• Esther M C van Leijsen, van Uden Ingeborg W M IWM Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medic, Mayra I Bergkamp, Helena M van der Holst, David G Norris, Claassen Jurgen A H R JAHR Department of Geriatric Medicine, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud Univer, Kessels Roy P C RPC Department of Medical Psychology, Radboud university medical centre, Radboud Alzheimer Centre, Nijmegen, the Netherlands; Radboud University, Donders , Frank-Erik de Leeuw, and Anil M Tuladhar.
• Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands.
• Neuroimage Clin. 2019 Jan 1; 24: 102048.

AbstractCerebral small vessel disease (SVD) is considered the most important vascular contributor to the development of cognitive impairment and dementia. There is increasing awareness that SVD exerts its clinical effects by disrupting white matter connections, predominantly disrupting connections between rich club nodes, a set of highly connected and interconnected regions. Here we examined the progression of disturbances in rich club organization in older adults with SVD and their associations with conventional SVD markers and cognitive decline. We additionally investigated associations of baseline network measures with dementia. In 270 participants of the RUN DMC study, we performed diffusion tensor imaging (DTI) and cognitive assessments longitudinally. Rich club organization was examined in structural networks derived from DTI followed by deterministic tractography. Global efficiency (p<0.05) and strength of rich club connections (p<0.001) declined during follow-up. Decline in strength of peripheral connections was associated with a decline in overall cognition (β=0.164; p<0.01), psychomotor speed (β=0.151; p<0.05) and executive function (β=0.117; p<0.05). Baseline network measures were reduced in participants with dementia, and the association between WMH and dementia was causally mediated by global efficiency (p = =0.037) and peripheral connection strength (p = =0.040). SVD-related disturbances in rich club organization progressed over time, predominantly in participants with severe SVD. In this study, we found no specific role of rich club connectivity disruption in causing cognitive decline or dementia. The effect of WMH on dementia was mediated by global network efficiency and the strength of peripheral connections, suggesting an important role for network disruption in causing cognitive decline and dementia in older adults with SVD.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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