Dataset Information

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

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 (?=0.164; p<0.01), psychomotor speed (?=0.151; p<0.05) and executive function (?=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.

SUBMITTER: van Leijsen EMC

PROVIDER: S-EPMC6978216 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

van Leijsen Esther M C EMC van Uden Ingeborg W M IWM Bergkamp Mayra I MI van der Holst Helena M HM Norris David G DG Claassen Jurgen A H R JAHR Kessels Roy P C RPC de Leeuw Frank-Erik FE Tuladhar Anil M AM

NeuroImage. Clinical 20191022

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 co ...[more]

PMID: 31706220

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Project description:Background Carotid artery stiffness is associated with cognitive impairment and dementia, but the underlying mechanisms remain unknown. We examined the associations of carotid artery stiffness with cerebral small-vessel disease markers, cognition, and dementia subtypes in a memory clinic cohort. Methods and Results A total of 272 participants underwent carotid ultrasonography, 3 Tesla brain magnetic resonance imaging, and neuropsychological assessment. Carotid ultrasonography was used to assess β-index, pressure-strain elastic modulus, and pulse-wave velocity-β. Brain magnetic resonance images were graded for cerebral small-vessel disease markers, including white matter hyperintensities, lacunes, and cerebral microbleeds. Participants were classified as having no cognitive impairment, cognitive impairment and no dementia, or dementia subtyped as Alzheimer disease and vascular dementia. Cognition was assessed using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network harmonization battery. After adjusting for age, sex, cardiovascular risk factors, and diseases, multivariable models showed that β-index (β=0.69; P=0.002), elastic modulus (β=0.78; P<0.001), and pulse-wave velocity-β (β=0.80; P<0.001) were associated with white matter hyperintensities, and elastic modulus (odds ratio [OR], 1.39 [95% CI, 1.04-1.85]) and pulse-wave velocity-β (OR, 1.47 [95% CI, 1.10-1.98]) were independently associated with lacunes. Similarly, β-index (OR, 2.04 [95% CI, 1.14-4.13]), elastic modulus (OR, 2.22 [95% CI, 1.25-4.42]), and pulse-wave velocity-β (OR, 2.50 [95% CI, 1.36-5.18]) were independently associated with vascular dementia. Carotid stiffness measures were independently associated with worse performance in global cognition, visuomotor speed, visuospatial function, and executive function. These associations became largely nonsignificant after further adjusting for cerebral small-vessel disease markers. Conclusions In memory clinic patients, carotid artery stiffness was associated with white matter hyperintensities and lacunes, impairment in global and domain-specific cognition, and causative subtypes of dementia, particularly vascular. The effects of carotid stiffness on cognition were not independent of, and were partially mediated by, cerebral small-vessel disease.

Project description:Graph-theoretical analysis of brain connectivity data has revealed significant features of brain network organization across a range of species. Consistently, large-scale anatomical networks exhibit highly nonrandom attributes including an efficient small world modular architecture, with distinct network communities that are interlinked by hub regions. The functional importance of hubs motivates a closer examination of their mutual interconnections, specifically to examine the hypothesis that hub regions are more densely linked than expected based on their degree alone, i.e. forming a central rich club. Extending recent findings of rich club topology in the cat and human brain, this report presents evidence for the existence of rich club organization in the cerebral cortex of a non-human primate, the macaque monkey, based on a connectivity data set representing a collation of numerous tract tracing studies. Rich club regions comprise portions of prefrontal, parietal, temporal and insular cortex and are widely distributed across network communities. An analysis of network motifs reveals that rich club regions tend to form star-like configurations, indicative of their central embedding within sets of nodes. In addition, rich club nodes and edges participate in a large number of short paths across the network, and thus contribute disproportionately to global communication. As rich club regions tend to attract and disperse communication paths, many of the paths follow a characteristic pattern of first increasing and then decreasing node degree. Finally, the existence of non-reciprocal projections imposes a net directional flow of paths into and out of the rich club, with some regions preferentially attracting and others dispersing signals. Overall, the demonstration of rich club organization in a non-human primate contributes to our understanding of the network principles underlying neural connectivity in the mammalian brain, and further supports the hypothesis that rich club regions and connections have a central role in global brain communication.

