@article{b9a89d8e8f5e4a6baf4e1d70405d4ca6,
title = "Defining SNAP by cross-sectional and longitudinal definitions of neurodegeneration",
abstract = "Introduction: Suspected non-Alzheimer's pathophysiology (SNAP) is a biomarker driven designation that represents a heterogeneous group in terms of etiology and prognosis. SNAP has only been identified by cross-sectional neurodegeneration measures, whereas longitudinal measures might better reflect “active” neurodegeneration and might be more tightly linked to prognosis. We compare neurodegeneration defined by cross-sectional {\textquoteleft}hippocampal volume{\textquoteright} only (SNAP/L−) versus both cross-sectional and longitudinal {\textquoteleft}hippocampal atrophy rate{\textquoteright} (SNAP/L+) and investigate how these definitions impact prevalence and the clinical and biomarker profile of SNAP in Mild Cognitive Impairment (MCI). Methods: 276 MCI patients from ADNI-GO/2 were designated amyloid “positive” (A+) or “negative” (A−) based on their florbetapir scan and neurodegeneration {\textquoteleft}positive{\textquoteright} or {\textquoteleft}negative{\textquoteright} based on cross-sectional hippocampal volume and longitudinal hippocampal atrophy rate. Results: 74.1% of all SNAP participants defined by the cross-sectional definition of neurodegeneration also met the longitudinal definition of neurodegeneration, whereas 25.9% did not. SNAP/L+ displayed larger white matter hyperintensity volume, a higher conversion rate to dementia over 5 years and a steeper decline on cognitive tasks compared to SNAP/L− and the A- CN group. SNAP/L− had more abnormal values on neuroimaging markers and worse performance on cognitive tasks than the A- CN group, but did not show a difference in dementia conversion rate or longitudinal cognition. Discussion: Using a longitudinal definition of neurodegeneration in addition to a cross-sectional one identifies SNAP participants with significant cognitive decline and a worse clinical prognosis for which cerebrovascular disease may be an important driver.",
keywords = "Cross-sectional, Longitudinal, Mild cognitive impairment, Neurodegeneration, Suspected non-AD pathology",
author = "{for the} and {Alzheimer's Disease Neuroimaging Initiative} and Wisse, {L. E.M.} and Das, {S. R.} and C. Davatzikos and Dickerson, {B. C.} and Xie, {S. X.} and Yushkevich, {P. A.} and Wolk, {D. A.}",
note = "Funding Information: This work was supported by the National Institute on Aging grants: R01 AG037376 , P30 AG010124 , R01 AG054409 ; National Institute of Biomedical Imaging and Bioengineering grant: R01 EB017255 ; and the Berkman Charitable Trust . Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2018",
year = "2018",
doi = "10.1016/j.nicl.2018.02.008",
language = "English (US)",
volume = "18",
pages = "407--412",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",
}