Abstract
Objective: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. Methods: APOE ε4 allele frequency, CSF proteins (Aβ1-42, total tau, hyperphosphorylated tau [p-tau181p]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 ± 0.4 years). Results: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p ≤ 0.02). In addition, the CSF ratio p-tau181p/Aβ1-42 (β = 1.10 ± 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline. Conclusions: Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau181p/Aβ1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 230-238 |
| Number of pages | 9 |
| Journal | Neurology |
| Volume | 75 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 20 2010 |
ASJC Scopus subject areas
- Clinical Neurology
Access to Document
Other files and links
Fingerprint Dive into the research topics of 'Comparing predictors of conversion and decline in mild cognitive impairment'. Together they form a unique fingerprint.
Cite this
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
Comparing predictors of conversion and decline in mild cognitive impairment. / Landau, S. M.; Harvey, D.; Madison, C. M.; Reiman, E. M.; Foster, N. L.; Aisen, P. S.; Petersen, R. C.; Shaw, L. M.; Trojanowski, J. Q.; Jack, C. R.; Weiner, M. W.; Jagust, W. J.
In: Neurology, Vol. 75, No. 3, 20.07.2010, p. 230-238.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Comparing predictors of conversion and decline in mild cognitive impairment
AU - Landau, S. M.
AU - Harvey, D.
AU - Madison, C. M.
AU - Reiman, E. M.
AU - Foster, N. L.
AU - Aisen, P. S.
AU - Petersen, R. C.
AU - Shaw, L. M.
AU - Trojanowski, J. Q.
AU - Jack, C. R.
AU - Weiner, M. W.
AU - Jagust, W. J.
N1 - Funding Information: Dr. Landau receives research support from the NIH (U01 AG024904 [Research Specialist]). Dr. Harvey serves as an Associate Editor of Statistics for Alzheimer Disease and Associated Disorders; and receives research support from the NIH (NIA 2P30AG10129 [Biostatistician], NIA R01AG029672 [Biostatistician], NIA 1U01AG24904 [Member of Biostatistics Core], NRCC RL1NS062412 [Biostatistician], NIA R01AG031252 [Biostatistician], 1RC2AG036535-01 [Member of Biostatistics Team]) and from the Hillblom Foundation. Dr. Madison reports no disclosures. Dr. Reiman serves on scientific advisory boards for Accera, Inc., AstraZeneca, Elan Corporation, Eli Lilly and Company, and GlaxoSmithKline; serves as a consultant to Amnestix/Sygnis; serves as Deputy Editor of the Journal of Clinical Psychiatry; holds a patent re: Methods for Tracking the Progression of Alzheimer's Disease Identifying Treatment Using Transgenic Mice and has patents pending re: Evaluation Of Treatment To Decrease The Risk Of Progressive Brain Disorder Or Slow Brain Aging, Methodologies Linking Patterns From Multi-Modality Datasets, and Methods of Diagnosing Alzheimer's Disease and Associated Genetic Markers; and receives research support from Kronos Life Sciences, GlaxoSmithKline, AstraZeneca, Avid Radiopharmaceuticals, Inc., the NIH (NIA 9 R01 AG031581-10 [PI]), and from the State of Arizona. Dr. Foster serves/has served on scientific advisory boards for Myriad Pharmaceuticals, GE Healthcare, Wyeth/Elan Corporation, the National Alliance for Caregiving, the University of Texas Southwestern Alzheimer's Disease Research Center, the University of Alabama at Birmingham Alzheimer's Disease Research Center, and the NIH Alzheimer's Disease Neuroimaging Initiative (ADNI); has received speaker honoraria from Myriad Pharmaceuticals and GE Healthcare; receives research support from Eli Lilly and Company, Baxter Bioscience/ADCS, Elan Corporation, Merck & Co., Inc., Myriad Genetics, Eisai Inc./ICON Medical Research; the NIH (NIA U01 AG024904 [Site PI], R01 EB00768 [Co-I], U01 AG10483 [Site Co-I], NIA R01 AG022394 [PI], NINDS T32 NS07222 [Co-I]), CMS, the University of Pennsylvania, the Donald W. Reynolds Foundation, and from the Ben B. and Iris M. Margolis Foundation. Dr. Aisen serves on a scientific advisory board for NeuroPhage; serves