Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis
Willemijn J Jansen, Rik Ossenkoppele, Dirk L Knol, Betty M Tijms, Philip Scheltens, Frans R J Verhey, Pieter Jelle Visser, Amyloid Biomarker Study Group, Pauline Aalten, Dag Aarsland, Daniel Alcolea, Myriam Alexander, Ina S Almdahl, Steven E Arnold, Inês Baldeiras, Henryk Barthel, Bart N M van Berckel, Kristen Bibeau, Kaj Blennow, David J Brooks, Mark A van Buchem, Vincent Camus, Enrica Cavedo, Kewei Chen, Gael Chetelat, Ann D Cohen, Alexander Drzezga, Sebastiaan Engelborghs, Anne M Fagan, Tormod Fladby, Adam S Fleisher, Wiesje M van der Flier, Lisa Ford, Stefan Förster, Juan Fortea, Nadia Foskett, Kristian S Frederiksen, Yvonne Freund-Levi, Giovanni B Frisoni, Lutz Froelich, Tomasz Gabryelewicz, Kiran Dip Gill, Olymbia Gkatzima, Estrella Gómez-Tortosa, Mark Forrest Gordon, Timo Grimmer, Harald Hampel, Lucrezia Hausner, Sabine Hellwig, Sanna-Kaisa Herukka, Helmut Hildebrandt, Lianna Ishihara, Adrian Ivanoiu, William J Jagust, Peter Johannsen, Ramesh Kandimalla, Elisabeth Kapaki, Aleksandra Klimkowicz-Mrowiec, William E Klunk, Sebastian Köhler, Norman Koglin, Johannes Kornhuber, Milica G Kramberger, Koen Van Laere, Susan M Landau, Dong Young Lee, Mony de Leon, Viviana Lisetti, Alberto Lleó, Karine Madsen, Wolfgang Maier, Jan Marcusson, Niklas Mattsson, Alexandre de Mendonça, Olga Meulenbroek, Philipp T Meyer, Mark A Mintun, Vincent Mok, José Luis Molinuevo, Hanne M Møllergård, John C Morris, Barbara Mroczko, Stefan Van der Mussele, Duk L Na, Andrew Newberg, Agneta Nordberg, Arto Nordlund, Gerald P Novak, George P Paraskevas, Lucilla Parnetti, Gayan Perera, Oliver Peters, Julius Popp, Sudesh Prabhakar, Gil D Rabinovici, Inez H G B Ramakers, Lorena Rami, Catarina Resende de Oliveira, Juha O Rinne, Karen M Rodrigue, Eloy Rodríguez-Rodríguez, Catherine M Roe, Uros Rot, Christopher C Rowe, Eckart Rüther, Osama Sabri, Páscual Sanchez-Juan, Isabel Santana, Marie Sarazin, Johannes Schröder, Christin Schütte, Sang W Seo, Femke Soetewey, Hilkka Soininen, Luiza Spiru, Hanne Struyfs, Charlotte E Teunissen, Magda Tsolaki, Rik Vandenberghe, Marcel M Verbeek, Victor L Villemagne, Stephanie J B Vos, Linda J C van Waalwijk van Doorn, Gunhild Waldemar, Anders Wallin, Åsa K Wallin, Jens Wiltfang, David A Wolk, Marzena Zboch, Henrik Zetterberg, Willemijn J Jansen, Rik Ossenkoppele, Dirk L Knol, Betty M Tijms, Philip Scheltens, Frans R J Verhey, Pieter Jelle Visser, Amyloid Biomarker Study Group, Pauline Aalten, Dag Aarsland, Daniel Alcolea, Myriam Alexander, Ina S Almdahl, Steven E Arnold, Inês Baldeiras, Henryk Barthel, Bart N M van Berckel, Kristen Bibeau, Kaj Blennow, David J Brooks, Mark A van Buchem, Vincent Camus, Enrica Cavedo, Kewei Chen, Gael Chetelat, Ann D Cohen, Alexander Drzezga, Sebastiaan Engelborghs, Anne M Fagan, Tormod Fladby, Adam S Fleisher, Wiesje M van der Flier, Lisa Ford, Stefan Förster, Juan Fortea, Nadia Foskett, Kristian S Frederiksen, Yvonne Freund-Levi, Giovanni B Frisoni, Lutz Froelich, Tomasz Gabryelewicz, Kiran Dip Gill, Olymbia Gkatzima, Estrella Gómez-Tortosa, Mark Forrest Gordon, Timo Grimmer, Harald Hampel, Lucrezia Hausner, Sabine Hellwig, Sanna-Kaisa Herukka, Helmut Hildebrandt, Lianna Ishihara, Adrian Ivanoiu, William J Jagust, Peter Johannsen, Ramesh Kandimalla, Elisabeth Kapaki, Aleksandra Klimkowicz-Mrowiec, William E Klunk, Sebastian Köhler, Norman Koglin, Johannes Kornhuber, Milica G Kramberger, Koen Van Laere, Susan M Landau, Dong Young Lee, Mony de Leon, Viviana Lisetti, Alberto Lleó, Karine Madsen, Wolfgang Maier, Jan Marcusson, Niklas Mattsson, Alexandre de Mendonça, Olga Meulenbroek, Philipp T Meyer, Mark A Mintun, Vincent Mok, José Luis Molinuevo, Hanne M Møllergård, John C Morris, Barbara Mroczko, Stefan Van der Mussele, Duk L Na, Andrew Newberg, Agneta Nordberg, Arto Nordlund, Gerald P Novak, George P Paraskevas, Lucilla Parnetti, Gayan Perera, Oliver Peters, Julius Popp, Sudesh Prabhakar, Gil D Rabinovici, Inez H G B Ramakers, Lorena Rami, Catarina Resende de Oliveira, Juha O Rinne, Karen M Rodrigue, Eloy Rodríguez-Rodríguez, Catherine M Roe, Uros Rot, Christopher C Rowe, Eckart Rüther, Osama Sabri, Páscual Sanchez-Juan, Isabel Santana, Marie Sarazin, Johannes Schröder, Christin Schütte, Sang W Seo, Femke Soetewey, Hilkka Soininen, Luiza Spiru, Hanne Struyfs, Charlotte E Teunissen, Magda Tsolaki, Rik Vandenberghe, Marcel M Verbeek, Victor L Villemagne, Stephanie J B Vos, Linda J C van Waalwijk van Doorn, Gunhild Waldemar, Anders Wallin, Åsa K Wallin, Jens Wiltfang, David A Wolk, Marzena Zboch, Henrik Zetterberg
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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Source: PubMed