P4‐375: Alzheimer's disease and mild cognitive impairment weaken connections within the default‐mode network: A multimodal study with resting‐state fMRI, diffusion MRI and FDG‐PET

Abstract

A multi-modal imaging approach was applied to understand alterations in the default-mode network from normal aging to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants included 10 probable AD, 11 amnestic MCI, and 12 age and education-matched normal control (NC) subjects. Whole-brain resting-state functional, diffusion tensor and volumetric MRI as well as FDG-PET data were acquired. Cognitive assessment on all subjects included St. Louis University test of Mental Status (SLUMS) and Wechsler Memory Scale III Logical Memory delayed recall (LM-dr) test. With the right and left isthmi of cingulate cortex (ICCs) as seed regions, functional correlation and fiber tracking connectivity distribution to all other voxels of the brain were calculated. Between-group t tests were carried. Correlation analyses were obtained between the functional connectivity of default-mode network components and (1) pons-normalized PET signal, (2) cortical thickness/volume and (3) cognitive performance. Whole-brain group analyses showed significant functional connectivity differences (NC > AD) from the right and left ICCs to medial frontal gyrus /anterior cingulate cortex and surrounding regions. There was a general trend of NC > MCI > AD on both functional and structural connectivity from the right and left ICCs to these frontal regions (Fig. 1). Significant correlations were found between PET signal in the right and left ICCs, right and left hippocampi and left ICC-right hippocampus functional connectivity (Table 1, Fig. 2). Significant correlations between PET signal and cortical thickness/volume were also found (Table 1). Significant correlations were found between the left ICC-right hippocampus functional connectivity and SLUMS score (r = 0.459, p = 0.0082) as well as LM-dr score (r = 0.375, p = 0.0347). There is a clear reduction of structural and functional connectivity within the default-mode network in AD, consistent with the reduction of metabolic activity and cortical atrophy in this network. The multi-modal correlation analyses suggest that neuronal damage in the left ICC is associated with declines in metabolic activity in this region, functional connectivity to this region and cognitive performance. Overall, the default-mode network continues to serve as a key region to understanding brain alterations due to AD. The integrated visualization of the functional and structural connections for normal, MCI and AD subjects (left to right) with the seed regions at the (a) right isthmus of cingulate cortex (ICC), (b) left ICC and (c) left lateral occipital cortex (LOC) and associated white matter regions. Thresholds: The mean correlation of > 0.2 for functional connectivity and mean connectivity distribution of > 1000 for structural connectivity. Green: functional connection only. Orange: structural connection only. Red: coexistence of both connections. GM: gray matter. WM: white matter. R = right. L = left. MeFG = medial frontal gyrus. With all subjects included, the significant correlations were shown between the left ICC-right hippocampus functional connection (the Fisher's Z-transformed values of the correlations) and the normalized PET signals in (a) left ICC and (b) right hippocampus. R = right, L = left and ICC= isthmus of cingulate cortex.