@article{927f1ac88d9146df94955343eec452a6,
title = "Investigation of white matter PiB uptake as a marker of white matter integrity",
abstract = "Objective: To investigate the associations of Pittsburgh compound-B (PiB) uptake in white matter hyperintensities (WMH) and normal appearing white matter (NAWM) with white matter (WM) integrity measured with DTI and cognitive function in cognitively unimpaired older adults. Methods: Cognitively unimpaired older adults from the population-based Mayo Clinic Study of Aging (n = 537, age 65–95) who underwent both PiB PET and DTI were included. The associations of WM PiB standard uptake value ratio (SUVr) with fractional anisotropy (FA) and mean diffusivity (MD) in the WMH and NAWM were tested after adjusting for age. The associations of PiB SUVr with cognitive function z-scores were tested after adjusting for age and global cortical PiB SUVr. Results: The WMH PiB SUVr was lower than NAWM PiB SUVr (P < 0.001). In the WMH, lower PiB SUVr correlated with lower FA (r = 0.21, P < 0.001), and higher MD (r = −0.31, P < 0.001). In the NAWM, lower PiB SUVr only correlated with higher MD (r = −0.10, P = 0.02). Both in the WMH and NAWM, lower PiB SUVr was associated with lower memory, language, and global cognitive function z-scores after adjusting for age and global cortical PiB SUVr. Interpretation: Reduced PiB uptake in the WMH is associated with a loss of WM integrity and cognitive function after accounting for the global cortical PiB uptake, suggesting that WM PiB uptake may be an early biomarker of WM integrity that precedes cognitive impairment in older adults. When using WM as a reference region in cross-sectional analysis of PiB SUVr, individual variability in WMH volume as well as age should be considered.",
author = "Burcu Zeydan and Schwarz, {Christopher G.} and Lowe, {Val J.} and Reid, {Robert I.} and Przybelski, {Scott A.} and Lesnick, {Timothy G.} and Kremers, {Walter K.} and Senjem, {Matthew L.} and Gunter, {Jeffrey L.} and Min, {Hoon Ki} and Prashanthi Vemuri and Knopman, {David S.} and Petersen, {Ronald C.} and Jack, {Clifford R.} and Kantarci, {Orhun H.} and Kejal Kantarci",
note = "Funding Information: B Zeydan has nothing to disclose. CG Schwarz receives funding from the NIH. VJ Lowe consults for Bayer Scher-ing Pharma, Piramal Life Sciences and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals and the NIH (NIA, NCI). RI Reid, SA Przybelski, TG Lesnick and WK Kremers have nothing to disclose. ML Senjem discloses equity/options ownership in medical companies: Gilead Sciences Inc., Inovio Pharmaceuticals, Medtronic, and PAREXEL International Corporation. JL Gunter has nothing to disclose. H Min has nothing to disclose. P Vemuri receives funding from the NIH (NIA and NINDS). DS Knopman serves on a Data Safety Monitoring Board for the DIAN study; is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals and the University of Southern California; and receives research support from the NIH. RC Petersen receives funding from the NIH, has served on the National Advisory Council on Aging and on the scientific advisory boards of Pfizer, GE Healthcare, Elan Pharmaceuticals, and Janssen Alzheimer Immunotherapy, has received publishing royalties from Oxford University Press, and has been a consultant for Roche Incorporated, Merck, Genentech, Biogen, and Eli Lily. CR Jack consults for Lily and serves on an independent data monitoring board for Roche but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Clinic. OH Kantarci receives grant support from Biogen Inc. K Kantarci serves on data safety monitoring board for Takeda Global Research and Development Center, Inc, receives research support from Avid Radiopharmaceuticals and Eli Lilly, and receives funding from the NIH and Alzheimer{\textquoteright}s Drug Discovery Foundation. Funding Information: This study was funded by the National Institutes of Health (NIH) [R01 AG040042, P50 AG016574, U01 AG006786, RF1 AG57547, C06 RR018898, R01 AG034676, R01 AG011378, R01 AG041851, R01 NS097495], the Elsie and Marvin Dekelboum Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer{\textquoteright}s Disease Research Program, the GHR Foundation, Mayo Foundation for Medical Education and Research, the Schuler Foundation and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Clinic. The funding sources had no role in study design, collection, analysis, interpretation, or decision to submit this paper.",
year = "2019",
month = apr,
doi = "10.1002/acn3.741",
language = "English (US)",
volume = "6",
pages = "678--688",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Inc.",
number = "4",
}