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

Research output: Contribution to journalReview article

121 Citations (Scopus)

Abstract

Background: Preclinical 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. Objective: To 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. Design: We 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 (Aβ40, Aβ42, or Aβ42:Aβ40 ratio) and reporting an effect estimate for dementia, AD, or cognitive change. Main Outcome Measures: Using a standardized extraction form, appropriate study parameters on subject information, exposure, and outcomewere 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. Results: Thirteen studies with a total of 10 303 subjects met inclusion criteria for meta-analysis. Lower Aβ42: Aβ40 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 Aβ40 and Aβ42 alone were not significantly associated with either outcome. Conclusions: Overall, the literature indicates that plasma Aβ42:Aβ40 ratios predict development of AD and dementia. However, significant heterogeneity in the metaanalysis underlines the need for substantial further investigation of plasma amyloid-β levels as a preclinical biomarker.

Original languageEnglish (US)
Pages (from-to)824-831
Number of pages8
JournalArchives of Neurology
Volume69
Issue number7
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

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Amyloid
Dementia
Meta-Analysis
Alzheimer Disease
Odds Ratio
Biomarkers
Prospective Studies
Sex Distribution
Age Distribution
Cognitive Dysfunction
Systematic Review
Predictors
Plasma
Meta-analysis
MEDLINE
Sample Size
Publications
Outcome Assessment (Health Care)
Alzheimer's Disease
Databases

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

Plasma amyloid-β as a predictor of dementia and cognitive decline : A systematic review and meta-analysis. / Koyama, Alain; Okereke, Olivia I.; Yang, Ting; Blacker, Deborah; Selkoe, Dennis J.; Grodstein, Francine.

In: Archives of Neurology, Vol. 69, No. 7, 01.07.2012, p. 824-831.

Research output: Contribution to journalReview article

Koyama, Alain ; Okereke, Olivia I. ; Yang, Ting ; Blacker, Deborah ; Selkoe, Dennis J. ; Grodstein, Francine. / Plasma amyloid-β as a predictor of dementia and cognitive decline : A systematic review and meta-analysis. In: Archives of Neurology. 2012 ; Vol. 69, No. 7. pp. 824-831.
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AU - Selkoe, Dennis J.

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