Publication Type Academic Article
Authors Raj A, Kuceyeski A, Weiner M
Journal Neuron
Volume 73
Issue 6
Pagination 1204-15
Date Published 03/21/2012
ISSN 1097-4199
Keywords Brain, Brain Mapping, Dementia, Disease Progression, Models, Neurological
Abstract Patterns of dementia are known to fall into dissociated but dispersed brain networks, suggesting that the disease is transmitted along neuronal pathways rather than by proximity. This view is supported by neuropathological evidence for "prion-like" transsynaptic transmission of disease agents like misfolded tau and beta amyloid. We mathematically model this transmission by a diffusive mechanism mediated by the brain's connectivity network obtained from tractography of 14 healthy-brain MRIs. Subsequent graph theoretic analysis provides a fully quantitative, testable, predictive model of dementia. Specifically, we predict spatially distinct "persistent modes," which, we found, recapitulate known patterns of dementia and match recent reports of selectively vulnerable dissociated brain networks. Model predictions also closely match T1-weighted MRI volumetrics of 18 Alzheimer's and 18 frontotemporal dementia subjects. Prevalence rates predicted by the model strongly agree with published data. This work has many important implications, including dimensionality reduction, differential diagnosis, and especially prediction of future atrophy using baseline MRI morphometrics.
DOI 10.1016/j.neuron.2011.12.040
PubMed ID 22445347
PubMed Central ID PMC3623298
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