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, Pauline Aalten, Dag Aarsland, Daniel Alcolea, Myriam Alexander, Ina S. Almdahl, Steven E. Arnold, Ines Baldeiras, Henryk Barthel, Bart N M Van Berckel, Kristen Bibeau, Kaj Blennow, David J. Brooks, Mark A. Van BuchemVincent 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 Forster, Juan Fortea, Nadia Foskett, Kristian S. Frederiksen, Yvonne Freund-Levi, Giovanni B. Frisoni, Lutz Froelich, Tomasz Gabryelewicz, Kiran Dip Gill, Olymbia Gkatzima, Estrella Gomez-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 Kohler, Norman Koglin, Johannes Kornhuber, Milica G. Kramberger, Koen Van Laere, Susan M. Landau, Dong Young Lee, Mony De Leon, Viviana Lisetti, Alberto Lleo, Karine Madsen, Wolfgang Maier, Jan Marcusson, Niklas Mattsson, Alexandre De Mendonca, Olga Meulenbroek, Philipp T. Meyer, Mark A. Mintun, Vincent Mok, Jose Luis Molinuevo, Hanne M. Mollergard, 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 Rodriguez-Rodriguez, Catherine M. Roe, Uros Rot, Christopher C. Rowe, Eckart Ruther, Osama Sabri, Pascual Sanchez-Juan, Isabel Santana, Marie Sarazin, Johannes Schroder, Christin Schutte, 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, Asa K. Wallin, Jens Wiltfang, David A. Wolk, Marzena Zboch, Henrik Zetterberg

Research output: Contribution to journalArticle

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 andWeb 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 recordswere 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.

Original languageEnglish
Pages (from-to)1924-1938
Number of pages15
JournalJAMA - Journal of the American Medical Association
Volume313
Issue number19
DOIs
Publication statusPublished - May 19 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Jansen, W. J., Ossenkoppele, R., Knol, D. L., Tijms, B. M., Scheltens, P., Verhey, F. R. J., Visser, P. J., Aalten, P., Aarsland, D., Alcolea, D., Alexander, M., Almdahl, I. S., Arnold, S. E., Baldeiras, I., Barthel, H., Van Berckel, B. N. M., Bibeau, K., Blennow, K., Brooks, D. J., ... Zetterberg, H. (2015). Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA - Journal of the American Medical Association, 313(19), 1924-1938. https://doi.org/10.1001/jama.2015.4668