Jansen, Willemijn J; Ossenkoppele, Rik; Knol, Dirk L; Tijms, Betty M; Scheltens, Philip; Verhey, Frans R J; Visser, Pieter Jelle; Aalten, Pauline; Aarsland, Dag; Alcolea, Daniel; Alexander, Myriam; Almdahl, Ina S; Arnold, Steven E; Baldeiras, Ines; Barthel, Henryk; van Berckel, Bart N M; Bibeau, Kristen; Blennow, Kaj; Brooks, David J; van Buchem, Mark A; Camus, Vincent; Cavedo, Enrica; Chen, Kewei; Chetelat, Gael; Cohen, Ann D; Drzezga, Alexander; Engelborghs, Sebastiaan; Fagan, Anne M; Fladby, Tormod; Fleisher, Adam S; van der Flier, Wiesje M; Ford, Lisa; Forster, Stefan; Fortea, Juan; Foskett, Nadia; Frederiksen, Kristian S; Freund-Levi, Yvonne; Frisoni, Giovanni B; Froelich, Lutz; Gabryelewicz, Tomasz; Gill, Kiran Dip; Gkatzima, Olymbia; Gomez-Tortosa, Estrella; Gordon, Mark Forrest; Grimmer, Timo; Hampel, Harald; Hausner, Lucrezia; Hellwig, Sabine; Herukka, Sanna-Kaisa; Hildebrandt, Helmut; Ishihara, Lianna; Ivanoiu, Adrian; Jagust, William J; Johannsen, Peter; Kandimalla, Ramesh; Kapaki, Elisabeth; Klimkowicz-Mrowiec, Aleksandra; Klunk, William E; Kohler, Sebastian; Koglin, Norman; Kornhuber, Johannes; Kramberger, Milica G; Van Laere, Koen; Landau, Susan M; Lee, Dong Young; de Leon, Mony; Lisetti, Viviana; Lleo, Alberto; Madsen, Karine; Maier, Wolfgang; Marcusson, Jan; Mattsson, Niklas; de Mendonca, Alexandre; Meulenbroek, Olga; Meyer, Philipp T; Mintun, Mark A; Mok, Vincent; Molinuevo, Jose Luis; Mollergard, Hanne M; Morris, John C; Mroczko, Barbara; Van der Mussele, Stefan; Na, Duk L; Newberg, Andrew; Nordberg, Agneta; Nordlund, Arto; Novak, Gerald P; Paraskevas, George P; Parnetti, Lucilla; Perera, Gayan; Peters, Oliver; Popp, Julius; Prabhakar, Sudesh; Rabinovici, Gil D; Ramakers, Inez H G B; Rami, Lorena; Resende de Oliveira, Catarina; Rinne, Juha O; Rodrigue, Karen M; Rodriguez-Rodriguez, Eloy; Roe, Catherine M; Rot, Uros; Rowe, Christopher C; Ruther, Eckart; Sabri, Osama; Sanchez-Juan, Pascual; Santana, Isabel; Sarazin, Marie; Schroder, Johannes; Schutte, Christin; Seo, Sang W; Soetewey, Femke; Soininen, Hilkka; Spiru, Luiza; Struyfs, Hanne; Teunissen, Charlotte E; Tsolaki, Magda; Vandenberghe, Rik; Verbeek, Marcel M; Villemagne, Victor L; Vos, Stephanie J B; van Waalwijk van Doorn, Linda J C; Waldemar, Gunhild; Wallin, Anders; Wallin, Asa K; Wiltfang, Jens; Wolk, David A; Zboch, Marzena; Zetterberg, Henrik
JAMA
2015May ; 313 ( 19 ) :1924-38.
PMID : 25988462
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Jansen, Willemijn J - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Ossenkoppele, Rik - 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, Dirk L - Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
Tijms, Betty M - Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Scheltens, Philip - Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Verhey, Frans R J - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Visser, Pieter Jelle - 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. CN - Amyloid Biomarker Study Group
Aalten, Pauline - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Aarsland, Dag - Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
Alcolea, Daniel - Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
Alexander, Myriam - Roche Products, Welwyn Garden City, United Kingdom.
Almdahl, Ina S - Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
Arnold, Steven E - Department of Neurology, University of Pennsylvania, Philadelphia.
Baldeiras, Ines - Center for Neuroscience and Cell Biology, Faculty of Medicine, Hospital Center University of Coimbra, Portugal.
Barthel, Henryk - Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
van Berckel, Bart N M - Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Bibeau, Kristen - GlaxoSmithKline, Worldwide Epidemiology, Research Triangle Park, North Carolina.
Blennow, Kaj - Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden.
Brooks, David J - Division of Neuroscience, Medical Research Council Clinical Sciences Centre, Imperial College London, London, United Kingdom.
van Buchem, Mark A - Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Camus, Vincent - CHRU de Tours, CIC INSERM 1415, INSERM U930, and Universite Francois Rabelais de Tours, Tours, France.
Cavedo, Enrica - 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 Memoire et de la Maladie d'Alzheimer (IM2A) and Institut.
