Journal
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
Volume 2, Issue 10, Pages -Publisher
WILEY
DOI: 10.1038/psp.2013.54
Keywords
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Categories
Funding
- ADNI (National Institutes of Health) [U01 AG024904]
- National Institute on Aging (NIA)
- National Institute of Biomedical Imaging and Bioengineering (NIBIB)
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Bio-Clinica
- Biogen Idec
- Bristol-Myers Squibb Company
- Eisai
- Elan Pharmaceuticals
- Eli Lilly and Company
- F Hoffmann-La Roche
- Genentech
- GE Healthcare
- Innogenetics NV
- IXICO
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace
- Merck Co.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer
- Piramal Imaging
- Servier
- Synarc
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- NIH [P30AG010129, K01 AG030514]
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Disease-onset time (DOT) and disease trajectory concepts were applied to derive an Alzheimer's disease (AD) progression population model using the clinical dementia rating scale-sum of boxes (CDR-SOB) from the AD neuroimaging initiative (ADNI) database. The model enabled the estimation of a DOT and a disease trajectory for each patient. The model also allowed distinguishing fast and slow-progressing subpopulations according to the functional assessment questionnaire, normalized hippocampal volume, and CDR-SOB score at study entry. On the basis of these prognostic factors, 81% of the mild cognitive impairment (MCI) subjects could correctly be assigned to slow or fast progressers, and 77% of MCI to AD conversions could be predicted whereas the model described correctly 84% of the conversions. Finally, synchronization of the biomarker-time profiles on estimated individual DOT virtually expanded the population observation period from 3 to 8 years. DOT-disease trajectory model is a powerful approach that could be applied to many progressive diseases.
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