Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI

Alzheimer Dis Assoc Disord. Apr-Jun 2015;29(2):101-9. doi: 10.1097/WAD.0000000000000071.

Abstract

Background: The 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 Aβ1-42 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 neurodegeneration, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Atrophy
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Clinical Trials as Topic
  • Cognition*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / psychology
  • Cohort Studies
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18
  • Hippocampus / pathology*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Outcome Assessment, Health Care
  • Peptide Fragments / cerebrospinal fluid
  • Positron-Emission Tomography
  • Radiopharmaceuticals

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • Radiopharmaceuticals
  • amyloid beta-protein (1-42)
  • Fluorodeoxyglucose F18