Chen, Kewei - Banner Alzheimer's Institute, Phoenix, Arizona.
Chetelat, Gael - Institut National de la Sante et de la Recherche Medicale (Inserm), U1077, Caen, France.
Cohen, Ann D - University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, Pennsylvania.
Drzezga, Alexander - Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
Engelborghs, Sebastiaan - Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
Fagan, Anne M - Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
Fladby, Tormod - Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
Fleisher, Adam S - Banner Alzheimer's Institute, Phoenix, Arizona27Eli Lilly, Indianapolis, Indiana28Department of Neurosciences, University of California, San Diego.
van der Flier, Wiesje M - 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.
Ford, Lisa - Janssen Research and Development, Titusville, New Jersey.
Forster, Stefan - Department of Nuclear Medicine, Technischen Universitaet Munchen, Munich, Germany.
Fortea, Juan - Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
Foskett, Nadia - Roche Products, Welwyn Garden City, United Kingdom.
Frederiksen, Kristian S - Danish Dementia Research Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
Freund-Levi, Yvonne - Department of Geriatrics, Institution of NVS, Section of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Frisoni, Giovanni B - 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.
Froelich, Lutz - Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Gabryelewicz, Tomasz - Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
Gill, Kiran Dip - Postgraduate Institute of Medical Education and Research (PGIMER), Department of Biochemistry, Research Block-A, Chandigarh, India.
Gkatzima, Olymbia - Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Gomez-Tortosa, Estrella - Department of Neurology, Fundacion Jimenez Diaz, Madrid, Spain.
Gordon, Mark Forrest - Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut.
Grimmer, Timo - Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universitaet Munchen, Munich, Germany.
Hampel, Harald - AXA Research Fund and UPMC ChairSorbonne Universites, Universite Pierre et Marie Curie, Paris 06, Institut de la Memoire et de la Maladie d'Alzheimer and INSERM U1127, Institut du Cerveau et de la Moelle epiniere (ICM), Departement de Neurologie, Hopital.
Hausner, Lucrezia - Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Hellwig, Sabine - Center of Geriatrics and Gerontology, University Hospital Freiburg, Freiburg, Germany.
Herukka, Sanna-Kaisa - Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Hildebrandt, Helmut - Center for Neurology, Hospital of Bremen-Ost, Bremen, Germany.
Ishihara, Lianna - GlaxoSmithKline, Worldwide Epidemiology, Epidemiology, Genetic Epidemiology and Neurology, United Kingdom.
Ivanoiu, Adrian - Memory Clinic and Neurochemistry Laboratory, Saint Luc University Hospital, Institute of Neuroscience, Universite catholique de Louvain, Brussels, Belgium.
Jagust, William J - Helen Wills Neuroscience Institute, University of California, Berkeley.
Johannsen, Peter - Memory Clinic, Danish Dementia Research Center, Rigshospitalet, Copenhagen, Denmark.
Kandimalla, Ramesh - Postgraduate Institute of Medical Education and Research (PGIMER), Department of Biochemistry, Research Block-A, Chandigarh, India46Radiation Oncology, Emory University, Atlanta, Georgia.
Kapaki, Elisabeth - First Department of Neurology, Neurochemistry Unit and Cognitive and Movement Disorders Clinic, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
Klimkowicz-Mrowiec, Aleksandra - Jagiellonian University College of Medicine, Krakow, Poland.
Klunk, William E - University of Pittsburgh School of Medicine, Department of Psychiatry, Pittsburgh, Pennsylvania.
Kohler, Sebastian - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Koglin, Norman - Piramal Imaging, Berlin, Germany.
Kornhuber, Johannes - Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
Kramberger, Milica G - Center for Cognitive Impairments, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Van Laere, Koen - Department of Imaging and Pathology, Catholic University Leuven, Leuven, Belgium.
Landau, Susan M - Helen Wills Neuroscience Institute, University of California, Berkeley.
Lee, Dong Young - Department of Neuropsychiatry, Seoul National University, College of Medicine, Seoul, South Korea.
de Leon, Mony - School of Medicine, Center for Brain Health, New York University, New York.
Lisetti, Viviana - Section of Neurology, Center for Memory Disturbances, University of Perugia, Perugia, Italy.
Lleo, Alberto - Neurology Department, Hospital de Sant Pau, Barcelona, Spain.
Madsen, Karine - Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark.
Maier, Wolfgang - Department of Psychiatry and Psychotherapy, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Marcusson, Jan - Geriatric Medicine, Department of Clinical and Experimental Medicine, University of Linkoping, Linkoping, Sweden.
Mattsson, Niklas - Clinical Memory Research Unit, Clinical Sciences Malmo, Lund University, Lund, Sweden.
de Mendonca, Alexandre - Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Portugal.
Meulenbroek, Olga - Department of Geriatric Medicine, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
Meyer, Philipp T - Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
Mintun, Mark A - Avid Radiopharmaceuticals, Philadelphia, Pennsylvania.
