Diverging Progression of Network Disruption and Atrophy in Alzheimer's Disease and Semantic Dementia

Abstract

The progression of cognitive deficits in Alzheimer's disease and semantic dementia is accompanied by grey matter atrophy and white matter deterioration. The impact of neuronal loss on the structural network connectivity in these dementia subtypes is, however, not well understood. In order to gain a more refined knowledge of the topological organization of white matter alterations in dementia, we used a network-based approach to analyze the brain's structural connectivity network. Diffusion-weighted and anatomical MRI images of groups with eighteen Alzheimer's disease and six semantic dementia patients, as well as twenty-one healthy controls were recorded to reconstruct individual connectivity networks. Additionally, voxel-based morphometry, using grey and white matter volume, served to relate atrophy to altered structural connectivity. The analyses showed that Alzheimer's disease is characterized by decreased connectivity strength in various cortical regions. An overlap with grey matter loss was found only in the inferior frontal and superior temporal areas. In semantic dementia, significantly reduced network strength was found in the temporal lobes, which converged with grey and white matter atrophy. Therefore, this study demonstrated that the structural disconnection in early Alzheimer's disease goes beyond grey matter atrophy and is independent of white matter volume loss, an observation that was not found in semantic dementia.

Keywords: Alzheimer’s disease; atrophy; diffusion magnetic resonance; frontotemporal dementia; structural connectivity.

Fig.1

Orange shaded areas visualize grey matter volume reductions (p < 0.05 family-wise error rate corrected) of Alzheimer’s disease and semantic dementia groups compared to healthy controls. S, superior; P, posterior; L, left; I, inferior; A, anterior; R, right.

Fig.2

Boxplots of the global network metrics for healthy control (HC), Alzheimer’s disease (AD), and semantic dementia (SD) groups. Metrics were computed based on networks with ACN weighting scheme and a connectivity threshold of 2000.

Fig.3

Visualization of the local differences in the cortical networks of healthy controls versus Alzheimer’s disease (top row) and healthy controls versus semantic dementia (bottom row). Colored nodes indicate significant differences in connectivity strength (green nodes), grey matter volume (blue nodes, significant difference in at least 50 voxels and >1% of the region), or both (red nodes).