@article{3110064,
    title = "Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis",
    author = "Jansen, W.J. and Ossenkoppele, R. and Knol, D.L. and Tijms, B.M. and Scheltens, P. and Verhey, F.R.J. and Visser, P.J. and Aalten, P. and Aarsland, D. and Alcolea, D. and Alexander, M. and Almdahl, I.S. and Arnold, S.E. and Baldeiras, I. and Barthel, H. and Van Berckel, B.N.M. and Bibeau, K. and Blennow, K. and Brooks, D.J. and Van Buchem, M.A. and Camus, V. and Cavedo, E. and Chen, K. and Chetelat, G. and Cohen, A.D. and Drzezga, A. and Engelborghs, S. and Fagan, A.M. and Fladby, T. and Fleisher, A.S. and Van Der Flier, W.M. and Ford, L. and Forster, S. and Fortea, J. and Foskett, N. and Frederiksen, K.S. and Freund-Levi, Y. and Frisoni, G.B. and Froelich, L. and Gabryelewicz, T. and Gill, K.D. and Gkatzima, O. and Gomez-Tortosa, E. and Gordon, M.F. and Grimmer, T. and Hampel, H. and Hausner, L. and Hellwig, S. and Herukka, S.-K. and Hildebrandt, H. and Ishihara, L. and Ivanoiu, A. and Jagust, W.J. and Johannsen, P. and Kandimalla, R. and Kapaki, E. and Klimkowicz-Mrowiec, A. and Klunk, W.E. and Kohler, S. and Koglin, N. and Kornhuber, J. and Kramberger, M.G. and Van Laere, K. and Landau, S.M. and Lee, D.Y. and De Leon, M. and Lisetti, V. and Lleo, A. and Madsen, K. and Maier, W. and Marcusson, J. and Mattsson, N. and De Mendonca, A. and Meulenbroek, O. and Meyer, P.T. and Mintun, M.A. and Mok, V. and Molinuevo, J.L. and Mollergard, H.M. and Morris, J.C. and Mroczko, B. and Van Der Mussele, S. and Na, D.L. and Newberg, A. and Nordberg, A. and Nordlund, A. and Novak, G.P. and Paraskevas, G.P. and Parnetti, L. and Perera, G. and Peters, O. and Popp, J. and Prabhakar, S. and Rabinovici, G.D. and Ramakers, I.H.G.B. and Rami, L. and De Oliveira, C.R. and Rinne, J.O. and Rodrigue, K.M. and Rodriguez-Rodriguez, E. and Roe, C.M. and Rot, U. and Rowe, C.C. and Ruther, E. and Sabri, O. and Sanchez-Juan, P. and Santana, I. and Sarazin, M. and Schroder, J. and Schutte, C. and Seo, S.W. and Soetewey, F. and Soininen, H. and Spiru, L. and Struyfs, H. and Teunissen, C.E. and Tsolaki, M. and Vandenberghe, R. and Verbeek, M.M. and Villemagne, V.L. and Vos, S.J.B. and Van Waalwijk Van Doorn, L.J.C. and Waldemar, G. and Wallin, A. and Wallin, A.K. and Wiltfang, J. and Wolk, D.A. and Zboch, M. and Zetterberg, H. and the Amyloid Biomarker Study Group",
    journal = "JAMA - JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION - INTERNATIONAL EDITION",
    year = "2015",
    volume = "313",
    number = "19",
    pages = "1924-1938",
    publisher = "American Medical Association",
    issn = "0098-7484",
    doi = "10.1001/jama.2015.4668",
    keywords = "amyloid beta protein;  apolipoprotein E2;  apolipoprotein E3;  apolipoprotein E4;  biological marker;  amyloid beta protein;  apolipoprotein E4;  biological marker, age;  Alzheimer disease;  Article;  cognition;  cognitive defect;  dementia;  educational status;  gender;  genotype;  human;  medical record review;  mild cognitive impairment;  positron emission tomography;  prevalence;  priority journal;  risk factor;  systematic review;  vascular amyloidosis;  adult;  aged;  brain;  cerebrospinal fluid;  chemistry;  dementia;  female;  genetics;  male;  meta analysis;  middle aged;  pathology;  very elderly, Adult;  Age Factors;  Aged;  Aged, 80 and over;  Amyloid beta-Peptides;  Apolipoprotein E4;  Biological Markers;  Brain;  Cerebrospinal Fluid;  Dementia;  Female;  Genotype;  Humans;  Male;  Middle Aged;  Mild Cognitive Impairment;  Positron-Emission Tomography;  Prevalence;  Risk Factors",
    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. Copyright 2015 American Medical Association. All rights reserved."
}