Vemuri P, Jones DT, Machulda M, Przybelski SA, Boeve BF, Knopman DS, Petersen RC, Jack Jr CR.
Functional reorganization of the brain along the Alzheimer's disease continuum.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Background: We investigated changes in functional connectivity (FC) in subjects along the Alzheimer's disease
(AD) continuum from dementia to cognitively normal (CN) using resting-state fMRI. We assume that amyloid
deposition occurs early in the disease process. We used the previous established global cortical PIB threshold
of 1.5 to classify subjects as negative or positive and defined the different stages of the AD continuum as: PIBnegative
CN (CNN) (n = 123), PIB-positive CN (CNP) (n = 52); PIB-positive mild cognitive impaired subjects (MCIP)
(n = 25) and AD (n = 48).
Methods and results: Applying graph theory methods on seed-to-seed FC among 2997 nodes placed throughout
the cerebral gray matter, we found significant increases in global FC in CNP compared to CNN. This increase in
global FC in CNP declined monotonically as subjects moved from CNP to MCIP and AD. In addition, we also
performed network level analysis by computing seed-to-seed FC among 143 seeds placed in 27 major networks
(these were detected in 341 CN elderly subjects using an ICA analysis). This analysis was done to understand how
the FC changes between and within each of the major networks contribute to the observed global FC changes.
In CNP, we found only significant between network FC increases but not within network FC changes. In AD, we
found significant within network as well as between network FC decreases suggesting a systematic network level
decline in FC. Also, we found that the network most affected by disease was the Ventral DMN.
Conclusions: These results suggest significant functional reorganization along the AD continuum. Increased FC
in CNP is consistent with functional reorganization in CN subjects with a significant amyloid load who are able to
compensate. Progressive loss of FC in MCIP and AD subjects suggests that these subjects are no longer able to
compensate for the effects of progressively more severe disease.