@article{eecfc817c09f4c918690e9bd69805017,
title = "NIA-AA staging of preclinical Alzheimer disease: Discordance and concordance of CSF and imaging biomarkers",
abstract = "The National Institute of Aging and Alzheimer's Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of β-amyloid (CSF Aβ1-42 and positron emission tomography imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural magnetic resonance imaging) with longitudinal clinical follow-up. Participants were classified in preclinical AD stage 1 (β-amyloidosis) or preclinical AD stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer disease pathophysiology group (neuronal injury without β-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based on neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury and has important implications for clinical trials using biomarkers for enrollment or as surrogate end point measures.",
keywords = "Aging, Alzheimer's disease, Amyloid, Biomarkers, Cerebrospinal fluid, Comorbidities, Diagnosis, MRI, Neuroimaging, Neuronal injury, PET, Prognosis",
author = "Vos, {Stephanie J.B.} and Gordon, {Brian A.} and Yi Su and Visser, {Pieter Jelle} and Holtzman, {David M.} and Morris, {John C.} and Fagan, {Anne M.} and Benzinger, {Tammie L.S.}",
note = "Funding Information: The authors gratefully acknowledge the contributions of Nigel J. Cairns, and the Administrative, Biomarker, Clinical, Genetic, Imaging, Neuropathology, and Psychometric Cores of the Knight Alzheimer's Disease Research Center. Research reported in this publication was supported by NIH grant P01 AG026276 , P01 AG003991 , P50 AG005681 , and Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS). This work used the services of the Neuroimaging Informatics and Analysis Center, supported by NIH grant 5P30NS048056 . Generous support was provided by Fred Simmons and Olga Mohan, the Barnes-Jewish Hospital Foundation and by Charles F. and Joanne Knight Alzheimer's Research Initiative. The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Stephanie J.B. Vos reports a grant from ZonMw . Pieter Jelle Visser reports grants from EU/EFPIA Innovative Medicines Initiative Joint Undertaking , grants from EU Joint Programme – Neurodegenerative Disease Research (JPND) and ZonMw , during the conduct of the study; other from Roche Diagnostics , grants from Bristol-Myers Squibb , non-financial support from GE Healthcare, outside the submitted work. David M. Holtzman reports grants from the NIH , The JPB Foundation , Cure Alzheimer{\textquoteright}s Fund , Eli Lilly , AbbVie , and C2N Diagnostics . John C. Morris is funded by NIH grants #P50AG005681 ; P01AG003991 ; P01AG026276 and U19AG032438 . Tammie L.S. Benzinger reports grants from NIH and Avid Radiopharmaceuticals , participation in clinical trials by Avid Radiopharmaceuticals, Lilly, and Roche. Funding Information: Stephanie J.B. Vos receives research support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies{\textquoteright} in kind contribution. Pieter Jelle Visser receives research support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies{\textquoteright} in kind contribution. David M. Holtzman is co-founder of C2N Diagnostics and LLC, is on the scientific advisory boards of C2N Diagnostics, Genentech, Neurophage, AstraZeneca, and Denali and is consultant for Eli Lilly, Biogen, and AbbVie. John C. Morris has participated or is currently participating in clinical trials of antidementia drugs sponsored by the following companies: Janssen Immunotherapy, Pfizer, Eli Lilly/Avid Radiopharmaceuticals, SNIFF (The Study of Nasal Insulin to Fight Forgetfullness) study, and A4 (The Anti-Amyloid Treatment in Asymptomatic Alzheimer{\textquoteright}s Disease) trial. John C. Morris has served as a consultant for Lilly USA, ISIS Pharmaceuticals, and Charles Dana Foundation. He receives research support from Eli Lilly/Avid Radiopharmaceuticals. Anne M. Fagan is on the scientific advisory boards of IBL International and Roche and is a consultant for AbbVie, DiamiR and Novartis. Tammie L.S. Benzinger received payment for development of educational materials from Medscape and Quintiles. Brian A. Gordon and Yi Su report no conflicts of interest. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = aug,
day = "1",
doi = "10.1016/j.neurobiolaging.2016.03.025",
language = "English",
volume = "44",
pages = "1--8",
journal = "Neurobiology of Aging",
issn = "0197-4580",
}