Alterations in functional vs. metabolic networks in Alzheimer’s disease

Objectives Functional magnetic resonance imaging (fMRI) studies found disruption of resting state networks (RSNs) such as default mode network (DMN) in Alzheimer’s disease (AD). While application of fMRI in clinical settings is still very limited, PET with [18F]-fluorodeoxyglucose (FDG-PET) is a well-established tool assisting diagnosis of dementing disorders. Recent studies reported that RSNs can be successfully captured also with FDG-PET. Here, we examined AD-related alterations in functional and metabolic RSNs using fMRI and FDG-PET, respectively.

Methods Thirty eight patients with mild AD dementia and 22 healthy subjects (HS) underwent a simultaneous resting state fMRI/FDG-PET session on a hybrid PET/MR system. RSNs were identified using independent component analysis. Individual integrity of functional RSNs was examined using a goodness-of-fit (beta-weights) relative to established functional templates. To examine individual integrity of metabolic RSNs, image data (one image per subject) of patients and HS were pooled within a common ICA. Finally, so-called loading coefficients, a degree to which each individual contributed to a given metabolic RSN, were extracted.

Results A number of known RSNs could be identified in both fMRI and FDG-PET data. Preliminary results indicate significantly reduced integrity of the DMN in AD patients relative to HS in both imaging modalities. However, a larger effect size was found in metabolic then in functional data (Image). As expected, no difference between the groups was noted for the sensorimotor network, likewise in both imaging modalities.

Conclusions In line with the literature, we found disrupted functional connectivity of the DMN in AD. As a novel finding, the network's alteration was even more pronounced in terms of metabolic connectivity. Connectivity modeling of FDG-PET data might be valuable in diagnosis of dementing disorders. Investigation of other RSNs is under way.

Research Support Igor Yakushev was supported by an internal grant program for resident physicians (KKF, project number B23-13/8764179).