Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network

Abstract

Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative – 50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the ‘rich-club’ – a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich-club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich-club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline.

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

“…In AD dementia, structural connectivity networks exhibit altered topological network metrics, such as increased shortest path lengths, decreased local and global efficiency, and decreased number of rich-club hub nodes (Daianu et al, 2013(Daianu et al, , 2015Lo et al, 2010;Shao et al, 2012). These topological network changes were also shown to account for core memory and executive function deficits (Reijmer et al, 2013), and were already detectable in cognitively normal individuals with high amyloid burden (Fischer, Wolf, Scheurich, & Fellgiebel, 2015) and asymptomatic APOE4 carriers (Brown et al, 2011).…”

Axonal diameter and density estimated with 7-Tesla hybrid diffusion imaging in transgenic Alzheimer rats

“…Measures of axonal density and diameter are important morphological properties of WM, as their integrity is directly related to the rate of information transfer of a nerve bundle and can provide insight into the effects of neurological disease [5], otherwise not detectable with macroscopic neuroimaging metrics. The benefits of HYDI and detailed microscopic indices may be valuable for human [13][14][15][16] and animal connectome (Fig. 3C) projects and clinical research [4,17,18].…”

The Structural and Functional Connectome and Prediction of Risk for Cognitive Impairment in Older Adults

“…It has recently been shown that not all structural core networks are disrupted in AD. Specifically, AD more strongly affected low-degree brain regions rather than the high-degree nodes that form a rich club , leaving this low-degree network better preserved [52]. However, more research is needed to better understand the SC and FC changes in AD and their impact on clinical and cognitive decline.…”