Structural Insights into Aberrant Topological Patterns of Large-Scale Cortical Networks in Alzheimer's Disease

Abstract

Recent research on Alzheimer's disease (AD) has shown that cognitive and memory decline in this disease is accompanied by disrupted changes in the coordination of large-scale brain functional networks. However, alterations in coordinated patterns of structural brain networks in AD are still poorly understood. Here, we used cortical thickness measurement from magnetic resonance imaging to investigate large-scale structural brain networks in 92 AD patients and 97 normal controls. Brain networks were constructed by thresholding cortical thickness correlation matrices of 54 regions and analyzed using graph theoretical approaches. Compared with controls, AD patients showed decreased cortical thickness intercorrelations between the bilateral parietal regions and increased intercorrelations in several selective regions involving the lateral temporal and parietal cortex as well as the cingulate and medial frontal cortex regions. Specially, AD patients showed abnormal small-world architecture in the structural cortical networks (increased clustering and shortest paths linking individual regions), implying a less optimal topological organization in AD. Moreover, AD patients were associated with reduced nodal centrality predominantly in the temporal and parietal heteromodal association cortex regions and increased nodal centrality in the occipital cortex regions. Finally, the brain networks of AD were about equally as robust to random failures as those of controls, but more vulnerable against targeted attacks, presumably because of the effects of pathological topological organization. Our findings suggest that the coordinated patterns of cortical morphology are widely altered in AD patients, thus providing structural evidence for disrupted integrity in large-scale brain networks that underlie cognition. This work has implications for our understanding of how functional deficits in patients are associated with their underlying structural (morphological) basis.

Power spectral density and coherence analysis of Alzheimer’s EEG

“…Thus, nowadays, several studies about functional networks have been carried out to explore the dysconnectivity of AD from neurophysiological signals (He et al 2009;Joudaki et al 2012;Stam et al 2007, Stam 2010. Recent studies have proposed that AD is characterized by the conversion from small-world network architecture to less optimal functional topologies (SanzArigita et al 1994;He et al 2008;Supekar et al 2008). Our findings also support this idea.…”

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer’s Disease

“…These results resemble past research on functional connectivity strength using graph-based analyses [10,12,13,15]. In these studies, longer path lengths were found in MCI [12] and mild AD [10,13], reflecting disrupted interactions of distant brain regions.…”

“…While earlier studies report altered functional connectivity in AD patients, the precise pattern remains ambiguous, ranging from increased to decreased to no change in global connectivity and lower or no change in local connectivity in AD patients relative to healthy controls (HC) [8][9][10][11][12][13][14][15]. These studies focused on whole brain or predefined regional connectivity.…”

Spontaneous brain activity observed with functional magnetic resonance imaging as a potential biomarker in neuropsychiatric disorders

“…Using the same method as Achard and colleagues (Achard et al 2006), Supekar and colleagues ) have demonstrated that resting-state fMRI-derived functional brain networks in AD show a loss of small-world properties. In contrast to a previous EEG study ) and a structural MRI study (He et al 2008), Supekar and colleagues (2008) found that the loss of small-world properties in AD were characterized by a significantly lower clustering coefficient. This may indicate a disrupted local connectivity, not a significantly longer path length as the earlier two studies reported.…”