PT  - JOURNAL ARTICLE
AU  - Kewei Chen
AU  - Auttawut Roontiva
AU  - Pradeep Thiyyagura
AU  - Wendy Lee
AU  - Xiaofen Liu
AU  - Napatkamon Ayutyanont
AU  - Hillary Protas
AU  - Ji.Luo Luo
AU  - Robert Bauer
AU  - Cole Reschke
AU  - Daniel Bandy
AU  - Robert A. Koeppe
AU  - Adam S. Fleisher
AU  - Richard J. Caselli
AU  - Susan Landau
AU  - William J. Jagust
AU  - Michael W. Weiner
AU  - Eric M. Reiman
TI  - Improved Power for Characterizing Longitudinal Amyloid-β PET Changes and Evaluating Amyloid-Modifying Treatments with a Cerebral White Matter Reference Region
AID  - 10.2967/jnumed.114.149732
DP  - 2015 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 560--566
VI  - 56
IP  - 4
4099  - http://jnm.snmjournals.org/content/56/4/560.short
4100  - http://jnm.snmjournals.org/content/56/4/560.full
SO  - J Nucl Med2015 Apr 01; 56
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.