TY - JOUR
T1 - White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration
AU - Alzheimer's Disease Neuroimaging Initiative
AU - Kandel, Benjamin M.
AU - Avants, Brian B.
AU - Gee, James C.
AU - McMillan, Corey T.
AU - Erus, Guray
AU - Doshi, Jimit
AU - Davatzikos, Christos
AU - Wolk, David A.
N1 - 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: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; 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.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. 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 Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Funding Information:
PPMI, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier, and UCB.
Funding Information:
Study funding: This research was supported by NIH grants T32-EB009384 , K01-ES025432-01 , R01-AG14971 , R01-NS061906 , AG010124 , AG043503 , AG040271 , and the Berkman Charitable Trust. Joint funding was provided by the Michael J. Fox Foundation for Parkinson's Research , Alzheimer's Association , and Weston Brain Institute ( BAND-9665 ). D.A.W. has performed consulting for GE Healthcare, Inc. B.M.K., B.B.A., J.C.G., C.T.M., J.M., C.D., and G.E. have no disclosures to report. The funding agencies had no say in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the article.
Publisher Copyright:
© 2016 The Authors.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2016
Y1 - 2016
N2 - Introduction: Cognitive tests and nonamyloid imaging biomarkers do not consistently identify preclinical AD. The objective of this study was to evaluate whether white matter hyperintensity (WMH) volume, a cerebrovascular disease marker, is more associated with preclinical AD than conventional AD biomarkers and cognitive tests. Methods: Elderly controls enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 158) underwent florbetapir-PET scans, psychometric testing, neuroimaging with MRI and PET, and APOE genetic testing. Elderly controls the Parkinson's progression markers initiative (PPMI, n = 58) had WMH volume, cerebrospinal fluid (CSF) Aβ1-42, and APOE status measured. Results: In the ADNI cohort, only WMH volume and APOE ε4 status were associated with cerebral Aβ (standardized β = 0.44 and 1.25, P = .03 and .002). The association between WMH volume and APOE ε4 status with cerebral Aβ (standardized β = 1.12 and 0.26, P = .048 and .045) was confirmed in the PPMI cohort. Discussion: WMH volume is more highly associated with preclinical AD than other AD biomarkers.
AB - Introduction: Cognitive tests and nonamyloid imaging biomarkers do not consistently identify preclinical AD. The objective of this study was to evaluate whether white matter hyperintensity (WMH) volume, a cerebrovascular disease marker, is more associated with preclinical AD than conventional AD biomarkers and cognitive tests. Methods: Elderly controls enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 158) underwent florbetapir-PET scans, psychometric testing, neuroimaging with MRI and PET, and APOE genetic testing. Elderly controls the Parkinson's progression markers initiative (PPMI, n = 58) had WMH volume, cerebrospinal fluid (CSF) Aβ1-42, and APOE status measured. Results: In the ADNI cohort, only WMH volume and APOE ε4 status were associated with cerebral Aβ (standardized β = 0.44 and 1.25, P = .03 and .002). The association between WMH volume and APOE ε4 status with cerebral Aβ (standardized β = 1.12 and 0.26, P = .048 and .045) was confirmed in the PPMI cohort. Discussion: WMH volume is more highly associated with preclinical AD than other AD biomarkers.
KW - Aging
KW - Alzheimer's disease
KW - Amyloid
KW - Leukoaraiosis
KW - MRI
KW - PET
KW - Preclinical Alzheimer's disease
KW - White matter
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U2 - 10.1016/j.dadm.2016.03.001
DO - 10.1016/j.dadm.2016.03.001
M3 - Article
C2 - 27489875
AN - SCOPUS:84966292139
VL - 4
SP - 18
EP - 27
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
SN - 2352-8729
ER -