Hiroko H Dodge1, Jian Zhu2, Danielle Harvey3, Naomi Saito3, Lisa C Silbert4, Jeffrey A Kaye4, Robert A Koeppe5, Roger L Albin6. 1. Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, OR; Department of Neurology, University of Michigan, Ann Arbor, MI; Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, MI. Electronic address: dodgeh@ohsu.edu. 2. Department of Biostatistics, University of Michigan, Ann Arbor, MI. 3. Department of Public Health Sciences, University of California, Davis, CA. 4. Department of Neurology, Layton Aging and Alzheimer's Disease Center, Oregon Health & Science University, Portland, OR; Portland Veteran Affairs Medical Center, Portland, OR. 5. Department of Radiology, University of Michigan, Ann Arbor, MI. 6. Department of Neurology, University of Michigan, Ann Arbor, MI; Michigan Alzheimer's Disease Center, University of Michigan, Ann Arbor, MI; Neurology Service and Geriatric Research, Education and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.
Abstract
BACKGROUND: It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline. METHODS: 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. RESULTS: About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. CONCLUSIONS: For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers.
BACKGROUND: It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline. METHODS: 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. RESULTS: About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairmentpatients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among ADpatients. CONCLUSIONS: For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers.
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