scholarly journals Longitudinal relation between structural network efficiency, cognition, and gait in cerebral small vessel disease

2021 ◽  
Author(s):  
Mengfei Cai ◽  
Mina A Jacob ◽  
David G Norris ◽  
Frank-Erik de Leeuw ◽  
Anil M Tuladhar
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Network Efficiency ◽  
Gait Performance ◽  
Vessel Disease ◽  
Conventional Mri ◽  
Global Efficiency ◽  
Structural Network ◽  
Over Time

Abstract Background To investigate changes in gait performance over time and how these changes are associated with the decline in structural network efficiency and cognition in older patients with cerebral small vessel disease (SVD). Methods In a prospective, single-center cohort with 217 older participants with SVD, we performed 1.5T MRI scans, cognitive tests and gait assessments evaluated by Timed UP and Go (TUG) test twice over 4 years. We reconstructed the white matter network for each subject based on diffusion tensor imaging tractography, followed by graph-theoretical analyses to compute the global efficiency. Conventional MRI markers for SVD, i.e., white matter hyperintensity (WMH) volume, number of lacunes and microbleeds, were assessed. Results Baseline global efficiency was not related to changes in gait performance, while decline in global efficiency over time was significantly associated with gait decline (i.e., increase in TUG time), independent of conventional MRI markers for SVD. Neither baseline cognitive performance nor cognitive decline was associated with gait decline. Conclusions We found that disruption of the white matter structural network was associated with gait decline over time, while the effect of cognitive decline was not. This suggests that structural network disruption has an important role in explaining the pathophysiology of gait decline in older patients with SVD, independent of cognitive decline.

scholarly journals Longitudinal decline in structural networks predicts dementia in cerebral small vessel disease

Neurology ◽  
2018 ◽  
Vol 90 (21) ◽  
pp. e1898-e1910 ◽  
Author(s):  
Andrew J. Lawrence ◽  
Eva A. Zeestraten ◽  
Philip Benjamin ◽  
Christian P. Lambert ◽  
Robin G. Morris ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Conventional Mri ◽  
Global Efficiency ◽  
Structural Network ◽  
Structural Networks ◽  
Network Disruption

ObjectiveTo determine whether longitudinal change in white matter structural network integrity predicts dementia and future cognitive decline in cerebral small vessel disease (SVD). To investigate whether network disruption has a causal role in cognitive decline and mediates the association between conventional MRI markers of SVD with both cognitive decline and dementia.MethodsIn the prospective longitudinal SCANS (St George's Cognition and Neuroimaging in Stroke) Study, 97 dementia-free individuals with symptomatic lacunar stroke were followed with annual MRI for 3 years and annual cognitive assessment for 5 years. Conversion to dementia was recorded. Structural networks were constructed from diffusion tractography using a longitudinal registration pipeline, and network global efficiency was calculated. Linear mixed-effects regression was used to assess change over time.ResultsSeventeen individuals (17.5%) converted to dementia, and significant decline in global cognition occurred (p = 0.0016). Structural network measures declined over the 3-year MRI follow-up, but the degree of change varied markedly between individuals. The degree of reductions in network global efficiency was associated with conversion to dementia (B = −2.35, odds ratio = 0.095, p = 0.00056). Change in network global efficiency mediated much of the association of conventional MRI markers of SVD with cognitive decline and progression to dementia.ConclusionsNetwork disruption has a central role in the pathogenesis of cognitive decline and dementia in SVD. It may be a useful disease marker to identify that subgroup of patients with SVD who progress to dementia.

scholarly journals Structural network changes in cerebral small vessel disease

2019 ◽  
Vol 91 (2) ◽  
pp. 196-203 ◽  
Author(s):  
Anil M Tuladhar ◽  
Jonathan Tay ◽  
Esther van Leijsen ◽  
Andrew J Lawrence ◽  
Ingeborg Wilhelmina Maria van Uden ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Psychomotor Speed ◽  
Network Efficiency ◽  
Vessel Disease ◽  
Global Efficiency ◽  
Structural Network ◽  
Imaging Markers

ObjectivesTo investigate whether longitudinal structural network efficiency is associated with cognitive decline and whether baseline network efficiency predicts mortality in cerebral small vessel disease (SVD).MethodsA prospective, single-centre cohort consisting of 277 non-demented individuals with SVD was conducted. In 2011 and 2015, all participants were scanned with MRI and underwent neuropsychological assessment. We computed network properties using graph theory from probabilistic tractography and calculated changes in psychomotor speed and overall cognitive index. Multiple linear regressions were performed, while adjusting for potential confounders. We divided the group into mild-to-moderate white matter hyperintensities (WMH) and severe WMH group based on median split on WMH volume.ResultsThe decline in global efficiency was significantly associated with a decline in psychomotor speed in the group with severe WMH (β=0.18, p=0.03) and a trend with change in cognitive index (β=0.14, p=0.068), which diminished after adjusting for imaging markers for SVD. Baseline global efficiency was associated with all-cause mortality (HR per decrease of 1 SD 0.43, 95% CI 0.23 to 0.80, p=0.008, C-statistic 0.76).ConclusionDisruption of the network efficiency, a metric assessing the efficiency of network information transfer, plays an important role in explaining cognitive decline in SVD, which was however not independent of imaging markers of SVD. Furthermore, baseline network efficiency predicts risk of mortality in SVD that may reflect the global health status of the brain in SVD. This emphasises the importance of structural network analysis in the context of SVD research and the use of network measures as surrogate markers in research setting.

