TY - JOUR
T1 - Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition
AU - Alzheimer's Disease Neuroimaging Initiative
AU - Toledo, Jon B.
AU - Weiner, Michael W.
AU - Wolk, David A.
AU - Da, Xiao
AU - Chen, Kewei
AU - Arnold, Steven E.
AU - Jagust, William
AU - Jack, Clifford
AU - Reiman, Eric M.
AU - Davatzikos, Christos
AU - Shaw, Leslie M.
AU - Trojanowski, John Q.
N1 - Funding Information:
Dr. Weiner reports stock/stock options from Elan, Synarc, travel expenses from Novartis, Tohoku University, Fundacio Ace, Travel eDreams, MCI Group, NSAS, Danone Trading, ANT Congress, NeuroVigil, CHRU-Hopital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, University of California, San Diego–ADNI, Paris University, Institut Catala de Neurociencies Aplicades, University of New Mexico School of Medicine, Ipsen, Clinical Trials on Alzheimer’s Disease, Pfizer, AD PD meeting, Paul Sabatier University, board membership for Lilly, Araclon, Institut Catala de Neurociencies Aplicades, Gulf War Veterans Illnesses Advisory Committee, VACO, Biogen Idec, Pfizer, consultancy from AstraZeneca, Araclon, Medivation/Pfizer, Ipsen, TauRx Therapeutics, Bayer Healthcare, Biogen Idec, ExonHit Therapeutics, Servier, Synarc, Pfizer, Janssen, honoraria from NeuroVigil, Insitut Catala de Neurociencies Aplicades, PMDA/Japanese Ministry of Health, Labour, and Welfare, Tohoku University, commercial research support from Merck, Avid; government research support, DOD, VA, outside the submitted work. Dr. Shaw serves as consultant for Janssen AI R & D Janssen AI R & D and Lilly, outside the submitted work. Dr. Jagust has served as consultant for Genentech, Synarc, Siemens, F. Hoffman La Roche, Tau Rx, and Janssen Alzheimer Immunotherapy, outside the submitted work. Dr. Arnold reports grants from NIH, the American Health Assistance Foundation and the Marian S Ware Alzheimer’s Program, several pharmaceutical companies, other from Universities, pharmaceutical companies and advisory/ speaking honoraria from Universities, pharmaceutical companies and law firms. Dr. Jack, Reiman, Chen, Wolk, Davatzikos, Da and Toledo have nothing to disclose.
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; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to Rev October 14, 2013 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 California, Los Angeles. JQT is the William Maul Measey-Truman G. Schnabel, Jr., Professor of Geriatric Medicine and Gerontology.
Publisher Copyright:
© 2014 Toledo et al.; licensee BioMed Central Ltd.
PY - 2014/1/27
Y1 - 2014/1/27
N2 - Introduction: Based on previous studies, a preclinical classification for Alzheimer's disease (AD) has been proposed. However, 1) specificity of the different neuronal injury (NI) biomarkers has not been studied, 2) subjects with subtle cognitive impairment but normal NI biomarkers (SCINIB) have not been included in the analyses and 3) progression to mild cognitive impairment (MCI) or dementia of the AD type (DAT), referred to here as MCI/DAT, varies between studies. Therefore, we analyzed data from 486 cognitively normal (CN) and 327 DAT subjects in the AD Neuroimaging Initiative (ADNI)-1/GO/2 cohorts. Results: In the ADNI-1 cohort (median follow-up of 6 years), 6.3% and 17.0% of the CN subjects developed MCI/DAT after 3 and 5 years follow-up, respectively. NI biomarker cutoffs [structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and cerebrospinal fluid (CSF) tau] were established in DAT patients and memory composite scores were calculated in CN subjects in a cross-sectional sample (n = 160). In the complete longitudinally followed CN ADNI cohort (n = 326, median follow-up of 2 years), CSF and MRI values predicted an increased conversion to MCI/DAT. Different NI biomarkers showed important disagreements for classifying subjects as abnormal NI [kappa = (-0.05)-(0.33)] and into AD preclinical groups. SCINIB subjects (5.0%) were more prevalent than AD preclinical stage 3 subjects (3.4%) and showed a trend for increased progression to MCI/DAT. Conclusions: Different NI biomarkers lead to different classifications of ADNI subjects, while structural MRI and CSF tau measures showed the strongest predictive value for progression to MCI/DAT. The newly defined SCINIB category of ADNI subjects is more prevalent than AD preclinical stage individuals.
AB - Introduction: Based on previous studies, a preclinical classification for Alzheimer's disease (AD) has been proposed. However, 1) specificity of the different neuronal injury (NI) biomarkers has not been studied, 2) subjects with subtle cognitive impairment but normal NI biomarkers (SCINIB) have not been included in the analyses and 3) progression to mild cognitive impairment (MCI) or dementia of the AD type (DAT), referred to here as MCI/DAT, varies between studies. Therefore, we analyzed data from 486 cognitively normal (CN) and 327 DAT subjects in the AD Neuroimaging Initiative (ADNI)-1/GO/2 cohorts. Results: In the ADNI-1 cohort (median follow-up of 6 years), 6.3% and 17.0% of the CN subjects developed MCI/DAT after 3 and 5 years follow-up, respectively. NI biomarker cutoffs [structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and cerebrospinal fluid (CSF) tau] were established in DAT patients and memory composite scores were calculated in CN subjects in a cross-sectional sample (n = 160). In the complete longitudinally followed CN ADNI cohort (n = 326, median follow-up of 2 years), CSF and MRI values predicted an increased conversion to MCI/DAT. Different NI biomarkers showed important disagreements for classifying subjects as abnormal NI [kappa = (-0.05)-(0.33)] and into AD preclinical groups. SCINIB subjects (5.0%) were more prevalent than AD preclinical stage 3 subjects (3.4%) and showed a trend for increased progression to MCI/DAT. Conclusions: Different NI biomarkers lead to different classifications of ADNI subjects, while structural MRI and CSF tau measures showed the strongest predictive value for progression to MCI/DAT. The newly defined SCINIB category of ADNI subjects is more prevalent than AD preclinical stage individuals.
KW - Alzheimer's disease
KW - Amyloid beta
KW - Cerebrospinal fluid
KW - Dementia
KW - Magnetic resonance imaging
KW - Tau
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U2 - 10.1186/2051-5960-2-26
DO - 10.1186/2051-5960-2-26
M3 - Review article
C2 - 24602322
AN - SCOPUS:84912086947
VL - 2
JO - Acta neuropathologica communications
JF - Acta neuropathologica communications
SN - 2051-5960
IS - 1
M1 - 26
ER -