Longitudinal changes in rich club organization and cognition in cerebral small vessel disease

Esther M C van Leijsen; Ingeborg W M van Uden; Mayra I Bergkamp; Helena M van der Holst; David G Norris; Jurgen A H R Claassen; Roy P C Kessels; Frank-Erik de Leeuw; Anil M Tuladhar

doi:10.1016/j.nicl.2019.102048

Longitudinal changes in rich club organization and cognition in cerebral small vessel disease

Neuroimage Clin. 2019:24:102048. doi: 10.1016/j.nicl.2019.102048. Epub 2019 Oct 22.

Authors

Esther M C van Leijsen¹, Ingeborg W M van Uden¹, Mayra I Bergkamp¹, Helena M van der Holst², David G Norris³, Jurgen A H R Claassen⁴, Roy P C Kessels⁵, Frank-Erik de Leeuw¹, Anil M Tuladhar⁶

Affiliations

¹ Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands.
² Department of Neurology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, the Netherlands.
³ Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, the Netherlands; Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany.
⁴ Department of Geriatric Medicine, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Radboud Alzheimer Centre, Nijmegen, the Netherlands.
⁵ Department of Medical Psychology, Radboud university medical centre, Radboud Alzheimer Centre, Nijmegen, the Netherlands; Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognition, Nijmegen, the Netherlands.
⁶ Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Anil.Tuladhar@radboudumc.nl.

Abstract

Cerebral 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.

Keywords: Cerebral small vessel disease; Cognitive decline; Dementia; Diffusion tensor imaging; Rich club organization; Structural neuroimaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Brain / diagnostic imaging*
Cerebral Small Vessel Diseases / diagnostic imaging*
Cerebral Small Vessel Diseases / psychology
Cognition / physiology*
Cognitive Dysfunction / diagnostic imaging*
Cognitive Dysfunction / psychology
Diffusion Tensor Imaging
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neuropsychological Tests
Reaction Time / physiology
White Matter / diagnostic imaging*