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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Neurology, Memory and Aging Center, University of California, San Francisco; Helen Wills Neuroscience Institute, University of California, Berkeley.
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
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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

Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved

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Freund-Levi, Yvonne

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