scholarly journals Structural network efficiency predicts cognitive decline in cerebral small vessel disease

2020 ◽  
Vol 27 ◽  
pp. 102325
Author(s):  
Esther M. Boot ◽  
Esther MC van Leijsen ◽  
Mayra I. Bergkamp ◽  
Roy P.C. Kessels ◽  
David G. Norris ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Network Efficiency ◽  
Vessel Disease ◽  
Structural Network

scholarly journals Cognitive consequences of regression of cerebral small vessel disease

2018 ◽  
Vol 4 (1) ◽  
pp. 85-89 ◽  
Author(s):  
Esther MC van Leijsen ◽  
Mayra I Bergkamp ◽  
Ingeborg WM van Uden ◽  
Sjacky Cooijmans ◽  
Mohsen Ghafoorian ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Vessel Disease ◽  
Disease Markers ◽  
Total Brain

Introduction Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Patients and methods Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Results Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Discussion Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Conclusion Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.

scholarly journals Blood–brain barrier leakage at baseline and cognitive decline in cerebral small vessel disease: a 2-year follow-up study

GeroScience ◽  
2021 ◽  
Author(s):  
Danielle Kerkhofs ◽  
Sau May Wong ◽  
Eleana Zhang ◽  
Renske Uiterwijk ◽  
Erik I. Hoff ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
Blood Brain Barrier ◽  
Grey Matter ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Brain Barrier ◽  
Vessel Disease

AbstractBlood–brain barrier (BBB) dysfunction is one of the pathophysiological mechanisms in cerebral small vessel disease (SVD). Previously, it was shown that BBB leakage volume is larger in patients with SVD compared with controls. In this study, we investigated the link between BBB leakage and cognitive decline over 2 years in patients with cSVD. At baseline, 51 patients with clinically overt cSVD (lacunar stroke or mild vascular cognitive impairment) received a dynamic contrast-enhanced MRI scan to quantify BBB permeability in the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical grey matter (CGM), and deep grey matter (DGM). Cognitive function in the domain executive function, information processing speed, and memory was measured in all patients at baseline and after 2 years. The association between baseline BBB leakage and cognitive decline over 2 years was determined with multivariable linear regression analysis, corrected for age, sex, educational level, baseline WMH volume, and baseline brain volume. Regression analyses showed that higher baseline leakage volume and rate in the NAWM and CGM were significantly associated with increased overall cognitive decline. Furthermore, higher baseline leakage volume in the NAWM and CGM, and higher baseline leakage rate in the CGM were significantly associated with increased decline in executive function. This longitudinal study showed that higher BBB leakage at baseline is associated with stronger cognitive decline, specifically in executive function, over 2 years of follow-up in patients with cSVD. These results emphasize the key role of BBB disruption in the pathophysiology and clinical progression of cSVD.

scholarly journals Cognition mediates the relation between structural network efficiency and gait in small vessel disease

2021 ◽  
Vol 30 ◽  
pp. 102667
Author(s):  
Mengfei Cai ◽  
Mina A. Jacob ◽  
David G. Norris ◽  
Marco Duering ◽  
Frank-Erik de Leeuw ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Small Vessel ◽  
Network Efficiency ◽  
Vessel Disease ◽  
Structural Network

scholarly journals Structural network efficiency is associated with cognitive impairment in small-vessel disease

Neurology ◽  
2014 ◽  
Vol 83 (4) ◽  
pp. 304-311 ◽  
Author(s):  
A. J. Lawrence ◽  
A. W. Chung ◽  
R. G. Morris ◽  
H. S. Markus ◽  
T. R. Barrick
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Small Vessel ◽  
Network Efficiency ◽  
Vessel Disease ◽  
Structural Network

scholarly journals Vascular cognitive impairment in the mouse reshapes visual, spatial network functional connectivity

2020 ◽  
Author(s):  
Gerard R Hall ◽  
Philipp Boehm-Sturm ◽  
Ulrich Dirnagl ◽  
Carsten Finke ◽  
Marco Foddis ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Small Vessel Disease ◽  
Vascular Cognitive Impairment ◽  
Network Activity ◽  
Small Vessel ◽  
Vessel Disease ◽  
Visual Spatial ◽  
Structural Connectome ◽  
Global Efficiency

AbstractConnectome analysis of neuroimaging data is a rapidly expanding field to identify disease specific biomarkers. Structural diffusion MRI connectivity has been useful in individuals with radiological features of small vessel disease, such as white matter hyperintensities. Global efficiency, a network metric calculated from the structural connectome, is an excellent predictor of cognitive decline. To dissect the biological underpinning of these changes, animal models are required. We tested whether the structural connectome is altered in a mouse model of vascular cognitive impairment. White matter damage was more pronounced by 6 compared to 3 months. Global efficiency remained intact, but the visual association cortex exhibited increased structural connectivity with other brain regions. Exploratory resting state functional MRI connectivity analysis revealed diminished default mode network activity in the model compared to shams. Further perturbations were observed in a primarily cortical hub and the retrosplenial and visual cortices, and the hippocampus were the most affected nodes. Behavioural deficits were observed in the cued water maze, supporting the suggestion that the visual and spatial memory networks are affected. We demonstrate specific circuitry is rendered vulnerable to vascular stress in the mouse, and the model will be useful to examine pathophysiological mechanisms of small vessel disease.Graphical abstract

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