Project description:Objectives: Endothelial dysfunction (ED) has been linked to the pathogenesis of cerebral small vessel disease (SVD). We aimed to assess ED and cerebrovascular reactivity (CVR) in the patients with a diverse manifestation of SVD, with similar and extensive white matter lesions (WMLs, modified Fazekas scale grade ≥2), compared with a control group (CG) without the MRI markers of SVD, matched for age, gender, hypertension, diabetes, and to evaluate the change of CVR following 24 months. Methods: We repeatedly measured the vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery (MCA) by the transcranial Doppler ultrasound (TCD) techniques in 60 subjects above 60 years with a history of lacunar stroke (LS), vascular dementia (VaD), or parkinsonism (VaP) (20 in each group), and in 20 individuals from a CG. Results: The mean age, frequency of the main vascular risk factors, and sex distribution were similar in the patients with the SVD groups and a CG. The VMRr and the BHI were more severely impaired at baseline (respectively, 56.7 ± 18% and 0.82 ± 0.39) and at follow-up (respectively, 52.3 ± 16.7% and 0.71 ± 0.38) in the patients with SVD regardless of the clinical manifestations (ANOVA, p > 0.1) than in the CG (respectively, baseline VMRr 77.2 ± 15.6%, BHI 1.15 ± 0.47, p < 0.001; follow-up VMRr 74.3 ± 17.6%, BHI 1.11 ± 0.4, p < 0.001). All the assessed CVR measures (VMRr and BHI) significantly decreased over time in the subjects with SVD (Wilcoxon's signed-rank test p = 0.01), but this was not observed in the CG (p > 0.1) and the decrease of CVR measures was not related to the SVD radiological progression (p > 0.1). Conclusions: This study provided evidence that the change in CVR measures is detectable over a 24-month period in patients with different clinical manifestations of SVD. Compared with the patients in CG with similar atherothrombotic risk factors, all the CVR measures (BMRr and BHI) significantly declined over time in the subjects with SVD. The reduction in CVR was not related to the SVD radiological progression.

Project description:Background and Objective: Studies on relations between arterial stiffness and full spectrum of radiological features of cerebral small vessel disease (CSVD) are scarce. We aim to investigate the association of arterial stiffness with lacunes, white matter hyperintensities (WMH), microbleeds (CMBs), dilated perivascular spaces (PVS), and brain atrophy in a community-based sample. Methods: A total of 953 participants (55.7 ± 9.4 years) who underwent brachial-ankle pulse wave velocity (baPWV) and brain magnetic resonance imaging were included. Lacunes, CMBs, and PVS were visually rated. Brain structure and WMH were automatically segmented. Brain parenchyma fraction (BPF), a surrogate index of brain atrophy, was calculated as a ratio of brain parenchyma volume to total intracranial volume. Multivariable logistic and linear regressions were used to investigate the associations between baPWV and CSVD. Subsequently, we explored these associations in strata of age. Results: Increased baPWV was associated with severe PVS in white matter (OR, 1.09; 95%CI, 1.01-1.17; p = 0.022), larger WMH volume (?, 0.08; 95%CI, 0.04-0.12; p < 0.001), lower BPF (?, -0.09; 95%CI, -0.15- -0.03; p = 0.007), and marginally associated with strictly lobar CMBs (OR, 1.11; 95%CI, 1.00-1.23; p = 0.055), but not with lacunes. WMH volume mediated the relation between baPWV and BPF. In age subgroup analysis, the association of baPWV with PVS in white matter was stronger among those aged <55 years, whereas the association with brain atrophy was more prominent among those aged ?55 years. Increased baPWV was associated with larger WMH volume in both younger and older individuals. Conclusions: Increased arterial stiffness was associated with most of imaging markers of CSVD, including PVS in white matter, larger WMH volume, strictly lobar CMBs, and brain atrophy, but not lacunes. The mechanisms underlying these associations and their potential clinical significances warrant further investigations.

Dataset Information

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

Publications

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

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