Objective:To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment.Methods:A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested.Results:Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed.Conclusions:Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies.
In stable nonhypoxemic COPD there is reduced white matter integrity throughout the brain and widespread disturbance in functional activation of gray matter, which may contribute to cognitive dysfunction. White matter microstructural integrity but not gray matter functional activation is independent of smoking and cerebrovascular comorbidity. The mechanisms remain unclear, but may include cerebral small vessel disease caused by COPD.
ObjectivesLacunes are an important disease feature of cerebral small vessel disease (SVD) but their relationship to cognitive impairment is not fully understood. To investigate this we determined (1) the relationship between lacune count and total lacune volume with cognition, (2) the spatial distribution of lacunes and the cognitive impact of lacune location, and (3) the whole brain anatomical covariance associated with these strategically located regions of lacune damage.MethodsOne hundred and twenty one patients with symptomatic lacunar stroke and radiological leukoaraiosis were recruited and multimodal MRI and neuropsychological data acquired. Lacunes were mapped semi-automatically and their volume calculated. Lacune location was automatically determined by projection onto atlases, including an atlas which segments the thalamus based on its connectivity to the cortex. Lacune locations were correlated with neuropsychological results. Voxel based morphometry was used to create anatomical covariance maps for these ‘strategic’ regions.ResultsLacune number and lacune volume were positively associated with worse executive function (number p < 0.001; volume p < 0.001) and processing speed (number p < 0.001; volume p < 0.001). Thalamic lacunes, particularly those in regions with connectivity to the prefrontal cortex, were associated with impaired processing speed (Bonferroni corrected p = 0.016). Regions of associated anatomical covariance included the medial prefrontal, orbitofrontal, anterior insular cortex and the striatum.ConclusionLacunes are important predictors of cognitive impairment in SVD. We highlight the importance of spatial distribution, particularly of anteromedial thalamic lacunes which are associated with impaired information processing speed and may mediate cognitive impairment via disruption of connectivity to the prefrontal cortex.
C erebral ischemic small vessel disease (SVD) is associated with stroke and cognitive impairment. Magnetic resonance imaging (MRI) characteristics of SVD include lacunar infarcts, T2 hyperintensities (leukoaraiosis), and cerebral microbleeds (CMBs).1,2 CMBs are signal voids on T2*-weighted gradient echo MRI, resulting from paramagnetic properties of focal deposits of hemosiderin-containing macrophages, 3 ranging in diameter between 0.82 and 1.5 mm. 4 CMB incidence is up to 80% in patients with subcortical vascular dementia.5 They are also common in the monogenic form of SVD, cerebral autosomal-dominant angiopathy with subcortical infarcts and leukoencephalopathy. 6 SVD is associated with a characteristic cognitive impairment, with prominent impaired executive function and information processing speed, but relatively preserved episodic memory. 7 The correlation of cognition with T2-lesion load is weak, 8 but stronger correlations have been detected with diffusion tensor imaging (DTI). 9 The association between DTI and cognition has been regarded as support for SVD causing cognitive impairment via white matter tract disruption causing a disconnection syndrome. Associations have also been reported between cognition and both brain atrophy 9 and lacunar infarct count. 10 Recent studies suggest CMBs play a role in cognitive impairment, although results have been inconsistent. CMB frequency increases with age, reported in 17.8% of those aged 60 to 69 years and 38.3% of those aged 80 to 99 years.2 Healthy adults with CMBs showed a reduction in the attention and calculation section of the Mini-Mental State Examination (MMSE) 11,12 and information processing and motor speed. 13 In elderly normal subjects, CMBs were associated with cognitive impairment and dementia. 13 This relationship was weakened, but still significant, Background and Purpose-Cerebral microbleeds (CMBs) are common in cerebral small vessel disease. They may cause cognitive impairment, possibly via white matter tract disruption but previous studies have produced inconsistent results. We determined whether CMB number and location are associated with impaired cognition in symptomatic small vessel disease and whether any association was independent of other magnetic resonance imaging markers of small vessel disease. Methods-One hundred sixteen patients with lacunar stroke and radiological leukoaraiosis were studied. Neuropsychological assessment was performed. CMBs on gradient echo images were assessed using the Brain Observer Microbleed Rating Scale criteria. Magnetic resonance imaging measures, including diffusion tensor imaging, were also analyzed. Associations between cognitive function and the presence, number, and location of CMBs were determined. Results-CMBs were present in 46 (39.7%) patients. CMB number correlated weakly with executive function (r=0.22; P=0.022) but not with other cognitive indices. CMBs count in the top decile (≥9 CMB, N=12) was more strongly associated with poor executive function; this association remained significant ...
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