TY - JOUR
T1 - Longitudinal MRI atrophy biomarkers
T2 - Relationship to conversion in the ADNI cohort
AU - Risacher, Shannon L.
AU - Shen, Li
AU - West, John D.
AU - Kim, Sungeun
AU - McDonald, Brenna C.
AU - Beckett, Laurel A.
AU - Harvey, Danielle J.
AU - Jack, Clifford R.
AU - Weiner, Michael W.
AU - Saykin, Andrew J.
N1 - Funding Information:
Data analysis was supported in part by the following grants from the National Institutes of Health : NIA R01 AG19771 to AJS and P30 AG10133-18S1 to B. Ghetti and AJS, and NIBIB R03 EB008674 to LS; and by the Indiana Economic Development Corporation ( IEDC # 87884 to AJS).
Funding Information:
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health , Grants U01 AG024904 and RC2 AG036535 , PI: Michael W. Weiner, MD). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI 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. This research was also supported by NIH grants P30 AG010129 , K01 AG030514 , and the Dana Foundation . The National Cell Repository for Alzheimer's Disease ( NIH grant U24 AG021886 ) provided support for DNA and cell line banking and processing for ADNI.
Funding Information:
Drs. Risacher, Shen, Kim, West, McDonald, Beckett, and Harvey report no disclosures. Dr. Jack served on a scientific advisory board for Elan Corporation; receives research support from Pfizer Inc ., the Mayo U of MN Biotechnology Partnership, and holds stock in GE Healthcare. Dr. Weiner serves on scientific advisory boards for Bayer Schering Pharma, Eli Lilly and Company, CoMentis, Inc., Neurochem Inc, Eisai Inc., Avid Radiopharmaceuticals Inc., Aegis Therapies, Genentech, Inc., Allergan, Inc., Lippincott Williams & Wilkins, Bristol-Myers Squibb, Forest Laboratories, Inc., Pfizer Inc, McKinsey & Company, Mitsubishi, Tanabe Pharma Corporation, and Novartis; has received funding for travel from Nestle and Kenes International and to attend conferences not funded by industry; has received honoraria from the Rotman Research Institute and BOLT International; serves as a consultant for Elan Corporation; receives research support from Merck & Co. , Radiopharmaceuticals Inc., and holds stock in Synarc and Elan Corporation. Dr. Saykin receives support from the NIH ( R01 CA101318 , R01 AG19771 , RC2 AG036535 , P30 AG10133-18S1 , U01 AG032984 ), Indiana Economic Development Corporation ( IEDC # 87884 ), and from Siemens Medical Solutions and Welch Allyn, Inc .Informed consent was obtained from all ADNI participants according to the Helsinki Declaration and necessary approval was received from Ethical Committees at each of the participating research institutions. Further information about ADNI can be found in ( Jack et al., 2008a; Mueller et al., 2005; Petersen et al., 2010a ) and at www.adni-info.org .
PY - 2010/8
Y1 - 2010/8
N2 - Atrophic changes in early Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) have been proposed as biomarkers for detection and monitoring. We analyzed magnetic resonance imaging (MRI) atrophy rate from baseline to 1 year in 4 groups of participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI): AD (n = 152), converters from MCI to probable AD (MCI-C, n = 60), stable MCI (MCI-S, n = 261), and healthy controls (HC, n = 200). Scans were analyzed using multiple methods, including voxel-based morphometry (VBM), regions of interest (ROIs), and automated parcellation, permitting comparison of annual percent change (APC) in neurodegeneration markers. Effect sizes and the sample required to detect 25% reduction in atrophy rates were calculated. The influence of APOE genotype on APC was also evaluated. AD patients and converters from MCI to probable AD demonstrated high atrophy APCs across regions compared with minimal change in healthy controls. Stable MCI subjects showed intermediate atrophy rates. APOE genotype was associated with APC in key regions. In sum, APC rates are influenced by APOE genotype, imminent MCI to AD conversion, and AD-related neurodegeneration.
AB - Atrophic changes in early Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) have been proposed as biomarkers for detection and monitoring. We analyzed magnetic resonance imaging (MRI) atrophy rate from baseline to 1 year in 4 groups of participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI): AD (n = 152), converters from MCI to probable AD (MCI-C, n = 60), stable MCI (MCI-S, n = 261), and healthy controls (HC, n = 200). Scans were analyzed using multiple methods, including voxel-based morphometry (VBM), regions of interest (ROIs), and automated parcellation, permitting comparison of annual percent change (APC) in neurodegeneration markers. Effect sizes and the sample required to detect 25% reduction in atrophy rates were calculated. The influence of APOE genotype on APC was also evaluated. AD patients and converters from MCI to probable AD demonstrated high atrophy APCs across regions compared with minimal change in healthy controls. Stable MCI subjects showed intermediate atrophy rates. APOE genotype was associated with APC in key regions. In sum, APC rates are influenced by APOE genotype, imminent MCI to AD conversion, and AD-related neurodegeneration.
KW - Alzheimer's Disease Neuroimaging Initiative (ADNI)
KW - Apolipoprotein E (APOE) epsilon 4 allele
KW - Genetic factors
KW - Hippocampus
KW - Longitudinal change
KW - Magnetic resonance imaging (MRI)
KW - Mild cognitive impairment (MCI)
KW - Voxel-based morphometry (VBM)
UR - http://www.scopus.com/inward/record.url?scp=77953998854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953998854&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2010.04.029
DO - 10.1016/j.neurobiolaging.2010.04.029
M3 - Article
C2 - 20620664
AN - SCOPUS:77953998854
VL - 31
SP - 1401
EP - 1418
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 8
ER -