Improved power for characterizing longitudinal amyloid-βPET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region

Kewei Chen, Auttawut Roontiva, Pradeep Thiyyagura, Wendy Lee, Xiaofen Liu, Napatkamon Ayutyanont, Hillary Protas, Ji Luo Luo, Robert Bauer, Cole Reschke, Daniel Bandy, Robert A. Koeppe, Adam S. Fleisher, Richard J. Caselli, Susan Landau, William J. Jagust, Michael W. Weiner, Eric M. Reiman

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments. Methods: Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines. Results: As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines. Conclusion: A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβincreases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials.

Original languageEnglish (US)
Pages (from-to)560-566
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • Alzheimer disease
  • Biomarkers
  • Clinical trial sample size
  • Florbetapir PET
  • Image analysis
  • Statistical power

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Improved power for characterizing longitudinal amyloid-βPET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region'. Together they form a unique fingerprint.

Cite this