Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 59, Issue 10, Pages 1583-1589Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.117.204271
Keywords
AD; C-11-PiB; white matter; amyloid-beta; PET
Funding
- NIH [P50 AG16574, U01 AG06786, R01 AG11378, R01 AG041851]
- Elsie and Marvin Dekelboum Family Foundation
- GHR Foundation
- Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation
- GE Healthcare
- Siemens Molecular Imaging
- AVID Radiopharmaceuticals
- Biogen
- Lilly Pharmaceuticals
- Alzheimer's Disease Cooperative Study
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Amyloid-beta (A beta) deposition as seen on PET using an A beta-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial A beta PET studies; however, nonspecific WM retention in A beta PET in people with dementia or 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 C-11-Pittsburgh compound B (C-11-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n 5 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a crosssectional study of single-scan PET imaging in CU subjects (n 5 1,349). In the longitudinal study, annual changes in WM C-11-PiB uptake were assessed, and in the cross-sectional study, WM C-11-PiB uptake was assessed relative to subject age. Results: Overall, we found that WM C-11-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM C-11-PiB uptake changes were seen with different gray matter (GM) C-11-PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM C-11-PiB. These correlations should be considered when using WM for normalization in C-11-PiB PET studies. The cerebellar crus(11)crus2 showed no increase with age and cerebellar GM1WM 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 C-11-PiB uptake may relate to disease progression, warranting examination of the causes of WM C-11-PiB uptake.
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