Edinburgh Research Explorer

Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI

Research output: Contribution to journalArticle

  • Anna Caroli
  • Annapaola Prestia
  • Sara Wade
  • Kewei Chen
  • Napatkamon Ayutyanont
  • Susan M. Landau
  • Cindee Madison
  • Cathleen Haense
  • Karl Herholz
  • Eric M. Reiman
  • William J. Jagust
  • Giovanni B. Frisoni

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalAlzheimer disease and associated disorders
Issue number2
Early online dateDec 2014
Publication statusPublished - 1 Apr 2015


Background: Aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI).

Methods: Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer’s Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer’s Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Ab1-42 concentration—ABETA +) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy—HIPPO +). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms.

Results: Seventy-four ABETA + and 51 HIPPO + MCI patients were included in the study. Imaging biomarkers of neuro-degeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency.

Conclusion: These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.

ID: 80253714