Wang L, Schultz A, Dickerson BC, Becker JA, Johnson KA, Sperling RA.
Amyloid deposition disrupts local coupling of intrinsic brain activity in cognitively normal elderly.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background: Amyloid-s deposition has been associated with disruption of large-scale intrinsic functional
connectivity in cognitively normal older individuals.
Objective: To determine whether local coherence within nodes of the default network is related to amyloid-s
deposition and disruption in long-range connectivity.
Methods: Forty-two cognitively normal older participants were scanned with resting-state functional magnetic
resonance imaging (fMRI), and 11C Pittsburgh Compound B (PiB) PET. Amyloid burden was estimated by calculating
mean cortical PiB retention, and was analyzed as both continuous and dichotomous variable (PiB+ = DVR > 1.15).
Local coherence was measured by computing Kendallfs coefficient of concordance between fMRI time course of
a given voxel and time courses of that voxelfs nearest neighboring voxels (number of neighboring voxels = 26),
reflecting the internal homogeneity of regional intrinsic activity. Local coherence was assessed at the voxel-wise
map level and in a priori regions-of-interest (ROIs), including posterior cingulate cortex (PCC), inferior parietal
lobules (IPL), medial prefrontal cortex (MPFC) and hippocampus. Long-range connectivity was estimated with a
summary measure of the inter-regional correlation between the same set of ROIs as above.
Results: Map level analyses revealed that increasing amyloid burden was related to decreased local coherence
in the PCC, MPFC, and IPL. This finding remained significant when analyses were restricted to grey matter
voxels within cortical ribbon to account for potential effects of atrophy. ROI analyses revealed that high amyloid
burden disrupted both local coherence in the PCC and long-range connectivity across the default network
nodes. Furthermore, 36% of variance in long-range default network connectivity was explained by the PCC local
Conclusions: These findings suggest that amyloid-related disruption of local coherence, particularly in the PCC,
may prove to be a sensitive indicator of early regional dysfunction, and may account for much of the observed
abnormality in long-range default network connectivity among amyloid-positive cognitively normal elderly.