and Related Disorders Thessaloniki Greece

Harvard Aging Brain Study Department of Neurology Harvard Medical School Boston Massachusetts

Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences College of Medicine Chang Gung University Taoyuan Taiwan

Helen Wills Neuroscience Institute University of California Berkeley Berkeley

Hong Kong Center for Neurodegenerative Diseases Hong Kong China

Institute of Clinical Medicine Neurology University of Eastern Finland Kuopio Finland

Istituto delle Scienze Neurologiche di Bologna IRCCS Bologna Italy

Klinik für Psychiatrie und Psychotherapie Charité Universitätsmedizin Berlin CBF Berlin Deutschland

Klinik und Poliklinik für Psychiatrie und Psychotherapie Universitätsklinikum Leipzig Leipzig Germany

Klinikum Bremen Ost University of Oldenburg Institute of Psychology Oldenburg Germany

Laboratory Alzheimer's Neuroimaging and Epidemiology Istituto di Ricovero e Cura a Carattere Scientifico Fatebenefratelli Brescia Italy

Laboratory for Cognitive Neurology Department of Neurosciences University of Leuven Leuven Belgium

Life Molecular Imaging GmbH Berlin Germany

Margaret K L Cheung Research Centre for Management of Parkinsonism Gerald Choa Neuroscience Centre Lui Che Woo Institute of Innovative Medicine The Chinese University of Hong Kong Hong Kong China

McConnell Brain Imaging Centre Montreal Neurological Institute Montreal Quebec Canada

Memory and Aging Center Department of Neurology University of California San Francisco San Francisco

Memory Clinic and Longevity Medicine Ana Aslan International Foundation Bucharest Romania

Memory Clinic Department of Geriatrics Uppsala University Hospital Uppsala Sweden

Memory Clinic University Department of Geriatric Medicine Felix Platter Hospital Basel Switzerland

Memory Clinic University Hospitals and University of Geneva Geneva Switzerland

Memory Disorder Unit Copenhagen University Hospital Copenhagen Denmark

Memory Unit Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona Spain

Molecular Biomarkers in Psychiatry University of Pittsburgh Pittsburgh Pennsylvania

Myrna Brind Center of Integrative Medicine Thomas Jefferson University and Hospital Philadelphia Pennsylvania

National and Kapodistrian University of Athens School of Medicine 1st Department of Neurology Eginition Hospital Athens Greece

Neurobiology Research Unit Copenhagen University Hospital Copenhagen Denmark

Neurocenter Department of Neurology Kuopio University Hospital Kuopio Finland

Neurocenter Neurology Kuopio University Hospital Kuopio Finland

Neurology Department and Laboratory of Neurochemistry Centro Hospitalar e Universitário de Coimbra Praceta Professor Mota Pinto Coimbra Portugal

Neurology Department Hospital Universitario Marqués de Valdecilla and IDIVAL Santander Spain

Neurology Department University Hospitals Leuven Leuven Belgium

Neuropsychiatric Epidemiology Unit Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

Neuroscience Center Samsung Medical Center Seoul South Korea

Normandie University University of Caen Normandie Institut Blood and Brain at Caen Normandie Cyceron Caen France

Nuclear Medicine Department University Hospital Marqués de Valdecilla Molecular Imaging Instituto de Investigación Sanitaria Valdecilla University of Cantabria Santander Spain

Old Age Psychiatry Department of Psychiatry University Hospital of Lausanne and University of Lausanne Lausanne Switzerland

Ospedale Policlinico San Martino IRCCS Genoa Italy

Radboudumc Alzheimer Centre Radboud University Medical Center Nijmegen the Netherlands

Reference Center for Biological Markers of Dementia University of Antwerp Antwerp Belgium

Research Center and Memory Clinic of Fundació Alzheimer Centre Educacional Institut Català de Neurociències Aplicades Universitat Internacional de Catalunya Barcelona Spain

Research Scientific Didactic Centre of Dementia Related Diseases in Scinawa Medical University of Wroclaw Wroclaw Poland

School of Medical Sciences Örebro University Örebro Sweden

School of Psychology Faculty of Science The University of Sydney Sydney New South Wales Australia

Section for Geriatric Psychiatry University of Heidelberg Heidelberg Germany

Service of Neurology University Hospital Marqués de Valdecilla IDIVAL CIBERNED Santander Spain

Sorbonne University Clinical Research Group no 21 Alzheimer Precision Medicine AP HP Pitié Salpêtrière Hospital Paris France

Studies on Prevention of Alzheimer's Disease Centre Montreal Quebec Canada

Translational and Clinical Research Institute University of Newcastle upon Tyne United Kingdom

Translational Neuroscience Laboratory McLean Hospital Harvard Medical School Belmont Massachusetts

Turku PET Centre Turku Finland

Turku PET Centre University of Turku Turku Finland

UK Dementia Research Institute London United Kingdom

Unite Mixte de Recherche INSERM U930 French National Centre for Scientific Research ERL Tours France

Universität Heidelberg Abteilung Gerontopsychiatrie Zentralinstitut für Seelische Gesundheit Mannheim Mannheim Germany

Université de Paris Paris Université Paris Saclay BioMaps CEA CNRS INSERM Orsay France

Université Paris Saclay Service Hospitalier Frédéric Joliot BioMaps Service Hospitalier Frederic Joliot Orsay France

Comment In

JAMA Neurol. 2022 Mar 1;79(3):225-227. doi: 10.1001/jamaneurol.2021.5225. PubMed

Erratum In

JAMA Neurol. 2022 Mar 1;79(3):313. doi: 10.1001/jamaneurol.2022.0265. PubMed

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