Mok, Vincent - Lui Che Woo Institute of Innovative Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
Molinuevo, Jose Luis - Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Clinic University Hospital, Barcelona, Spain.
Mollergard, Hanne M - Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
Morris, John C - Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
Mroczko, Barbara - Department of Neurodegeneration Diagnostics, Leading National Research Centre in Bialystok (KNOW), Medical University of Bialystok, Bialystok, Poland.
Van der Mussele, Stefan - Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
Na, Duk L - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Newberg, Andrew - Myrna Brind Center of Integrative Medicine, Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania.
Nordberg, Agneta - Dept NVS, Center for Alzheimer, Translational Alzheimer Neurobiology, Karolinska Institutet, and Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
Nordlund, Arto - Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden.
Novak, Gerald P - Janssen Research and Development, Titusville, New Jersey.
Paraskevas, George P - First Department of Neurology, Neurochemistry Unit and Cognitive and Movement Disorders Clinic, National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece.
Parnetti, Lucilla - Section of Neurology, Center for Memory Disturbances, University of Perugia, Perugia, Italy.
Perera, Gayan - Roche Products, Welwyn Garden City, United Kingdom69Department of Psychological Medicine, Institute of Psychiatry, Kings College London, London, United Kingdom.
Peters, Oliver - Department of Psychiatry and Psychotherapy, Charite Berlin, German Center for Neurodegenrative Diseases (DZNE), Berlin, Germany.
Popp, Julius - Department of Psychiatry, Service of Old Age Psychiatry and Department of Clinical Neurosciences, Leenaards Memory Centre, University Hospital of Lausanne, Lausanne, Switzerland.
Prabhakar, Sudesh - Postgraduate Institute of Medical Education and Research (PGIMER), Department of Neurology, Nehru Hospital, Chandigarh, India.
Rabinovici, Gil D - Department of Neurology, Memory and Aging Center, University of California, San Francisco.
Ramakers, Inez H G B - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Rami, Lorena - Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Clinic University Hospital, Barcelona, Spain.
Resende de Oliveira, Catarina - Center for Neuroscience and Cell Biology, Faculty of Medicine, Hospital Center University of Coimbra, Portugal.
Rinne, Juha O - Turku PET Centre and Division of Clinical Neurosciences Turku, University of Turku and Turku University Hospital, Turku, Finland.
Rodrigue, Karen M - Center for Vital Longevity, University of Texas at Dallas.
Rodriguez-Rodriguez, Eloy - Neurology Service, Universitary Hospital Marques de Valdecilla, IDIVAL, Santander, Spain.
Roe, Catherine M - Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, Missouri.
Rot, Uros - Center for Cognitive Impairments, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Rowe, Christopher C - Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
Ruther, Eckart - Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Gottingen, Germany.
Sabri, Osama - Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.
Sanchez-Juan, Pascual - Neurology Service, Universitary Hospital Marques de Valdecilla, IDIVAL, Santander, Spain.
Santana, Isabel - Center for Neuroscience and Cell Biology, Faculty of Medicine, Hospital Center University of Coimbra, Portugal.
Sarazin, Marie - Neurologie de la Memoire et du Langage, Centre Hospitalier Sainte-Anne, Universite Paris 5, Paris, France.
Schroder, Johannes - Sektion Gerontopsychiatrie, Universitat Heidelberg, Heidelberg, Germany.
Schutte, Christin - Center for Neurology, Hospital of Bremen-Ost, Bremen, Germany.
Seo, Sang W - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Soetewey, Femke - Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
Soininen, Hilkka - Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Spiru, Luiza - Department of Geriatrics-Gerontology-Gerontopsychiatry, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Struyfs, Hanne - Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
Teunissen, Charlotte E - Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
Tsolaki, Magda - Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Vandenberghe, Rik - Laboratory for Cognitive Neurology and Alzheimer Research Centre KU Leuven, Catholic University Leuven, Leuven, Belgium.
Verbeek, Marcel M - Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
Villemagne, Victor L - Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Australia.
Vos, Stephanie J B - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
van Waalwijk van Doorn, Linda J C - Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands.
Waldemar, Gunhild - Danish Dementia Research Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
Wallin, Anders - Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden.
Wallin, Asa K - Clinical Memory Research Unit, Clinical Sciences Malmo, Lund University, Lund, Sweden.
Wiltfang, Jens - Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Gottingen, Germany.
Wolk, David A - Department of Neurology, University of Pennsylvania, Philadelphia.
Zboch, Marzena - Alzheimer Center, Wroclaw Medical University, Scinawa, Poland.
Zetterberg, Henrik - Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden87UCL Institute of Neurology, Queen Square, London, United Kingdom.
ABSTRACT
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.
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MESH
Adult, Age Factors, Aged, Aged, 80 and over, Amyloid beta-Peptides/*analysis, Apolipoprotein E4/*genetics, Biomarkers/analysis, Brain/*pathology, Cerebrospinal Fluid/chemistry, Dementia/pathology, Female, Genotype, Humans, Male, Middle Aged, Mild Cognitive Impairment/*pathology, Positron-Emission Tomography, Prevalence, Risk Factors
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