Journal Article

DZNE-2020-07471

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.

Jansen, W. J. (Corresponding author) ; Ossenkoppele, R. ; Knol, D. L. ; Tijms, B. M. ; Scheltens, P. ; Verhey, F. R. J. ; Visser, P. J. ; Group, A. B. S. ; 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. ; van Buchem, M. A. ; Camus, V. ; Cavedo, E. ; Chen, K. ; Chetelat, G. ; Cohen, A. D. ; Drzezga, A. ; Engelborghs, S. ; Fagan, A. M. ; Fladby, T. ; Fleisher, A. S. ; van der Flier, W. M. ; Ford, L. ; Förster, S. ; Fortea, J. ; Foskett, N. ; Frederiksen, K. S. ; Freund-Levi, Y. ; Frisoni, G. B. ; Froelich, L. ; Gabryelewicz, T. ; Gill, K. D. ; Gkatzima, O. ; Gómez-Tortosa, E. ; Gordon, M. F. ; Grimmer, T. ; Hampel, H. ; Hausner, L. ; Hellwig, S. ; Herukka, S.-K. ; Hildebrandt, H. ; Ishihara, L. ; Ivanoiu, A. ; Jagust, W. J. ; Johannsen, P. ; Kandimalla, R. ; Kapaki, E. ; Klimkowicz-Mrowiec, A. ; Klunk, W. E. ; Köhler, S. ; Koglin, N. ; Kornhuber, J. ; Kramberger, M. G. ; Van Laere, K. ; Landau, S. M. ; Lee, D. Y. ; de Leon, M. ; Lisetti, V. ; Lleó, A. ; Madsen, K. ; Maier, W.DZNE* ; Marcusson, J. ; Mattsson, N. ; de Mendonça, A. ; Meulenbroek, O. ; Meyer, P. T. ; Mintun, M. A. ; Mok, V. ; Molinuevo, J. L. ; Møllergård, H. M. ; Morris, J. C. ; Mroczko, B. ; Van der Mussele, S. ; Na, D. L. ; Newberg, A. ; Nordberg, A. ; Nordlund, A. ; Novak, G. P. ; Paraskevas, G. P. ; Parnetti, L. ; Perera, G. ; Peters, O.DZNE* ; Popp, J. ; Prabhakar, S. ; Rabinovici, G. D. ; Ramakers, I. H. G. B. ; Rami, L. ; Resende de Oliveira, C. ; Rinne, J. O. ; Rodrigue, K. M. ; Rodríguez-Rodríguez, E. ; Roe, C. M. ; Rot, U. ; Rowe, C. C. ; Rüther, E. ; Sabri, O. ; Sanchez-Juan, P. ; Santana, I. ; Sarazin, M. ; Schröder, J. ; Schütte, C. ; Seo, S. W. ; Soetewey, F. ; Soininen, H. ; Spiru, L. ; Struyfs, H. ; Teunissen, C. E. ; Tsolaki, M. ; Vandenberghe, R. ; Verbeek, M. M. ; Villemagne, V. L. ; Vos, S. J. B. ; van Waalwijk van Doorn, L. J. C. ; Waldemar, G. ; Wallin, A. ; Wallin, Å. K. ; Wiltfang, J. ; Wolk, D. A. ; Zboch, M. ; Zetterberg, H.

2015
American Medical Association Chicago, Ill.

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Please use a persistent id in citations: doi:10.1001/jama.2015.4668

Abstract: 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.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).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.Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.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.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.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.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.

Keyword(s): Adult (MeSH) ; Age Factors (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Amyloid beta-Peptides: analysis (MeSH) ; Apolipoprotein E4: genetics (MeSH) ; Biomarkers: analysis (MeSH) ; Brain: pathology (MeSH) ; Cerebrospinal Fluid: chemistry (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Dementia: pathology (MeSH) ; Female (MeSH) ; Genotype (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Positron-Emission Tomography (MeSH) ; Prevalence (MeSH) ; Risk Factors (MeSH) ; Amyloid beta-Peptides ; Apolipoprotein E4 ; Biomarkers

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Contributing Institute(s):

1. U Clinical Researchers - Bonn (U Clinical Researchers - Bonn)
2. Clinical Study Team Berlin Priller (Clinical Study Team Berlin 1)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 40 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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