@article{ca78663fc068474988f49a016aaa8f14,
title = "Joint associations of β-amyloidosis and cortical thickness with cognition",
abstract = "In 1164 cognitively unimpaired persons, aged 50–95 years, from the population-based Mayo Clinic Study of Aging, we examined the relationships of baseline cognition and cognitive changes across the full range of cortical thickness of an Alzheimer signature region of interest and global β-amyloid levels measured by Pittsburgh compound B positron emission tomography (PIB PET) standardized uptake value ratio (SUVR). In machine-learning models accounting for both biomarkers simultaneously, worsening biomarker values were additive and associated with lower baseline global cognition and greater subsequent decline in global cognition. Associations between Alzheimer's disease signature cortical thickness or PIB PET β-amyloid SUVR and baseline cognition were mainly linear. Lower Alzheimer's disease signature cortical thickness values across the entire range of thickness predicted future decline in global cognitive scores, demonstrating its close relationship to cognitive functioning. PIB PET β-amyloid SUVR also predicted cognitive decline across its full range, even when cortical thickness was accounted for. PIB PET β-amyloid's relationship to cognitive decline was nonlinear, more prominent at lower β-amyloid levels and less prominent at higher β-amyloid levels.",
keywords = "Alzheimer's disease, Amyloid imaging, Cognitive aging, Neurodegeneration biomarkers, Structural MR imaging",
author = "Knopman, {David S.} and Lundt, {Emily S.} and Therneau, {Terry M.} and Prashanthi Vemuri and Lowe, {Val J.} and Kejal Kantarci and Gunter, {Jeffrey L.} and Senjem, {Matthew L.} and Mielke, {Michelle M.} and Machulda, {Mary M.} and Roberts, {Rosebud O.} and Boeve, {Bradley F.} and Jones, {David T.} and Petersen, {Ronald C.} and Jack, {Clifford R.}",
note = "Funding Information: This work was supported by NIH grants P50 AG16574, U01 AG06786, R01 AG034676, R01 AG41851, and R01 AG11378; the Elsie and Marvin Dekelboum Family Foundation; the Robert H. and Clarice Smith and Abigail Van Buren AD Research Program of the Mayo Foundation; GHR Foundation; Alexander Family AD Research Professorship of the Mayo Clinic; a Liston Award; Schuler Foundation; and the Mayo Foundation for Medical Education and Research. Funding Information: Dr. Knopman serves on a Data Safety Monitoring Board for the DIAN study and previously had served on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals; is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the AD Cooperative Study; and receives research support from the NIH. Dr. Jack serves on scientific advisory board for Eli Lilly & Company; receives research support from the NIH/NIA, and the Alexander Family AD Research Professorship of the Mayo Foundation; and holds stock in Johnson & Johnson. Ms. Lundt reports no disclosures. Dr. Vemuri receives research grants from the NIH/NIA. Dr. Mielke served as a consultant to Eli Lilly and Lysosomal Therapeutics, Inc. She receives research support from the National Institutes of Health (R01 AG49704, P50 AG44170, U01 AG06786, RF1 AG55151); Department of Defense (W81XWH-15-1); and unrestricted research grants from Biogen, Roche, and Lundbeck. Dr. Machulda receives research support from the NIH/NIA and NIDCD. Dr. Lowe serves on scientific advisory boards for Bayer Schering Pharma, Merck Research, Piramal Life Sciences and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). Dr. Kantarci receives research grants from the NIH/NIA. Dr. Gunter reports no disclosures. Mr. Senjem reports no disclosures. Dr. Jones reports no disclosures. Dr. Roberts reports no disclosures. She receives research grants from the NIH/NIA. Dr. Boeve has served as an investigator for clinical trials sponsored by GE Healthcare, FORUM Pharmaceuticals, C2N Diagnostics, and Axovant. He receives publishing royalties from Behavioral Neurology of Dementia (Cambridge Medicine, 2009, 2016). He serves on the Scientific Advisory Board of the Tau Consortium. He receives research support from the NIH, the Mayo Clinic Dorothy, Harry T. Mangurian Jr. Lewy Body Dementia Program, and the Little Family Foundation. Dr. Therneau receives research grants from the NIH. Dr. Petersen serves on data monitoring committees for Janssen Alzheimer Immunotherapy and is a consultant for Biogen, Roche, Merck, Genentech, Inc; receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH/NIA. ",
year = "2018",
month = may,
doi = "10.1016/j.neurobiolaging.2018.01.017",
language = "English (US)",
volume = "65",
pages = "121--131",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
}