Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials: Effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size

Peng Yu, Jia Sun, Robin Wolz, Diane Stephenson, James Brewer, Nick C. Fox, Patricia E. Cole, Clifford R Jr. Jack, Derek L G Hill, Adam J. Schwarz

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The objective of this study was to evaluate the effect of computational algorithm, measurement variability, and cut point on hippocampal volume (HCV)-based patient selection for clinical trials in mild cognitive impairment (MCI). We used normal control and amnestic MCI subjects from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) as normative reference and screening cohorts. We evaluated the enrichment performance of 4 widely used hippocampal segmentation algorithms (FreeSurfer, Hippocampus Multi-Atlas Propagation and Segmentation (HMAPS), Learning Embeddings Atlas Propagation (LEAP), and NeuroQuant) in terms of 2-year changes in Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Sum of Boxes (CDR-SB). We modeled the implications for sample size, screen fail rates, and trial cost and duration. HCV based patient selection yielded reduced sample sizes (by ~40%-60%) and lower trial costs (by ~30%-40%) across a wide range of cut points. These results provide a guide to the choice of HCV cut point for amnestic MCI clinical trials, allowing an informed tradeoff between statistical and practical considerations.

Original languageEnglish (US)
Pages (from-to)808-818
Number of pages11
JournalNeurobiology of Aging
Volume35
Issue number4
DOIs
StatePublished - Apr 2014

Fingerprint

Sample Size
Atlases
Biomarkers
Costs and Cost Analysis
Patient Selection
Alzheimer Disease
Clinical Trials
Neuroimaging
Dementia
Hippocampus
Learning
Cognitive Dysfunction

Keywords

  • Biomarker
  • Clinical trials
  • Enrichment
  • Hippocampal volume
  • Hippocampus
  • Inclusion criterion
  • MRI
  • Structural MRI

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials : Effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size. / Yu, Peng; Sun, Jia; Wolz, Robin; Stephenson, Diane; Brewer, James; Fox, Nick C.; Cole, Patricia E.; Jack, Clifford R Jr.; Hill, Derek L G; Schwarz, Adam J.

In: Neurobiology of Aging, Vol. 35, No. 4, 04.2014, p. 808-818.

Research output: Contribution to journalArticle

Yu, Peng ; Sun, Jia ; Wolz, Robin ; Stephenson, Diane ; Brewer, James ; Fox, Nick C. ; Cole, Patricia E. ; Jack, Clifford R Jr. ; Hill, Derek L G ; Schwarz, Adam J. / Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials : Effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size. In: Neurobiology of Aging. 2014 ; Vol. 35, No. 4. pp. 808-818.
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