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Title: Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer's disease
Authors: Vipin A. 
Loke Y.M. 
Liu S. 
Hilal S. 
Shim H.Y. 
Xu X. 
Tan B.Y. 
Venketasubramanian N. 
Chen C.L.-H. 
Zhou J. 
Keywords: aged
Alzheimer disease
brain region
cerebrovascular disease
controlled study
default mode network
disease severity
executive function
functional connectivity
functional disease
image analysis
major clinical study
memory disorder
mild cognitive impairment
neuropsychological test
nuclear magnetic resonance imaging
priority journal
Alzheimer disease
biological model
brain mapping
cerebrovascular disease
chi square distribution
cognitive defect
diagnostic imaging
image processing
mental health
middle aged
nerve tract
very elderly
Aged, 80 and over
Alzheimer Disease
Brain Mapping
Cerebrovascular Disorders
Chi-Square Distribution
Cognitive Dysfunction
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Mental Status Schedule
Middle Aged
Models, Neurological
Neural Pathways
Neuropsychological Tests
Issue Date: 2018
Publisher: BioMed Central Ltd.
Citation: Vipin A., Loke Y.M., Liu S., Hilal S., Shim H.Y., Xu X., Tan B.Y., Venketasubramanian N., Chen C.L.-H., Zhou J. (2018). Cerebrovascular disease influences functional and structural network connectivity in patients with amnestic mild cognitive impairment and Alzheimer's disease. Alzheimer's Research and Therapy 10 (1) : 82. ScholarBank@NUS Repository.
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. © 2018 The Author(s).
Source Title: Alzheimer's Research and Therapy
ISSN: 17589193
DOI: 10.1186/s13195-018-0413-8
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