@article{f679459fc5d7417e8f8461aae0f1255b,
title = "Relationships between β-amyloid and tau in an elderly population: An accelerated failure time model",
abstract = "Using positron emission tomography (PET)-derived amyloid and tau measurements from 1,495 participants, we explore the evolution of these values over time via an accelerated failure time (AFT) model. The AFT model assumes a shared pattern of progression, but one which is shifted earlier or later in time for each individual; an individual's time shift for amyloid and for tau are assumed to be linked. The resulting pattern for each outcome consists of an earlier indolent phase followed by sharp progression of the accumulation rate. APOE ε4 shifts the amyloid curve leftward (earlier) by 6.1 years, and the tau curve leftward by 2.6 years. Female sex shifts the amyloid curve leftward by 2.4 years and the tau curve leftward by 2.6 years. Per-person shifts (i.e., the individual's deviation from the population mean) for the onset of amyloid accumulation ranged from 13 years earlier to 13 years later (10th to 90th percentile) than average and 11 years earlier to 14 years later for tau, with an estimated correlation of 0.49. The average delay between amyloid increase and tau increase was 13.3 years.",
keywords = "Alzheimer's disease, Modeling, Progression",
author = "Therneau, {Terry M.} and Knopman, {David S.} and Lowe, {Val J.} and Hugo Botha and Jonathan Graff-Radford and Jones, {David T.} and Prashanthi Vemuri and Mielke, {Michelle M.} and Schwarz, {Christopher G.} and Senjem, {Matthew L.} and Gunter, {Jeffrey L.} and Petersen, {Ronald C.} and Jack, {Clifford R.}",
note = "Funding Information: This study was funded by the NIH (P50 AG16574, U01 AG06786, R37 AG011378, and R01 AG041851), the Elsie and Marvin Dekelboum Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the GHR Foundation, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. The data set analyzed for the current study is available from the investigators who can be contacted at mcsaadrcdatasharing@mayo.edu. The programs used to perform the analyses for the current study are available at https://github.com/therneau/AFTmodel. The directory also includes a more detailed comparison of this approach to the other methods. Drs. Therneau, Schwarz, Gunter, Graff-Radford, Botha, Jones, Vemuri, and Mielke report no disclosures. Mr. Senjem holds stock in Gilead Sciences, Inc. Inovio Pharmaceuticals, Medtronic, Oncothyreon, Inc. and PAREXEL International. Dr. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). Dr. Knopman served as Deputy Editor for Neurology?; served on a Data Safety Monitoring Board for Lilly Pharmaceuticals; serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; served as a consultant to TauRx Pharmaceuticals ending in November 2012; was an investigator in clinical trials sponsored by Baxter and Elan Pharmaceuticals in the past 2 years; is currently an investigator in a clinical trial sponsored by TauRx; and receives research support from the NIH (U01-HL096917, AG-037551). Dr. Petersen consults for Roche, Inc. Merck, Inc. Genentech, Inc. Biogen, Inc. and Eli Lilly and Company, Pfizer, Elan Pharmaceuticals, Wyeth Pharmaceuticals, and GE Healthcare, receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press, 2003), and receives research support from the NIH (UF1-AG32438, U19-AG24904, RF1-AG57547, U01-AG016976). Dr. Jack serves on an independent data monitoring board for Roche, has consulted for and served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Funding Information: Dr. Jack serves on an independent data monitoring board for Roche, has consulted for and served as a speaker for Eisai, and consulted for Biogen, but he receives no personal compensation from any commercial entity. He receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Funding Information: Dr. Petersen consults for Roche, Inc., Merck, Inc., Genentech, Inc., Biogen, Inc., and Eli Lilly and Company, Pfizer, Elan Pharmaceuticals, Wyeth Pharmaceuticals, and GE Healthcare, receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press, 2003), and receives research support from the NIH (UF1-AG32438, U19-AG24904, RF1-AG57547, U01-AG016976). Funding Information: Dr. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). Funding Information: This study was funded by the NIH (P50 AG16574, U01 AG06786, R37 AG011378, and R01 AG041851), the Elsie and Marvin Dekelboum Family Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program, the GHR Foundation, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = nov,
day = "15",
doi = "10.1016/j.neuroimage.2021.118440",
language = "English (US)",
volume = "242",
journal = "NeuroImage",
issn = "1053-8119",
publisher = "Academic Press Inc.",
}