Use of white matter reference regions for detection of change in florbetapir positron emission tomography from completed phase 3 solanezumab trials. Issue 10 (30th March 2017)

• Record Type: Journal Article
• Authors: Fleisher, Adam S.; Joshi, Abhinay D.; Sundell, Karen L.; Chen, Yun‐Fei; Kollack‐Walker, Sara; Lu, Ming; Chen, Sherry; Devous, Michael D.; Seibyl, John; Marek, Kenneth; Siemers, Eric R.; Mintun, Mark A.
• Is Part Of: Alzheimer's & dementia. Volume 13:Issue 10(2017)
• Page Start: 1117
• Page End: 1124
• Publication Date: 2017-03-30
• Subjects: Alzheimer's disease -- Serial PET imaging -- Reference region -- Solanezumab -- Growth mixture model -- Trajectory -- Disease course -- Florbetapir; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2017.02.009
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Introduction: We compared subject‐specific white matter (SSWM) and whole cerebellum (CBL) reference regions for power to detect longitudinal change in amyloid positron emission tomography signal. Methods: Positive florbetapir positron emission tomography scans were analyzed from participants (66 placebo treated and 63 solanezumab treated) with mild dementia caused by Alzheimer's disease from the EXPEDITION and EXPEDITION2 studies. For comparison to CBL, a second normalization was performed on longitudinal data using an SSWM correction factor (SSWM normalization ratio [SSWMnr]). Analysis of covariance assessed baseline to 18‐month change between treatment with solanezumab and placebo. Sample and effect size estimations provided magnitude of observed treatment changes. Results: Longitudinal percent change between placebo and solanezumab using CBL was not significant ( P = .536) but was significant for SSWMnr ( P = .042). Compared with CBL, SSWMnr technique increased the power to detect a treatment difference, more than tripling the effect size and reducing the sample size requirements by 85% to 90%. Discussion: Adjusting longitudinal standardized uptake value ratios with an SSWM reference region in these antiamyloid treatment trials increased mean change detection and decreased variance resulting in the substantial improvement in statistical power to detect change.