Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease |
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| Institution: | 1. Department of Neurology, Layton Aging and Alzheimer''s Disease Center, Oregon Health & Science University, Portland, OR;2. Department of Neurology, University of Michigan, Ann Arbor, MI;3. Michigan Alzheimer''s Disease Center, University of Michigan, Ann Arbor, MI;4. Department of Biostatistics, University of Michigan, Ann Arbor, MI;5. Department of Public Health Sciences, University of California, Davis, CA;6. Portland Veteran Affairs Medical Center, Portland, OR;7. Department of Radiology, University of Michigan, Ann Arbor, MI;8. Neurology Service and Geriatric Research, Education and Clinical Center, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI;1. Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany;2. Department of Psychiatry, University of Patras, Rion Patras, Greece;3. Department of Nuclear Medicine, Technische Universität München, Munich, Germany;4. Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany;5. Biomedical Image Analysis Group, Department of Computing, Imperial College London, UK;6. Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece;7. Neuroepidemiology and Ageing Research Unit, School of Public Health, The Imperial College of Science, Technology and Medicine, London, UK;8. West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK;9. Department of Nuclear Medicine, University of Cologne, Cologne, Germany;10. Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Mainz, Germany;1. LC Campbell Cognitive Neurology Research Unit, Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Canada;2. Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre (SHSC), Toronto, Canada;3. Institute of Medical Science, University of Toronto (UT), Toronto, Canada;4. Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada;5. Department of Medicine, Neurology, SHSC and UT, Toronto, Canada;1. Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA;2. Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego, CA, USA;3. Department of Neurosciences, University of California, San Diego, CA, USA;1. Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK;2. West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK;3. Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany |
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| Abstract: | BackgroundIt is unknown which commonly used Alzheimer disease (AD) biomarker values—baseline or progression—best predict longitudinal cognitive decline.Methods526 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.ResultsAbout 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.ConclusionsFor 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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| Keywords: | ADNI Cognitive declines Biomarker Biomarker progressions ADNI-mem ADNI-exe MCI FDG-PET MRI volume |
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