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- W2897472303 abstract "The heterogeneity and complexity of Alzheimer's disease (AD) lends itself to dynamic causal modeling (DCM), a computational systems biology approach to simulate complex systems. We implemented a DCM to test the current descriptive model of biomarker evolution in AD (Jack et al., 2013)(1). We modeled biomarkers (e.g. amyloid, tau and neurodegeneration) and cognitive impairment as first order non-linear differential equations to include amyloid dependent and non-dependent neurodegenerative cascades. We tested the DCM models using several simulation scenarios (amyloid first, comorbidities, etc) to determine whether computed biomarker trajectories agreed with those of the theoretical model. We also simulated the effects of anti-amyloid therapy early and late in the course of AD. The first DCM of early-onset “pure AD” closely matched that of the model of Jack et al., 2013. Specifically, the early onset AD model demonstrated the initial appearance of amyloid, followed by other biomarkers of tau and neurodegeneration, followed by the onset of cognitive decline depending on parameters related to cognitive reserve. Similarly, the late-onset AD models demonstrated the first appearance of amyloid or neurodegeneration, depending on a parameter related to the magnitude of age-related comorbid pathology, and also closely matched the model. Simulation of anti-amyloid therapy early in the disease demonstrated delayed onset of cognitive changes in the early AD biomarker model but little or none in others. Finally we will present plots to show personalized trajectories of individual at risk patients derived from the Alzheimer's Disease Neuroimaging Initiative database to depict how such modeling can be eventually extended to AD precision medicine. Dynamic causal modeling may be useful to better dissect the heterogeneity of AD biomarker evolution, implement and test descriptive models, and develop precision medicine strategies for diagnosis and treatment. Reference: 1. Jack CR, Jr., Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron. 2013;80(6):1347-58" @default.
- W2897472303 created "2018-10-26" @default.
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- W2897472303 date "2018-07-01" @default.
- W2897472303 modified "2023-10-16" @default.
- W2897472303 title "IC‐04‐01: A PRECISION MEDICINE APPROACH TO MODELING BIOMARKERS IN EARLY AND LATE ONSET ALZHEIMER'S DISEASE" @default.
- W2897472303 doi "https://doi.org/10.1016/j.jalz.2018.06.2049" @default.
- W2897472303 hasPublicationYear "2018" @default.
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