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Dementia risk factors modify hubs but leave other connectivity measures unchanged in asymptomatic individuals: a graph theoretical analysis

Clarke, Hannah, Messaritaki, Eirini ORCID:, Dimitriadis, Stavros ORCID: and Metzler-Baddeley, Claudia ORCID: 2022. Dementia risk factors modify hubs but leave other connectivity measures unchanged in asymptomatic individuals: a graph theoretical analysis. Brain Connectivity 12 (1) , pp. 26-40. 10.1089/brain.2020.0935

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Background: Alzheimer's Disease (AD) is the most common form of dementia with genetic and environmental risk contributing to its development. Graph theoretical analyses of brain networks constructed from structural and functional MRI measurements have identified connectivity changes in AD and individuals with mild cognitive impairment (MCI). However, brain connectivity in asymptomatic individuals at risk of AD remains poorly understood. Methods: We acquired diffusion-weighted magnetic resonance imaging (dMRI) data from 160 asymptomatic individuals (38-71 years) from the Cardiff Ageing and Risk of Dementia Study (CARDS). We calculated white matter tracts and constructed whole-brain, default-mode-network and visual structural brain networks that incorporate multiple structural metrics as edge weights. We then calculated the relationship of three AD risk factors, namely Apolipoprotein-E ε4 genotype (APOE4), family history (FH) of dementia, and central obesity, on graph theoretical measures and hubs. Results: We observed no risk-related differences in clustering coefficients, characteristic path lengths, eccentricity, diameter and radius across the whole-brain, default-mode-network or visual system. However, a hub in the right paracentral lobule was present in all high-risk groups (FH, APOE4, obese) but absent in low-risk groups (no FH, APOE4-ve, healthy weight). Discussion: We identified no risk-related effects on graph theoretical metrics in the structural brain networks of cognitively healthy individuals. However, high-risk was associated with a hub in the right paracentral lobule, an area with motor and sensory functions related to the lower limb. If this phenotype is shown to predict symptom development in longitudinal studies, it could be used as an early biomarker of AD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information: This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (
Publisher: Mary Ann Liebert
ISSN: 2158-0014
Funders: Wellcome Trust
Date of First Compliant Deposit: 10 August 2021
Date of Acceptance: 23 May 2021
Last Modified: 15 May 2023 23:43

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