@article{908b40d882f74b2596ecc19d46cb069a,
title = "Evolution of neurodegeneration-imaging biomarkers from clinically normal to dementia in the Alzheimer disease spectrum",
abstract = "The availability of antemortem biomarkers for Alzheimer's disease (AD) enables monitoring the evolution of neurodegenerative processes in real time. Pittsburgh compound B (PIB) positron emission tomography (PET) was used to select participants in the Mayo Clinic Study of Aging and the Mayo Alzheimer's Disease Research Center with elevated β-amyloid, designated as “A+,” and hippocampal volume and 18fluorodeoxyglucose (FDG) positron emission tomography were used to characterize participants as having evidence of neurodegeneration (“N+”) at the baseline evaluation. There were 145 clinically normal (CN) A+ individuals, 62 persons with mild cognitive impairment (MCI) who were A+ and 20 with A+ AD dementia. Over a period of 1–6 years, MCI A+N+ individuals showed declines in medial temporal, lateral temporal, lateral parietal, and to a lesser extent, medial parietal regions for both FDG standardized uptake value ratio and gray matter volume that exceeded declines seen in the CN A+N+ group. The AD dementia group showed declines in the same regions on FDG standardized uptake value ratio and gray matter volume with rates that exceeded that in MCI A+N+. Expansion of regional involvement and faster rate of neurodegeneration characterizes progression in the AD pathway.",
keywords = "Alzheimer's disease, FDG PET imaging, Longitudinal study, MR imaging, PIB PET imaging",
author = "Knopman, {David S.} and Jack, {Clifford R.} and Lundt, {Emily S.} and Weigand, {Stephen D.} 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.}",
note = "Funding Information: David S. Knopman generated first draft and completed final draft. He also contributed for study concept and design; acquisition of data; analysis and interpretation; and critical revision of the article for important intellectual content. Clifford R. Jack contributed for analysis and interpretation; critical revision of the article for important intellectual content; and study supervision. Stephen D. Weigand contributed for analysis and interpretation and critical revision of the article for important intellectual content. Prashanthi Vemuri, Michelle M. Mielke, Mary M. Machulda, Val J. Lowe, Kejal Kantarci, Jeffrey L. Gunter, David T. Jones, and Rosebud O. Roberts contributed for critical revision of the article for important intellectual content. Matthew L. Senjem contributed for analysis, critical revision of the article for important intellectual content. Bradley F. Boeve contributed for acquisition of data; critical revision of the article for important intellectual content. Ronald C. Petersen contributed for acquisition of data; critical revision of the article for important intellectual content; and study supervision. This work was supported by NIH grants P50 AG16574 , U01 AG06786 , R01 AG41851 , and R01 AG11378 , the Elsie and Marvin Dekelboum Family Foundation and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation. David S. Knopman receives research support from the NIH. Prashanthi Vemuri receives research grants from the NIH/NIA. Michelle M. Mielke receives research grants from the NIH/NIA, Alzheimer Drug Discovery Foundation, Lewy Body Dementia Association, and the Michael J Fox Foundation. Kejal Kantarci receives research grants from the NIH/NIA. Rosebud O. Roberts receives research grants from the NIH/NIA. Appendix A Funding Information: David S. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals, and the Alzheimer's Disease Cooperative Study. Clifford R. Jack serves on scientific advisory board for Eli Lilly & Company; receives research support from the NIH/NIA, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation; and holds stock in Johnson & Johnson. Stephen D. Weigand reports no disclosures. Mary M. Machulda receives research support from the NIH/NIA and NIDCD. Val J. Lowe serves on scientific advisory boards for Bayer Schering Pharma, Piramal Life Sciences and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). Jeffrey L. Gunter, Matthew L. Senjem, David T. Jones, and Rosebud O. Roberts report no disclosures. Bradley F. Boeve receives royalties from the publication of Behavioral Neurology of Dementia and receives research support from Cephalon, Inc, Allon Therapeutics, GE Healthcare, the NIH/NIA, and the Mangurian Foundation. Ronald C. Petersen serves on data monitoring committees for Pfizer, Inc, Janssen Alzheimer Immunotherapy, and is a consultant for Biogen, Roche, Inc, Merck, Inc, and Genentech, Inc; receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003), and receives research support from the National Institute of Health. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = oct,
day = "1",
doi = "10.1016/j.neurobiolaging.2016.06.003",
language = "English (US)",
volume = "46",
pages = "32--42",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
}