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Meta-Analysis
. 2012 Jul;69(7):824-31.
doi: 10.1001/archneurol.2011.1841.

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

Alain Koyama  1 , Olivia I Okereke, Ting Yang, Deborah Blacker, Dennis J Selkoe, Francine Grodstein
Affiliations
Meta-Analysis

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

Alain Koyama et al. Arch Neurol. 2012 Jul.

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 (Aβ(40), Aβ(42), or Aβ(42):Aβ(40) 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 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.

Results: Thirteen 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.

Conclusions: Overall, 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.

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Figures

Figure 1
Figure 1
Study Selection
Figure 2
Figure 2
Meta-Analysis of Plasma Aβ and Incident Dementia
Figure 3
Figure 3
Meta-Analysis of Plasma Aβ and Incident Alzheimer’s Disease
See this image and copyright information in PMC

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