as a consultant to Elan Corporation, Wyeth, Eisai Inc., Neurochem Inc., Schering-Plough Corp., Bristol-Myers Squibb, Eli Lilly and Company, NeuroPhage, Merck & Co., Roche, Amgen, Genentech, Inc., Abbott, Pfizer Inc, Novartis, and Medivation, Inc.; receives research support from Pfizer Inc, Baxter International Inc., Neuro-Hitech, Abbott, Martek, and the NIH (NIA U01-AG10483 [PI], NIA U01-AG024904 [Coordinating Center Director], NIA R01-AG030048 [PI], and R01-AG16381 [Co-I]); and has received stock options from Medivation, Inc. and NeuroPhage. Dr. Petersen serves on scientific advisory boards for Elan Corporation, Wyeth, and GE Healthcare; receives royalties from the publication of Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH/NIA (U01 AG 06786 [PI], P50 AG 16574 [PI], U01 AG 024904 [Subcontract PI], and R01 AG11378 [Co-I]). Dr. Shaw has received funding for travel and speaker honoraria from Pfizer Inc; serves on the editorial board of Therapeutic Drug Monitoring; may potentially receive revenue for patent pending (application number 10/192,193): O-methylated rapamycin derivatives for alleviation and inhibition of lymphoproliferative disorders, licensed by the University of Pennsylvania to Novartis; receives royalties from publication of Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring (Wolters Kluwer/Lippincott Williams & Wilkins, 2005); receives research support from the NIH (AG024904 [Co-PI Biomarker Core Laboratory]); and receives board of directors' compensation and holds stock options in Saladax Biomedical. Dr. Trojanowski has received funding for travel and honoraria from Takeda Pharmaceutical Company Ltd. and to attend numerous conferences not funded by industry; serves as an Associate Editor of Alzheimer's & Dementia; may accrue revenue on patents re: Modified Avidin-Biotin Technique, Method of Stabilizing Microtubules to Treat Alzheimer's Disease, Method of Detecting Abnormally Phosphorylated Tau, Method of Screening for Alzheimer's Disease or Disease Associated with the Accumulation of Paired Helical Filaments, Compositions and Methods for Producing and Using Homogeneous Neuronal Cell Transplants, Rat Comprising Straight Filaments in Its Brain, Compositions and Methods for Producing and Using Homogeneous Neuronal Cell Transplants to Treat Neurodegenerative Disorders and Brain and Spinal Cord Injuries, Diagnostic Methods for Alzheimer's Disease by Detection of Multiple MRNAs, Methods and Compositions for Determining Lipid Peroxidation Levels in Oxidant Stress Syndromes and Diseases, Compositions and Methods for Producing and Using Homogenous Neuronal Cell Transplants, Method of Identifying, Diagnosing and Treating Alpha-synuclein Positive Neurodegenerative Disorders, Mutation-specific Functional Impairments in Distinct Tau Isoforms of Hereditary Frontotemporal Dementia and Parkinsonism Linked to Chromosome-17: Genotype Predicts Phenotype, Microtubule Stabilizing Therapies for Neurodegenerative Disorders; and Treatment of Alzheimer's and Related Diseases with an Antibody; and receives research support from the NIH (NIA P01 AG 09215-20 [PI], NIA P30 AG 10124-18 [PI], NIA PO1 AG 17586-10 [Project 4 Leader], NIA 1PO1 AG-19724-07 [Core C Leader], NIA 1 U01 AG 024904-05 [Co-PI Biomarker Core Laboratory], NINDS P50 NS053488-02 [PI], NIA UO1 AG029213-01 (Co-I); RC2NS069368 (PI), RC1AG035427 (PI), and NIA P30AG036468 [PI]), and from the Marian S. Ware Alzheimer Program. Dr. Jack serves as a consultant for Eli Lilly and Company and Elan Corporation; is an investigator in clinical trials sponsored by Baxter International Inc., Pfizer Inc, the NIH/NIA (AG11378 [PI], P50-AG16574 [Co-I], and U01 AG024904-01 [Co-I], and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation; 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 Nestlé and Kenes International and to attend conferences not funded by industry; serves on the editorial board of Alzheimer's & Dementia; 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., the NIH (U01AG024904 [PI], P41 RR023953 [PI], R01 AG10897 [PI], P01AG19724 [Co-I], P50AG23501 [Co-I], R24 RR021992 [Co-I], R01 NS031966 [Co-I], and P01AG012435 [Co-I]), the US Department of Defense (DAMD17-01-1-0764 [PI]), the Veterans Administration (MIRECC VISN 21 [Core PI]), and from the State of California; and holds stock in Synarc and Elan Corporation. Dr. Jagust has served on a scientific advisory board for Genentech, Inc.; has served as a consultant for Synarc, Elan Corporation, Genentech, Inc., Ceregene, Schering-Plough Corp., and Merck & Co; and receives research support from the NIH (AG027859 [PI], AG027984 [PI], and AG 024904 [Co-I]) and from the Alzheimer's Association. Funding Information: In this study, we used MCI participant data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a multicenter project with approximately 50 medical center and university sites across the United States and Canada. ADNI is supported by the NIH, private pharmaceutical companies, and nonprofit organizations, and has the primary goal of evaluating MRI, PET, CSF, and clinical measures acquired serially over 2–3 years. Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH Grant U01 AG024904) . ADNI is funded by the National Institute on Aging, by the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, Inc., 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 and K01 AG030514 and the Dana Foundation.
PY - 2010/7/20
Y1 - 2010/7/20
N2 - Objective: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. Methods: APOE ε4 allele frequency, CSF proteins (Aβ1-42, total tau, hyperphosphorylated tau [p-tau181p]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 ± 0.4 years). Results: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p ≤ 0.02). In addition, the CSF ratio p-tau181p/Aβ1-42 (β = 1.10 ± 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline. Conclusions: Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau181p/Aβ1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.
AB - Objective: A variety of measurements have been individually linked to decline in mild cognitive impairment (MCI), but the identification of optimal markers for predicting disease progression remains unresolved. The goal of this study was to evaluate the prognostic ability of genetic, CSF, neuroimaging, and cognitive measurements obtained in the same participants. Methods: APOE ε4 allele frequency, CSF proteins (Aβ1-42, total tau, hyperphosphorylated tau [p-tau181p]), glucose metabolism (FDG-PET), hippocampal volume, and episodic memory performance were evaluated at baseline in patients with amnestic MCI (n = 85), using data from a large multisite study (Alzheimer's Disease Neuroimaging Initiative). Patients were classified as normal or abnormal on each predictor variable based on externally derived cutoffs, and then variables were evaluated as predictors of subsequent conversion to Alzheimer disease (AD) and cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subscale) during a variable follow-up period (1.9 ± 0.4 years). Results: Patients with MCI converted to AD at an annual rate of 17.2%. Subjects with MCI who had abnormal results on both FDG-PET and episodic memory were 11.7 times more likely to convert to AD than subjects who had normal results on both measures (p ≤ 0.02). In addition, the CSF ratio p-tau181p/Aβ1-42 (β = 1.10 ± 0.53; p = 0.04) and, marginally, FDG-PET predicted cognitive decline. Conclusions: Baseline FDG-PET and episodic memory predict conversion to AD, whereas p-tau181p/Aβ1-42 and, marginally, FDG-PET predict longitudinal cognitive decline. Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention.
UR - http://www.scopus.com/inward/record.url?scp=77954981027&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954981027&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e3181e8e8b8
DO - 10.1212/WNL.0b013e3181e8e8b8
M3 - Article
C2 - 20592257
AN - SCOPUS:77954981027
VL - 75
SP - 230
EP - 238
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 3
ER -