Abstract
Amyloid-β (Aβ) deposition as seen on positron emission tomography (PET) using an Aβ binding agent is a critical diagnostic biomarker for Alzheimer’s disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or in cognitively unimpaired (CU) has been widely reported and is poorly understood. Methods: To investigate the suitability of WM as a reference region and the factors affecting WM 11C-Pittsburgh Compound B (PiB) uptake variability, we conducted a retrospective study on two large data sets: 1) a longitudinal study of participants (n = 577) who were CU, had mild cognitive impairment (MCI), or had dementia likely due to AD (ADD); and 2) a cross-sectional study of single-scan PET imaging in CU subjects (n = 1349). In the longitudinal study, annual changes in WM PiB uptake were assessed, and in the cross-sectional study, WM PiB uptake was assessed relative to subject age. Results: Overall, we found that WM PiB uptake showed age-related increases which varied with the WM regions selected. Further, variable annual WM PiB uptake changes were seen with different GM PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM PiB. These correlations should be considered when using WM for normalization in PiB PET studies. The cerebellar crus1+crus2 showed no increase with age and cerebellar GM+WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM PiB uptake may relate to disease progression, warranting examination of the causes of WM PiB uptake.
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.