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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2018

Open Access 01-12-2018 | Research

Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer’s disease

Authors: Ashwati Vipin, Yng Miin Loke, Siwei Liu, Saima Hilal, Hee Youn Shim, Xin Xu, Boon Yeow Tan, Narayanaswamy Venketasubramanian, Christopher Li-Hsian Chen, Juan Zhou

Published in: Alzheimer's Research & Therapy | Issue 1/2018

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Abstract

Background

Patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.

Methods

We examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.

Results

We demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.

Conclusions

We demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.
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Metadata
Title
Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer’s disease
Authors
Ashwati Vipin
Yng Miin Loke
Siwei Liu
Saima Hilal
Hee Youn Shim
Xin Xu
Boon Yeow Tan
Narayanaswamy Venketasubramanian
Christopher Li-Hsian Chen
Juan Zhou
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-018-0413-8

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