Evidence map›Paper›PMID 22451159›Full record

SynthesisArchives of neurology2012

Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review and meta-analysis.

Alain Koyama, Olivia I Okereke, Ting Yang, Deborah Blacker, Dennis J Selkoe, Francine Grodstein

Open access · greenAbstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Archives of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 7 pooled it
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

116 citing papers in PubMed, 7 syntheses or guidelines pooled it, 224 citations in OpenAlex.

  1. Pooled it
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  6. Plasma amyloid-β and risk of Alzheimer's disease in the Framingham Heart Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015
    Pooled it
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  8. Trial
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  16. Epigenetic clocks and longitudinal plasma biomarkers of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  17. Article
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  19. Alzheimer's disease plasma biomarkers in the Midwestern Amish.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  20. Modeling the ratio of correlated biomarkers using copula regression.Statistical methods in medical research · 2025
    Article

56 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Alain KoyamaDepartment of Psychiatry, University of California at San Francisco, USA. alain.koyama@va.gov
Olivia I Okereke
Ting Yang
Deborah Blacker
Dennis J Selkoe
Francine Grodstein
Harvard University · USBrigham and Women's Hospital · USMassachusetts General Hospital · USUniversity of California, San Francisco · US

Funding

Plasma Amyloid-Beta, Insulin, and Cognitive DeclineR01AG024215 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI GRODSTEIN, FRANCINE · 2004 to 2008
$2.5M
NIA NIH HHS AG24215NIA NIH HHS R01 AG024215
6 · The paper itself

Abstract

backgroundPreclinical prediction of Alzheimer disease (AD) is important and critical to effective intervention. Plasma levels of amyloid-β (Aβ) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data.

objectiveTo conduct a systematic review and meta-analysis of relevant prospective studies to determine whether plasma amyloid-β levels may predict development of dementia, AD, and cognitive decline.

designWe searched prospective studies published between 1995 and 2011 indexed in the MEDLINE, EMBASE, and PsycINFO databases. Selected studies included those measuring at least 1 relevant plasma amyloid-β species (Aβ(40), Aβ(42), or Aβ(42):Aβ(40) ratio) and reporting an effect estimate for dementia, AD, or cognitive change.

main outcome measuresUsing a standardized extraction form, appropriate study parameters on subject information, exposure, and outcome were extracted. Random effects models were used to generate summary risk ratios and 95% confidence intervals comparing the bottom vs top quantiles for each plasma measure.

resultsThirteen studies with a total of 10 303 subjects met inclusion criteria for meta-analysis. Lower Aβ(42):Aβ(40) ratios were significantly associated with development of AD (summary risk ratio, 1.60; 95% CI, 1.04-2.46; P = .03) and dementia (risk ratio, 1.67; 95% CI, 1.02-2.75; P = .04). Significant heterogeneity was found for both summary estimates, which could not be explained by participants' age, sex distribution, the study's follow-up time, or year of publication. Plasma levels of Aβ(40) and Aβ(42) alone were not significantly associated with either outcome.

conclusionsOverall, the literature indicates that plasma Aβ(42):Aβ(40) ratios predict development of AD and dementia. However, significant heterogeneity in the meta-analysis underlines the need for substantial further investigation of plasma amyloid-β levels as a preclinical biomarker.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCognition DisordersDatabases, BibliographicDementiaHumansPredictive Value of TestsAmyloid beta-Peptides

Identifiers

PMID22451159
PMCPMC3772635
OpenAlexW2046059051

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.