Sepulcre J, Becker A, Hedden T, Sperling R, Buckner L, Johnson K.
Hubs of atrophy and amyloid-s in AD and normal aging.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background: Neurodegenerative diseases such as Alzheimer's disease (AD) are thought to affect large systems
in the brain where pathology spreads along particular networks rather than randomly appearing in unrelated
regions. Although critical advances have been made in order to understand dementia neuropathology, networks
and mechanisms of pathologic spread remain largely unknown.
Methods: We used structural MRI and PET-PIB imaging to characterize hubs of atrophy and amyloid in elderly
(PIB-, N = 25; and PIB+, N = 25) and AD dementia (N = 25). We first obtained the specific networks for each modality
and clinical condition using the group volume or PIB intensity variability, applying degree centrality to quantify the
number of links or edges connected to each node. Correlation coefficients were computed in the ith row and jth
column of adjacency matrices to obtain the links of the final graphs. Additionally, we used a seed-based approach
and diffusion of information algorithms to isolate sub-networks and analyze diffusion patterns of atrophy and
amyloid across the brain.
Results: We identified four top hub regions in both neuroimaging modalities: hippocampus/parahipocampus
formation (HPHF), posterior cingulate (PCC), prefrontal midline and lateral prefrontal. Seed placement in the medial
temporal lobe revealed three main pathways: (1) one anterior path, from HPHF to orbitofrontal regions, (2) one
posterior path, from HPHF to PCC and (3) one lateral path, from HPHF to temporolateral regions. At later stages
of information diffusion, there are another three important pathways: (1) from PCC to prefrontal midline, (2) from
PCC to temporolateral regions and (3) from PCC to lateral prefrontal regions. Finally, at latest stages, we detected
covariance in atrophy and amyloid in the lateral prefrontal subnetworks.
Conclusions: These results suggest that AD is a network gcommunityh disease engaging well-defined systems of
interconnected neurons at the short and large-scale and that amyloid deposition is associated with atrophy across
specific brain networks.