Assessing inter-modal and inter-regional dependencies in prodromal Alzheimer's disease using multimodal MRI/PET and Gaussian graphical models
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Several neuroimaging markers have been established for the early diagnosis of Alzheimer's disease, among them amyloid-beta deposition, glucose metabolism, and gray matter volume. Up to now, these imaging modalities were mostly analyzed separately from each other, and little is known about the regional interrelation and dependency of these markers. Gaussian graphical models (GGMs) are able to estimate the conditional dependency between many individual random variables. We applied GGMs for studying the inter-regional associations and dependencies between multimodal imaging markers in prodromal Alzheimer's disease. Data from N=667 subjects with mild cognitive impairment, dementia, and cognitively healthy controls were obtained from the ADNI. Mean amyloid load, glucose metabolism, and gray matter volume was calculated for each brain region. GGMs were estimated using a Bayesian framework and for each individual diagnosis, graph-theoretical statistics were calculated to determine structural changes associated with disease severity. Highly inter-correlated regions, e.g. adjacent regions in the same lobes, formed distinct clusters but included only regions within the same imaging modality. Hardly any associations were found between different modalities, indicating almost no conditional dependency of brain regions across modalities when considering the covariance explained by all other regions. Network measures clustering coefficient and path length were significantly altered across diagnostic groups, with a biphasic u-shape trajectory. GGMs showed almost no conditional dependencies between modalities when at the same time considering various other regions within the same modalities. However, this approach could be used as a clustering method to derive graph statistics in future studies omitting the need to binarize the network as currently being done for connections based on Pearson correlation.
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