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Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer’s disease

Iturria-Medina, Yasser ; Carbonell, Félix M. ; Sotero, Roberto C. ; Chouinard-Decorte, Francois ; Evans, Alan C.

NeuroImage (Orlando, Fla.), 2017-05, Vol.152, p.60-77 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer’s disease
Autor: Iturria-Medina, Yasser ; Carbonell, Félix M. ; Sotero, Roberto C. ; Chouinard-Decorte, Francois ; Evans, Alan C.
Assuntos: Aged ; Alzheimer Disease - diagnostic imaging ; Alzheimer Disease - pathology ; Alzheimer Disease - physiopathology ; Alzheimer Disease - therapy ; Alzheimer's disease ; Atrophy ; Binding energy ; Bioindicators ; Biomarkers ; Blood flow ; Blood-brain barrier ; Brain ; Brain - blood supply ; Brain - diagnostic imaging ; Brain - pathology ; Brain - physiopathology ; Brain architecture ; Brain mapping ; Brain Mapping - methods ; Cerebral blood flow ; Chemical compounds ; Circuits ; Cognitive ability ; Computational neuroscience ; Computational therapeutic design ; Computer applications ; Control theory ; Control theory of networks ; Controllability ; Data processing ; Dementia disorders ; Disease Progression ; Ethics ; Female ; Functional magnetic resonance imaging ; Glucose ; Glucose - metabolism ; Hippocampus ; Homogeneity ; Humans ; Impact prediction ; Intervention ; Intra-brain pathological spreading ; Male ; Metabolism ; Models, Neurological ; Multifactorial causal model ; Multimodal direct interactions ; Neural networks ; Neural Pathways - blood supply ; Neural Pathways - diagnostic imaging ; Neural Pathways - metabolism ; Neural Pathways - pathology ; Neurodegeneration ; Neuroimaging ; Neurotoxicity ; Proteins ; Ranking ; Signal Processing, Computer-Assisted ; Signal transduction ; Statistical analysis ; Stimulation ; Sustainable development ; Triggering pathological event ; Vascular system ; β-Amyloid
É parte de: NeuroImage (Orlando, Fla.), 2017-05, Vol.152, p.60-77
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Descrição: Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer’s disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional strategies. [Display omitted] •A multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention is proposed.•Prediction of complex multifactorial alterations in Alzheimer’s disease, using six different neuroimaging modalities and the MCM.•Identification of potential triggering pathological events and associated “epicenter” brain regions.•Identification and characterization of direct multifactorial interactions, vulnerability, and influence level of each biological factor.•Identification of optimum therapeutic strategies to stop/reverse disease.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer’s disease

Iturria-Medina, Yasser ; Carbonell, Félix M. ; Sotero, Roberto C. ; Chouinard-Decorte, Francois ; Evans, Alan C.

United States: Elsevier Inc

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