Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysisShow others and affiliations
Number of Authors: 1292015 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 313, no 19, p. 1924-1938Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
American Medical Association , 2015. Vol. 313, no 19, p. 1924-1938
National Category
Medical and Health Sciences Gerontology, specialising in Medical and Health Sciences
Identifiers
URN: urn:nbn:se:oru:diva-79255DOI: 10.1001/jama.2015.4668ISI: 000354691200014PubMedID: 25988462Scopus ID: 2-s2.0-84937529452OAI: oai:DiVA.org:oru-79255DiVA, id: diva2:1386915
Note
Funding Agencies:
GE Healthcare, Appeared in article as GE Healthcare
Piramal
Merck & Company, Appeared in article as Merck
EU/EFPIA Innovative Medicines Initiative Joint Undertaking
EU Joint Programme-Neurodegenerative Disease Research (JPND)
Netherlands Organization for Health Research and Development, Appeared in article as ZonMw
Bristol-Myers Squibb, Appeared in article as Bristol-Myers Squibb
AstraZeneca, Appeared in article as Astra-Zeneca
H. Lundbeck
Novartis Pharmaceuticals
GE Healthcare, Appeared in article as GE Health
Siemens Healthcare
Roche Diagnostics
IBL International
Novartis, Appeared in article as Novartis
Eli Lilly, Appeared in article as Eli Lilly
French Ministry of Health
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA, Appeared in article as National Institutes of Health (NIH)
AVID/Lilly
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA, Appeared in article as NIH
Fred Simmons
Olga Mohan, and Charles and Joanne Knight Alzheimer's Research Initiative of the Washington University Knight Alzheimer's Disease Research Center
Roche Holding, Appeared in article as Roche
Abbott Laboratories, Appeared in article as AbbVie
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute on Aging (NIA), Appeared in article as NIA
Avid Radiopharmaceutical
Boehringer Ingelheim, Appeared in article as Boehringer Ingelheim
Piramal Imaging
Bayer AG, Appeared in article as Bayer
GE
Eli Lilly, Appeared in article as Lilly
Lundbeck Corporation, Appeared in article as Lundbeck
Elan
AstraZeneca, Appeared in article as AstraZeneca
Pfizer, Appeared in article as Pfizer
Taurx
Wyeth, Appeared in article as Wyeth
Baxter
Avid
Alzheimer's Association, Appeared in article as Alzheimer's Association
Indian Council of Medical Research, Appeared in article as Indian Council of Medical Research, New Delhi, India
Boehringer Ingelheim, Appeared in article as Boehringer Ingelheim Pharmaceuticals
Boehringer Ingelheim, Appeared in article as Boehringer-Ingelheim
Eisai Inc, Appeared in article as Eisai
Sanofi-Aventis, Appeared in article as sanofi-aventis
Roche Pharmaceuticals and Diagnostics
GlaxoSmithKline, Appeared in article as GlaxoSmithKline Biologicals
Jung-Diagnostics
Cytox
Medical Faculty, University of Freiburg
Banner Alzheimer Institute/Genentech
Synarc/Bioclinica
Indian Council of Medical Research, Appeared in article as Indian Council of Medical Research, India
European Union (European Regional Development Fund [ERDF])
Greek national funds through the Operational Program "Competitiveness and Entrepreneurship"
University of Pittsburgh, Appeared in article as University of Pittsburgh
Bayer Healthcare/Piramal Imaging (Berlin, Germany)
University of Antwerp Research Fund
Alzheimer Research Foundation (SAO-FRA)
FWO, Appeared in article as Research Foundation Flanders (FWO)
Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT), Appeared in article as Agency for Innovation by Science and Technology (IWT)
Belgian Science Policy Office Interuniversity Attraction Poles (IAP) program
Flemish Government-initiated Methusalem excellence grant
2020-01-202020-01-202023-08-16Bibliographically approved