Biomarkers as Predictors for Conversion from Mild Cognitive Impairment to Alzheimer-Type Dementia: Implications for Trial Design

Ineke A. van Rossum, Stephanie Vos, Ron Handels, Pieter Jelle Visser*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

80 Citations (Web of Science)
39 Downloads (Pure)

Abstract

Disease modifying drugs for Alzheimer's disease (AD) are likely to be most effective when given in non-demented subjects. In this review we summarized biomarkers in cerebrospinal fluid (CSF) and blood that can predict AD-type dementia in subjects with mild cognitive impairment (MCI). In addition, we investigated whether these markers could reduce sample size and costs if used to select subjects for trials on the prevention of AD in subjects with MCI. A meta-analysis of markers that had been investigated in multiple studies showed that the combination of amyloid-beta (A beta)(1-42) and tau in CSF had the best predictive accuracy for AD (odds ratio (OR) 18.1, 95% confidence interval (CI) 9.6-32.4). A beta(1-42), total tau, and phosphorylated tau in CSF also predicted conversion, but with lower accuracy (OR 7.5 to 8.1). Plasma levels of A beta(1-40), A beta(1-42), the ratio A beta(1-42)/A beta(1-40) and homocysteine did not predict outcome. In a fictive trial design, the use of the combination of A beta(1-42) and tau in CSF in the selection of subjects could reduce sample size by 67% and trial costs by 60% compared to a trial in which unselected subjects with MCI would be enrolled. In conclusion, the combination of A beta(1-42) and tau in CSF is useful to select subjects for trials that aim to slow down the progression from MCI to AD-type dementia.
Original languageEnglish
Pages (from-to)881-891
JournalJournal of Alzheimer's Disease
Volume20
Issue number3
DOIs
Publication statusPublished - 2010

Keywords

  • Alzheimer's disease
  • biomarkers
  • blood
  • cerebrospinal fluid
  • cost-benefit
  • decision analysis
  • mild cognitive impairment

Cite this