title: Plasma amyloid-β as a predictor of dementia and cognitive decline: a systematic review and meta-analysis.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, University of California at San Francisco, USA. alain.koyama@va.gov
authors.forename: Alain
authors.initials: A
authors.lastname: Koyama
authors.forename: Olivia I
authors.initials: OI
authors.lastname: Okereke
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: Francine
authors.initials: F
authors.lastname: Grodstein
mesh_terms: D000544:Alzheimer Disease / Q000097:blood; D016229:Amyloid beta-Peptides / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood* / Q000175:diagnosis; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D003704:Dementia / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D011237:Predictive Value of Tests
chemical_list: D016229:Amyloid beta-Peptides