RT Journal Article
SR Electronic
T1 Improved Power for Characterizing Longitudinal Amyloid-β PET Changes and Evaluating Amyloid-Modifying Treatments with a Cerebral White Matter Reference Region
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 560
OP 566
DO 10.2967/jnumed.114.149732
VO 56
IS 4
A1 Kewei Chen
A1 Auttawut Roontiva
A1 Pradeep Thiyyagura
A1 Wendy Lee
A1 Xiaofen Liu
A1 Napatkamon Ayutyanont
A1 Hillary Protas
A1 Ji.Luo Luo
A1 Robert Bauer
A1 Cole Reschke
A1 Daniel Bandy
A1 Robert A. Koeppe
A1 Adam S. Fleisher
A1 Richard J. Caselli
A1 Susan Landau
A1 William J. Jagust
A1 Michael W. Weiner
A1 Eric M. Reiman
YR 2015
UL http://jnm.snmjournals.org/content/56/4/560.abstract
AB 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 Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials.